Morrison, Dennis R.; Mosier, Benjamin; Cassanto, John
Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.
Křen, Vladimír; Řezanka, Tomáš
Roč. 32, č. 5 (2008), s. 858-889 ISSN 0168-6445 R&D Projects: GA MŠk(CZ) LC06010; GA AV ČR IAA400200503 Institutional research plan: CEZ:AV0Z50200510 Keywords : glycosides * sweet antibiotics * aglycone Subject RIV: CE - Biochemistry Impact factor: 7.963, year: 2008
Evstigneev, M.P.; Rozvadovskaya, A.O.; Kisurkin, D.V.; Dehvis, D.B.; Veselkov, A.N.
The heteroassociation of antitumor antibiotics novotrone (NOV) and actinomycin D (AMD) in aqueous solution has been studied by one- and two-dimensional 1 H-NMR spectroscopy (500 MHz) in order to elucidate the molecular mechanism of the action of antibiotics in combination. It has been shown that heterocomplexes become predominant in the mixed solution at r > 12. It is concluded that aromatic antibiotics (e. g. novotrone and actinomycin D) may form energetically stable heteroassociation complexes in aqueous solution and hence affect their medical-biological activity
Pereira, Florbela; Latino, Diogo A. R. S.; Gaudêncio, Susana P.
The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature. PMID:24473174
N-methylthiolated beta-lactams the name "penicillin" in 1928 after his discovery that molds from the Penicillium genus secrete powerful antimicrobial ...carboxyl grouin close pr ximin to tlhectam l initro’gen, which is required for antimicrobial activity . These antibiotics act as bactericidal agents...AD AWARD NUMBER: W81XWH-04-1-0688 TITLE: Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human
Rodrigo L. Fabri
Full Text Available The bioactivity guided fractionation of the dichloromethane extract of Mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. This compound, hitherto unknown in the genus Mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (HL60, Jurkat and MCF-7 and four Leishmania species. Its identity was confirmed unambiguously by ¹H, 13C, ¹H-COSY, IR and UV-Vis spectroscopy and mass spectrometry. Psychorubrin displayed a very promising antitumor with IC50 of 4.5, 5.6 and 1.1 µM for HL60, Jurkat and MCF-7 cell lines, respectively. Antimicrobial activity, mainly against Cryptococcus neoformans (MIC of 87.3 µM was observed. A pronounced antileishmanial potential was also verified with IC50 varying from 1.7 to 2.7 µM for the Leishmania species tested. This is the first report of the presence of pyranonapthoquinones in the Mitracarpus genus, which may serve as a chemotaxonomical marker.O fracionamento biomonitorado do extrato diclorometânico de Mitracarpus frigidus forneceu a piranonaftoquinona psicorubrina. Essa substância, até então desconhecida no gênero Mitracarpus, teve sua atividade biológica avaliada contra várias bactérias e dois fungos, três linhagens de células tumorais (HL60, Jurkat e MCF-7 e quatro espécies de Leishmania. Sua estrutura foi confirmada por meio de ¹H, 13C, ¹H-COSY, IR e UV-Vis e espectrometria de massas. Psicorubrina exibiu uma atividade antitumoral promissora com CI50 de 4,5, 5,6 e 1,1 µM para HL60, Jurkat e MCF-7, respectivamente. Atividade antimicrobiana, principalmente contra Cryptococcus neoformans (CIM de 87,3 µM, foi observada. Um pronunciado potencial leishmanicida também foi verificado com CI50 variando de 1,7 - 2,7 µM para as diferentes espécies de Leishmania testadas. Este é o primeiro relato da presença de piranonaftoquinonas no gênero Mitracarpus, que poderão ser úteis como marcadores quimiotaxonômicos.
Figure 1. The unreported 15 lead antibiotic MNPs and MbNPs from AntiMarin database, using the best Rfs antibiotic model with a probability of being antibiotic greater than or equal to 0.8. Figure 2. The selected 4 lead antitumor MNPs and MbNPs from the AntiMarin database, using the best Rfs antitumor model with a probability of being antitumor greater than or equal to 0.8. The present work corroborates by one side the results of our previous work6 and enables the presentation of a new set of possible lead like bioactive compounds. Additionally, it is shown the usefulness of quantum-chemical descriptors in the discrimination of biological active and inactive compounds. The use of the εHOMO quantum-chemical descriptor in the discrimination of large scale data sets of lead-like or drug-like compounds has never been reported. This approach results in the reduction, in great extent, of the number of compounds used in real screens, and it reinforces the results of our previous work. Furthermore, besides the virtual screening, the computational methods can be very useful to build appropriate databases, allowing for effective shortcuts of NP extracts dereplication procedures, which will certainly result in increasing the efficiency of drug discovery.
Elshaarawy, Reda F. M.; Eldeen, Ibrahim M.; Hassan, Eman M.
Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens (3a-e) and metallosalophens (4a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 (4f) (IC50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 (4e) (IC50 = 20.30 μg/mL).
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 ...
Coughlin, Jane M; Rudolf, Jeffrey D; Wendt-Pienkowski, Evelyn; Wang, Liyan; Unsin, Claudia; Galm, Ute; Yang, Dong; Tao, Meifeng; Shen, Ben
The bleomycin (BLM) family of glycopeptide-derived antitumor antibiotics consists of BLMs, tallysomycins (TLMs), phleomycins (PLMs), and zorbamycin (ZBM). The self-resistant elements BlmB and TlmB, discovered from the BLM- and TLM-producing organisms Streptomyces verticillus ATCC15003 and Streptoalloteichus hindustanus E465-94 ATCC31158, respectively, are N-acetyltransferases that provide resistance to the producers by disrupting the metal-binding domain of the antibiotics required for activity. Although each member of the BLM family of antibiotics possesses a conserved metal-binding domain, the structural differences between each member, namely, the bithiazole moiety and C-terminal amine of BLMs, have been suggested to instill substrate specificity within BlmB. Here we report that BlmB and TlmB readily accept and acetylate BLMs, TLMs, PLMs, and ZBM in vitro but only in the metal-free forms. Kinetic analysis of BlmB and TlmB reveals there is no strong preference or rate enhancement for specific substrates, indicating that the structural differences between each member of the BLM family play a negligible role in substrate recognition, binding, or catalysis. Intriguingly, the zbm gene cluster from Streptomyces flavoviridis ATCC21892 does not contain an N-acetyltransferase, yet ZBM is readily acetylated by BlmB and TlmB. We subsequently established that S. flavoviridis lacks the homologue of BlmB and TlmB, and ZbmA, the ZBM-binding protein, alone is sufficient to provide ZBM resistance. We further confirmed that BlmB can indeed confer resistance to ZBM in vivo in S. flavoviridis, introduction of which into wild-type S. flavoviridis further increases the level of resistance.
Cooke, H.; Guenther, E; Luo, Y; Shen, B; Bruner, S
The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization.
Hariprasad, Seenu M; Mieler, William F
The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections. © 2016 S. Karger AG, Basel.
Penicillium genus secrete powerful antimicrobial compounds, called beta-lactams (10). X-ray crystallography revealed that penicillin is a thiazolidine...to the beta-lactam ring, a carboxyl group in close proximity to the lactam nitrogen, which is required for antimicrobial activity . These antibiotics... Activity of N-Thiolated B-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors PRINCIPAL INVESTIGATOR: Q. Ping Dou, Ph.D
... Drugs Resources for You Information for Consumers (Drugs) Buying & Using Medicine Safely Antibiotics and Antibiotic Resistance Antibiotics ... Antibiotic Resistance and Protect Public Health The White House Blog FDAâs Take on the Executive Order and ...
Nohara, Toshihiro; Fujiwara, Yukio; El-Aasr, Mona; Ikeda, Tsuyoshi; Ono, Masateru; Nakano, Daisuke; Kinjo, Junei
We examined the sulfides in onion (Allium cepa L.), Welsh onion (A. fistulosum L.), and garlic (A. sativum L.), and obtained three new thiolane-type sulfides (onionins A 1 -A 3 ) from onion; two new thiabicyclic-type sulfides (welsonins A 1 , A 2 ), together with onionins A 1 -A 3 , from Welsh onion; and six new acyclic-type sulfides (garlicnins L-1-L-4, E, and F), ten new thiolane-type sulfides (garlicnins A, B 1 -B 4 , C 1 -C 3 , K 1 , and K 2 ), and three new atypical cyclic-type sulfides (garlicnins G, I, and J) from garlic. Acetone extracts showed the potential of these sulfides in inhibiting the polarization of M2 activated macrophages that are capable of suppressing tumor-cell proliferation. The effect of the thiolane-type sulfide of a major component, onionin A 1 , on tumor progression and metastasis in both osteosarcoma and ovarian cancer-bearing mouse models was then examined. Tumor proliferation was depressed, and tumor metastasis was controlled by regulating macrophage activation. These results showed that onionin A 1 is an effective agent for controlling tumors in both in vitro and in vivo models, and that the antitumor effects observed in vivo are likely caused by reversing the antitumor immune system. Activation of the antitumor immune system by onionin A 1 might be an effective adjuvant therapy for patients with osteosarcoma, ovarian cancer and other malignant tumors. Based on these findings, pharmacological investigations will be conducted in the future to develop natural and healthy foods and anti-cancer agents that can prevent or combat disease.
There is a clear association between antibiotic use and resistance both on individual and population levels. In the European Union, countries with large antibiotic consumption have higher resistance rates. Antibiotic resistance leads to failed treatments, prolonged hospitalisations, increased costs and deaths. With few new antibiotics in the Research & Development pipeline, prudent antibiotic use is the only option to delay the development of resistance. Antibiotic policy consists of prescrib...
... 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 ...
Tang, Gong-Li; Tang, Man-Cheng; Song, Li-Qiang; Zhang, Yue
The tetrahydroisoquinoline (THIQ) alkaloids are naturally occurring antibiotics isolated from a variety of microorganisms and marine invertebrates. This family of natural products exhibit broad spectrum antimicrobial and strong antitumor activities, and the potency of clinical application has been validated by the marketing of ecteinascidin 743 (ET-743) as anticancer drug. In the past 20 years, the biosynthetic gene cluster of six THIQ antibiotics has been characterized including saframycin Mx1 from Myxococcus xanthus, safracin-B from Pseudomonas fluorescens, saframycin A, naphthyridinomycin, and quinocarcin from Streptomyces, as well as ET-743 from Ecteinascidia turbinata. This review gives a brief summary of the current status in understanding the molecular logic for the biosynthesis of these natural products, which provides new insights on the biosynthetic machinery involved in the nonribosomal peptide synthetase system. The proposal of the THIQ biosynthetic pathway not only shows nature's route to generate such complex molecules, but also set the stage to develop a different process for production of ET-743 by synthetic biology.
Pedersen, Inge Kryger; Jepsen, Kim Sune
The medical professions will lose an indispensable tool in clinical practice if even simple infections cannot be cured because antibiotics have lost effectiveness. This article presents results from an exploratory enquiry into “good doctoring” in the case of antibiotic prescribing at a time when...
Pulcini, Céline; Bush, Karen; Craig, William A
In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...
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...... 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....... antibiotic prescribing are a major factor in the prescribing for ARIs. Professional interventions with educational components are effective, although they have modest effects, and are expensive. GPs' perceptions - that mistakenly assume as a default that patients want antibiotics for their ARIs - are often...
... Antibiotics www.healthsci.tufts.edu Georgia-Pacific Health Smart Institute www.gphealthsmart.com Special thanks to Rhonda ... effectiveness of other medications such as birth control pills? 7. Are there any possible adverse reactions if ...
Caimmi, S; Caimmi, D; Lombardi, E; Crisafulli, G; Franceschini, F; Ricci, G; Marseglia, G L
Antibiotics are commonly injected during the perioperative period and are responsible of 15 percent of the anaphylactic reactions. Anaphylaxis triggered by antibiotics primarily involves penicillin and cephalosporin. The management of patients with histories of allergic reactions to antibiotics is a common situation in clinical practice. The confirmation or invalidation of the allergic nature of the reported reaction is not based on in vitro tests, but on a rigorous allergological work-up based on detailed analysis of clinical history, skin tests and drug provocation test. Considering a possible cross-reactivity between penicillins, once an immediate penicillin allergy has been diagnosed, skin testing with the alternative molecule (cephalosporin, carbapenem, aztreonam) is mandatory and, if negative, the relevant drug should be given in an appropriate setting at increasing doses.
Roč. 48, č. 1 (2003), s. 17-25 ISSN 0015-5632 R&D Projects: GA ČR GA204/01/1004 Institutional research plan: CEZ:AV0Z5020903 Keywords : hydrid * antibiotics Subject RIV: EE - Microbiology, Virology Impact factor: 0.857, year: 2003
... in Farm Animals FDA: Cutting-Edge Technology Sheds Light on Antibiotic Resistance For More Information Antibiotics and Antibiotic Resistance Antimicrobial Resistance Information for Consumers and Health Professionals CDC: Get Smart: Know When Antibiotics Work More in Consumer Updates ...
Valdes Iglesias, O; Perez Gil, R; Colom, Y
The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism
Moheno, Phillip B B
A series of in vivo studies are reported that provide evidence for an immunologically mediated mechanism for the antitumor response from a calcium pterin (CaPterin) suspension. Strong antitumor efficacy was demonstrated in fully immunocompetent female C3H/HeN-MTV+ mice (retired breeders) presenting spontaneous mammary gland adenocarcinomas. Comparison of results obtained by testing CaPterin in either nude or SCID mice (severely compromised immunodeficient) implanted with MDA-MB-231 human cancer cells showed a significant antitumor response in the nudes and no response in the SCIDs. This comparison argues for B-cell immunological involvement in the mechanism of CaPterin antitumor activity since nude mice possess B-cell capability while SCID mice do not. This comparison also indicates that there is no measurable direct cancer cell toxicity from the CaPterin. Results showing no CaPterin antitumor efficacy against EMT6 tumor cells implanted in Balb/c mice also suggest an antitumor mechanism involving B-cells, since transforming growth factor beta (TGF-beta), produced by EMT6 cells, is known to cause B-cell apoptosis. Taken together, these results, along with those of other researchers, indicate that CaPterin's antitumor mechanism involves antibody-dependent cellular cytotoxicity (ADCC) mediated, for example, by natural killer (NK) cells, interlukin-2, and CaPterin.
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......Bacteria can avoid extinction during antimicrobial exposure by becoming resistant. They achieve this either via adaptive mutations or horizontally acquired resistance genes. If resistance emerges in clinical relevant species, it can lead to treatment failure and ultimately result in increasing...... 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...
Wright, Gerard D
Rooted in the mechanism of action of antibiotics and subject to bacterial evolution, antibiotic resistance is difficult and perhaps impossible to overcome. Nevertheless, strategies can be used to minimize the emergence and impact of resistance. Antibiotic adjuvants offer one such approach. These are compounds that have little or no antibiotic activity themselves but act to block resistance or otherwise enhance antibiotic action. Antibiotic adjuvants are therefore delivered in combination with antibiotics and can be divided into two groups: Class I agents that act on the pathogen, and Class II agents that act on the host. Adjuvants offer a means to both suppress the emergence of resistance and rescue the activity of existing drugs, offering an orthogonal strategy complimentary to new antibiotic discovery VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available Medermycin and kalafungin, two antibacterial and antitumor antibiotics isolated from different streptomycetes, share an identical polyketide skeleton core. The present study reported the discovery of kalafungin in a medermycin-producing streptomycete strain for the first time. A mutant strain obtained through UV mutagenesis showed a 3-fold increase in the production of this antibiotic, compared to the wild type strain. Heterologous expression experiments suggested that its production was severely controlled by the gene cluster for medermycin biosynthesis. In all, these findings suggested that kalafungin and medermycin could be accumulated by the same streptomycete and share their biosynthetic pathway to some extent in this strain.
Xueqin Ran1, Gen Zhang2, Sheng Li2, Jiafu Wang2,3. 1. College of Animal Science, ... Cite as: Ran X, Zhang G, Li S, Wang J. Characterization and antitumor activity of camptothecin from endophytic fungus Fusarium solani isolated from Camptotheca ... Camptotheca acuminata has been used as tradition- ally Chinese ...
Results: Generally, yellow loosestrife extracts demonstrated antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, S. epidermidis and Streptococcus pyogenes). Strong antitumor activity of yellow loosestrife was observed via potato disc diffusion bioassay. Nine different phenolics were also determined ...
Zhang Zhouen; Nishimoto, S.I.
Tumor hypoxia has been identified as a key subject for tumor therapy, since hypoxic tumor cells show resistance to treatment of tumor tissues by radiotherapy, chemotherapy and phototherapy. For improvement of tumor radiotherapy, we have proposed a series of radiation-activated prodrugs that could selectively release antitumor agent 5-fluorouracil or 5-fluorodeoxyuridine under hypoxic conditions. Recently, we attempted to develop two families of novel hypoxia-targeting antitumor agents, considering that tumor-hypoxic environment is favorable to biological and photochemical reductions. The first family of prodrugs was derived from camptothecin as a potent topoisomerase I inhibitor and several bioreductive motifs. These prodrugs could be activated by NADPH-cytochrome P450 reductase or DT-diaphorase to release free camptothecin, and thereby showed hypoxia-selective cytotoxictiy towards tumor cells. These prodrugs were also applicable to the real-time monitoring of activation and antitumor effect by fluorometry. Furthermore, the camptothecin-bioreductive motif conjugates was confirmed to show an oxygen-independent DAN photocleaving activity, which could overcome a drawback of back electron transfer occurring in the photosensitized one-electron oxidation of DNA. Thus, these camptothecin derivatives could be useful to both chemotherapy and phototherapy for hypoxic tumor cells. The second family of prodrugs harnessed UV light for cancer therapy, incorporating the antitumor agent 5-fluorourcil and the photolabile 2-nitrobenzyl chromophores. The attachment of a tumor-homing cyclic peptide CNGRC was also employed to construct the prototype of tumor-targeting photoactiaved antitumor prodrug. These novel prodrugs released high yield of 5-fluorourcil upon UV irradiation at λ ex =365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)
Qi, Cui-Ling; Wang, Li-Jing; Zhou, Xin-Lei
In recent years, more and more attention was payed to the study of andrographolide. Andrographolide has the extensive pharmacological actions, such as anti-tumor, dephlogisticate and antibiosis and anti-virus. It was dected that andrographolide had the action of anti-tumor in gastric cancer, liver cancer, lung cancer and breast cancer. The anti-tumor mechanism of andrographolide was versatile, for instance, andrographolide can induce the apoptosis of cancer cell, inhibit the cell cycle, and increase the antitumor activity of lymphocyte. The following review was about the recent progress of study on the anti-tumor mechanism of andrographolide.
... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Antibiotic-Resistant Gonorrhea Recommend on Facebook Tweet Share Compartir ... Threat Gonorrhea has progressively developed resistance to the antibiotic drugs prescribed to treat it. Following the spread ...
... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network ...
Full Text Available The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.
The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease
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.
... antibiotic-associated colitis, which can occur after the antibiotic therapy upsets the balance of good and bad bacteria in your intestinal tract. Besides loose stools, C. difficile infection can ... and symptoms of antibiotic-associated diarrhea. These signs and symptoms are common ...
Chen, Yong; Chen, Yayun; Shi, Yeye; Ma, Chengyao; Wang, Xunan; Li, Yue; Miao, Yunjie; Chen, Jianwei; Li, Xiang
Custard apple (Annona squamosa Linn.) is an edible tropical fruit, and its seeds have been used to treat "malignant sore" (cancer) and other usage as insecticide. A comparison of extraction processes, chemical composition analysis and antitumor activity of A. squamosa seed oil (ASO) were investigated. The optimal extraction parameters of ASO were established by comparing percolation, soxhlet, ultrasonic and SFE-CO 2 extraction methods. The chemical composition of fatty acid and content of total annonaceous acetogenins (ACGs) of ASO was investigated by GC-MS and colorimetric assay, and anti-tumor activity of ASO was tested using H 22 xenografts bearing mice. The optimal extraction parameters of ASO were obtained as follows: using soxhlet extraction method with extraction solvent of petroleum ether, temperature of 80°C, and extraction time of 90min. Under these conditions, the yield of ASO was 22.65%. GC-MS analysis results showed that the main chemical compositions of fatty acid of ASO were palmitic acid (9.92%), linoleic acid (20.49%), oleic acid (56.50%) and stearic acid (9.14%). The total ACGs content in ASO was 41.00mg/g. ASO inhibited the growth of H 22 tumor cells in mice with a maximum inhibitory rate of 53.54% by oral administration. Furthermore, it was found that ASO exerted an antitumor effect via decreasing interleukin-6 (IL-6), janus kinase (Jak) and phosphorylated signal transducers and activators of transcription (p-Stat3) expression. The results demonstrated that ASO suppressed the H 22 solid tumor development may due to its main chemical constituents unsaturated fatty acid and ACGs via IL-6/Jak/Stat3 pathway. ASO may be a potential candidate for the treatment of cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Radioimmunotherapy (RIT is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue, and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi-treated MC-38 cells release “danger signals” and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.
Plowman, J; Harrison, S D; Trader, M W; Griswold, D P; Chadwick, M; McComish, M F; Silveira, D M; Zaharko, D
A new antibiotic, deoxyspergualin (DSG), demonstrated antitumor activity against L1210 leukemia in mice. The life span of mice bearing either i.p. or s.c.-implanted L1210 increased greater than 150% following i.p. administration of 25 mg/kg DSG on days 1-9. Activity obtained with i.p. bolus treatments was schedule dependent. The tumor burden in mice bearing the s.c. implanted L1210 was reduced by 4-6 log10 units at the end of treatment when DSG was administered every 3 h for 8 injections on days 1, 5, and 9. By contrast, single injections of DSG on days 1, 5, and 9 allowed the tumor burden to increase at least 100-fold during treatment and daily single injections for 9 days reduced the tumor burden by 2 log10 units. The therapeutic advantage for i.p.-implanted L1210 of maintaining plasma concentrations of DSG was indicated further by infusion studies using s.c.-implanted Alzet osmotic pumps. Tumor burden was reduced by 3.5 and 6 log10 units following s.c. bolus treatments every 3 h on day 1 and a 24 h-infusion, respectively. The optimal infusion time for an infusion rate in mice of 179 mg/kg/day appeared to be 72 h. Pharmacokinetic studies following bolus i.v. injection revealed a rapid plasma clearance of parent drug (20.8 ml/min/kg) and a beta half-life of approximately 12 min. The bolus dose kinetics was used to predict the steady state plasma concentrations resulting from s.c. infusion; good agreement was observed between predicted values and experimental results. Based on these preclinical data, DSG has been developed to clinical trial. Initial Phase I protocols involve a 120-h infusion schedule.
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. © 2016 S. Karger AG, Basel.
Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich
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....
Study of the structure of antibiotics having two or several sugars in their molecule. One may distinguish: the polysaccharide antibiotics themselves, made up of two or several sugars either with or without nitrogen, such as streptomycin, neomycins, paromomycine, kanamycin, chalcomycin; the hetero-polysaccharide antibiotics made up of one saccharide part linked to an aglycone of various type through a glucoside: macrolide, pigment, pyrimidine purine. Amongst these latter are: erythromycin, magnamycin, spiramycin, oleandomycin, cinerubin and amicetin. The sugars can either play a direct role in biochemical reactions or act as a dissolving agent, as far as the anti-microbe power of these antibiotics is concerned. (author) [fr
Chaussade, H; Sunder, S; Bernard, L; Coloby, P; Guy, L; Karsenty, G; Bastide, C; Bruyère, F
To define prescription modalities for the use of antibiotics in urology. A bibliographic research was performed using the MEDLINE database concerning all the antibiotics usable in urology. Treatments were classified by families; modes of action, indications in urology and adverse events have been detailed. Administrative files for commercial use have been consulted and associated with literature analysis. About 8 classes of antibiotics are usable in urology in a routine use. How they work, indications in urology and adverse events are discussed. Knowing that bacterial resistance to quinilones is increasing dramatically, it seems imperative to control the use of 8 classes of antibiotics. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
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 youâve 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.
Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.
The anti-tumor effect of PDC on cervical cancer was investigated in vivo in mice injected with Hela cells. The parameters measured were tumor volume and weight. In vitro anti-tumor effects of PDC were assessed by measuring expressions of caspase-3, caspase-9 and P53 proteins in Hela cells via ELISA assay. Thymus ...
On day 21, six animals in each group were sacrificed for observation of antitumor activity and the remaining animals were observed to determine host the life span. Antitumor effect was determined by evaluating tumor volume, viable and nonviable tumor cell count and hematological parameters of the host. The standard ...
Purpose: To investigate the anti-tumor effects of polysaccharides from Curculigo orchioides (PDC) on cervical cancer and the possible mechanisms involved. Methods: A Box–Behnken design (BBD) was employed to optimize extraction conditions for PDC. The anti-tumor effect of PDC on cervical cancer was investigated in ...
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,
Ibragimova, V.Kh.; Aliyeva, I.N.; Aliyev, D.I.
Full text: This work deals with comparative analysis of physicochemical characteristics of dimethyl sulfoxide (DMSO) and polyene antibiotics (PA), their separate and combined effects on the membrane permeability. Radioprotective and antitumor properties of DMSO-PA complex and the prospects of its use in medicine are discussed. Our data show that DMSO has certain radioprotective properties. A single intraperitoneal injection of 0,01 ml DMSO to mice of 18-20 g body weight 30 min prior to irradiation increased the viability of animals. Thus, the survival of experimental animals by the twelfth day after irradiation was 29 %, whereas the animals of the control group died. Radioprotective properties of DMSO are enhanced upon its combination with PA. The latter was injected intraperitoneally to mice from mother liquor (1 mg antibiotic per 1 ml DMSO) in a dosage of 0.01 mg/kg animal body weight, 30 min before irradiation to 7 Gy. Among the PA studied, the most efficient were levorin and methylated levorin complexed with polyvinylpyrrolidone (PVP). The viability of experimental animals by the twelfth after irradiation was 100 %, versus only 33.3 % in control.The enhancement of radioprotective properties of DMSO complexed with PA is, probably, due to the fact that owing to the existence in PA molecules of a conjugated double bonds, a significant part of the energy of ionizing radiation can be absorbed by this system
Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962
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)
... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Antibiotic-Resistant Gonorrhea Basic Information Recommend on Facebook Tweet Share Compartir Antibiotic-Resistant Gonorrhea: An Overview Antibiotic resistance is the ...
Mohr, Kathrin I
For thousands of years people were delivered helplessly to various kinds of infections, which often reached epidemic proportions and have cost the lives of millions of people. This is precisely the age since mankind has been thinking of infectious diseases and the question of their causes. However, due to a lack of knowledge, the search for strategies to fight, heal, and prevent the spread of communicable diseases was unsuccessful for a long time. It was not until the discovery of the healing effects of (antibiotic producing) molds, the first microscopic observations of microorganisms in the seventeenth century, the refutation of the abiogenesis theory, and the dissolution of the question "What is the nature of infectious diseases?" that the first milestones within the history of antibiotics research were set. Then new discoveries accelerated rapidly: Bacteria could be isolated and cultured and were identified as possible agents of diseases as well as producers of bioactive metabolites. At the same time the first synthetic antibiotics were developed and shortly thereafter, thousands of synthetic substances as well as millions of soil borne bacteria and fungi were screened for bioactivity within numerous microbial laboratories of pharmaceutical companies. New antibiotic classes with different targets were discovered as on assembly line production. With the beginning of the twentieth century, many of the diseases which reached epidemic proportions at the time-e.g., cholera, syphilis, plague, tuberculosis, or typhoid fever, just to name a few, could be combatted with new discovered antibiotics. It should be considered that hundred years ago the market launch of new antibiotics was significantly faster and less complicated than today (where it takes 10-12 years in average between the discovery of a new antibiotic until the launch). After the first euphoria it was quickly realized that bacteria are able to develop, acquire, and spread numerous resistance mechanisms
Allison, Michael G; Heil, Emily L; Hayes, Bryan D
Prescribing antibiotics is an essential component of initial therapy in sepsis. Early antibiotics are an important component of therapy, but speed of administration should not overshadow the patient-specific characteristics that determine the optimal breadth of antimicrobial therapy. Cultures should be drawn before antibiotic therapy if it does not significantly delay administration. Combination antibiotic therapy against gram-negative infections is not routinely required, and combination therapy involving vancomycin and piperacillin/tazobactam is associated with an increase in acute kidney injury. Emergency practitioners should be aware of special considerations in the administration and dosing of antibiotics in order to deliver optimal care to septic patients. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Full Text Available Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2Ã¢Â€Â™-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2Ã¢Â€Â™-hydroxychalcones, showed the mayor structure-activity pattern along the series.
Full Text Available Onconase (ranpirnase is a homologous protein obtained from [i]Rana pipiens [/i]frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease (RN-ase activity. Onconase induces cell death through the decomposition of inner cellular RNA, inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC.
Wright, Gerard D
Antibiotics are essential for both treating and preventing infectious diseases. Paradoxically, despite their importance as pillars of modern medicine, we are in danger of losing antibiotics because of the evolution and dissemination of resistance mechanisms throughout all pathogenic microbes. This fact, coupled with an inability to bring new drugs to market at a pace that matches resistance, has resulted in a crisis of global proportion. Solving this crisis requires the actions of many stakeholders, but chemists, chemical biologists, and microbiologists must drive the scientific innovation that is required to maintain our antibiotic arsenal. This innovation requires (1) a deep understanding of the evolution and reservoirs of resistance; (2) full knowledge of the molecular mechanisms of antibiotic action and resistance; (3) the discovery of chemical and genetic probes of antibiotic action and resistance; (4) the integration of systems biology into antibiotic discovery; and (5) the discovery of new antimicrobial chemical matter. Addressing these pressing scientific gaps will ensure that we can meet the antibiotic crisis with creativity and purpose.
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
Full Text Available Mitoxantrone is an antineoplastic agent approved for clinical use in the secondary progressive phase of multiple sclerosis (MS. Several scientific reports indicate that mitoxantrone acts through the induction of short-term cell lysis at high concentrations and long-term induction of programmed cell death at lower concentrations of antigen-presenting cells. In this paper, we present the potential cytotoxic effects of mitoxantrone on the cells of the immune system, whose activity is associated with their degenerative effects on axonal myelin sheaths. The article also evaluates the results from the hospital treatment of patients diagnosed with MS. The presented data indicate that, apart from the cytostatic properties, mitoxantrone also exhibits side effects of its clinical application. This drug has high cardiotoxicity, and is associated with decreased left ventricular ejection fraction and increased risk of congestive heart failure. Therefore researchers are currently looking for new substances that can reduce the toxic effects of mitoxantrone in healthy tissues, resulting in the generation of reactive oxygen species during its metabolism.
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.
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....
Malo, Sara; José Rabanaque, María; Feja, Cristina
as their exposure to antibiotics. Data on outpatient prescribing of antimicrobials (ATC J01) in 2010 were obtained from a prescription database covering Aragón (northeastern Spain). The antimicrobial consumption at the individual level was analysed both according to the volume of DDD and the number of packages...... purchased per year. Heavy antibiotic users were identified according to Lorenz curves and characterized by age, gender, and their antimicrobial prescription profile. Lorenz curves demonstrated substantial differences in the individual use of antimicrobials. Heavy antibiotic users (5% of individuals...... with highest consumption) were responsible for 21% of the total DDD consumed and received ≥6 packages per year. Elderly adults (≥60 years) and small children (0-9 years) were those exposed to the highest volume of antibiotics and with the most frequent exposure, respectively. Heavy users received a high...
Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui
It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really ...
.... This AA induced autoimmune-like response exerts limited anti-tumor activity in a murine prostate cancer model, but could be synergistic with CTLA-4 blockade that promotes the development of autoreactive T cell...
Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the eastern Mediterranean sea. ... African Journal of Biotechnology ... algal extracts obtained from the marine algae Scytosiphon lomentaria, Padina pavonica, Cystoseira mediterranea (Phaeophyceae), Hypnea musciformis and ...
Sang Hee Lee
Full Text Available Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs and various data such as pharmacokinetic (PK and pharmacodynamic (PD properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST, clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care, the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing. The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.
, Neşe Ersöz Gülçelik, Dilara Zeybek, Fige
Propolis is a natural bee product with several pharmacological activities. Nowadays, it is also investigated for its antitumor properties. There are contraversies on the antitumor activity of propolis, not all tumour cells seem to respond to propolis treatment. The aim of our study is to evaluate the activity of propolis on differantiated thyroid cancer cell lines. Tyripan blue test and MTT assay were performed to evaluate the cell viability of B-CPAP cells after propolis treatment and compar...
Zhang, Chun Li; Li, Tai Hua; Niu, Shuang Huan; Wang, Rong Fu; Fu, Zhan Li; Guo, Feng Qin; Yang, Ming
Five new organogermanium sesquioxides have been synthesized and characterized by elemental analysis and IR spectra. All the compounds were tested for antitumor activities against KB, HCT, and Bel cells in vitro. Compound 5 ( -thiocarbamido propyl germanium sesquioxide) showed excellent antitumor activity, and its inhibition yield to KB, HCT, and Bel cells was 92.9%, 84.9%, and 70.9%, respectively. A rapid method was described for the labeling compound 5 with 9 9 m T c , and the optimum labe...
Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua
Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ga...
Padhye, Subhash; Afrasiabi, Zahra; Sinn, Ekk; Fok, Jansina; Mehta, Kapil; Rath, Nigam
The crystal structure of the potential antitumor metal compound, viz. chloro, mono(phenanthrenequinone thiosemicarbazonato) palladium(II) dimethyl formamide solvate, is reported. The central palladium(II) atom is in a square planar environment provided by the tridentate, monoanionic thiosemicarbazone ligand and the ancillary chloride ion. The compound exhibited remarkable activity against drug-sensitive and drug-resistant breast cancer cell lines and was relatively nontoxic toward the normal mammary epithelial cells. The drug-induced killing effect against breast cancer cell lines was predominantly mediated via apoptosis, a physiologic form of cell death.
Pippa, Natassa [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Pispas, Stergios [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute (Greece); Demetzos, Costas, E-mail: email@example.com [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Sivolapenko, Gregory [University of Patras, Laboratory of Pharmacokinetics, Department of Pharmacy (Greece)
In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.
Kurita, Masahiro; Takada, Tomomi; Wakabayashi, Noriko; Asami, Satoru; Ono, Shinichi; Uchiyama, Taketo; Suzuki, Takashi
Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. We found that one of the burchellin derivatives (compound 4 ) exerted cytotoxicity against the neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound 4 induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). Compound 4 exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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
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. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.
van Daalen, F.V.
Better use of current antibiotic agents is necessary to help control antimicrobial resistance (AMR). Antibiotic stewardship programs (ASPs) are introduced to coordinate activities to measure and improve appropriate antibiotic use in daily hospital practice. This thesis shows how the introduction of
Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff
The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.
Munita, Jose M.; Arias, Cesar A.
Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291
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
One of the major threats to human health in the 21st century is the emergence of pathogenic bacteria that are resistant to multiple antibiotics, thereby limiting treatment options. An important route through which pathogens become resistant is via acquisition of resistance genes from environmental
... in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. Printed in the USA Library of Congress Cataloging-in-Publication Data Antibiotics in laboratory medicine / [edited by] Victor Lorian. - 5th ed...
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. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lindenbaum, John; Greenough, William B.; Islam, M. R.
Recent clinical trials having established the value of tetracycline as an adjunct to fluid and electrolyte replacement in cholera treatment, a controlled trial of antibiotic therapy was conducted in Dacca on 318 adults hospitalized for cholera. The effects of 4 antibiotics orally administered in varying dosage schedules were studied. Cholera therapy with tetracycline or chloramphenicol caused a highly significant reduction in the duration of diarrhoea and of positive culture, in stool volume, and in intravenous fluid requirement as compared with the results in controls who received intravenous fluid therapy only. Streptomycin was also effective, but to a lesser degree; paromomycin was of little value. The severity of dehydration on admission was significantly related to subsequent duration of diarrhoea regardless of whether antibiotics were given. Increasing age was associated with more prolonged purging in patients receiving antibiotics. Increasing the dose of tetracycline to 2 to 3 times that usually administered, or prolonging treatment from 2 to 4 days, did not enhance the therapeutic results. The effect of tetracycline was apparent within a few hours of administration. Bacteriological relapses were seen after discontinuation of therapy in all treatment groups, but were not due to the development of resistant bacteria. PMID:4865453
One of the major threats to human health in the 21st century is the emergence of pathogenic bacteria that are resistant to multiple antibiotics, thereby limiting treatment options. An important route through which pathogens become resistant is via acquisition of resistance genes from
Walsh, Ciara; Duffy, Geraldine
Wide-spread antibiotic resistance among bacterial pathogens is now a serious public health issue and multi-antibiotic resistance has been reported in many foodborne pathogens including Salmonella and E. coli. A study to determine antibiotic resistance profiles of a range of Salmonella and Verocytotoxigenic E.coli (VTEC) isolated from Irish foods revealed significant levels of antibiotic resistance in the strains. S. typhimurium DT104 were multiantibiotic resistant with 97% resistant to 7 anti...
... 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 ...
Therapeutic anti-cancer vaccines containing tumor-specific antigens recognized by T lymphocytes are thought to stimulate high numbers of anti-vaccine cytolytic T lymphocytes (CTL) which then can lyse the tumor cells. To understand why these vaccines are followed by tumor regressions in only 10% of the patients, we analysed the tumor-specific immune responses of these patients. Contrary to our expectations, the anti-vaccine CTL responses were of very low level. However, regressing tumors were massively infiltrated by anti-tumor T cells of other specificities, including new anti-tumor CTL clonotypes that emerged following vaccination. We now believe that the role of the anti-vaccine CTL is to activate or restimulate large numbers of other anti-tumor CTL. Their ability to initiate this response is probably more important than their number. These results have important consequences for the improvement of the clinical efficacy of anti-cancer vaccines.
Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice
Brett-Major, David M; Coldren, Rodney
Leptospirosis has a wide-ranging clinical and public health impact. Leptospira are globally distributed. Case attack rates are as high as 1:4 to 2:5 persons in exposed populations. In some settings mortality has exceeded 10% of infected people. The benefit of antibiotic therapy in the disease has been unclear. We sought to characterise the risks and benefits associated with use of antibiotic therapy in the management of leptospirosis. We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded regardless of study language. This was augmented by a manual search. The last date of search was November, 2011. To be included in assessment of benefits, trials had to specifically assess the use of antibiotics in a randomised clinical trial. A broad range of study types were incorporated to seek potential harms. Included trials were systematically abstracted, as were excluded studies for the purposes of assessing harms. Analyses were conducted in accordance with The Cochrane Handbook and practices of The Cochrane Hepato-Biliary Group. Seven randomised trials were included. Four trials with 403 patients compared an antibiotic with placebo or no intervention. Three trials compared at least one antibiotic regimen with another antibiotic regimen. The trials all had high risk of bias. The trials varied in the severity of leptospirosis among trial patients. The ability to group data for meta-analysis was limited. While all four trials that compared antibiotics with placebo reported mortality and used parenteral penicillin, there were no deaths in two of them. Since odds ratio calculations cannot employ zero-event trials, only two trials contributed to this estimate. The number of deaths were 16/200 (8.0%) in the antibiotic arm versus 11/203 (5.4%) in the placebo arm giving a fixed-effect OR 1.56 (95% CI 0.70 to 3.46). The
Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui
It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.
Full Text Available It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could relly replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre- and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm and virulence, and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.
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.
Martinez, Jose Luis
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.
Martinez, Jose Luis, E-mail: firstname.lastname@example.org [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.
Tundis, Rosa; Xiao, Jianbo; Loizzo, Monica R
Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents. Annonaceous acetogenins are one of the most promising classes of natural products, owing to their potential antitumor activity. However, their neurotoxicity should not be underestimated. © 2017 New York Academy of Sciences.
... that (a) homeostatic T-cell proliferation consistently elicits anti-tumor responses; (b) irradiation is more effective than Tcell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation...
Ferrer, Manuel; Méndez-García, Celia; Rojo, David; Barbas, Coral; Moya, Andrés
Our microbiome should be understood as one of the most complex components of the human body. The use of β-lactam antibiotics is one of the microbiome covariates that influence its composition. The extent to which our microbiota changes after an antibiotic intervention depends not only on the chemical nature of the antibiotic or cocktail of antibiotics used to treat specific infections, but also on the type of administration, duration and dose, as well as the level of resistance that each microbiota develops. We have begun to appreciate that not all bacteria within our microbiota are vulnerable or reactive to different antibiotic interventions, and that their influence on both microbial composition and metabolism may differ. Antibiotics are being used worldwide on a huge scale and the prescription of antibiotics is continuing to rise; however, their effects on our microbiota have been reported for only a limited number of them. This article presents a critical review of the antibiotics or antibiotic cocktails whose use in humans has been linked to changes in the composition of our microbial communities, with a particular focus on the gut, oral, respiratory, skin and vaginal microbiota, and on their molecular agents (genes, proteins and metabolites). We review the state of the art as of June 2016, and cover a total of circa 68 different antibiotics. The data herein are the first to compile information about the bacteria, fungi, archaea and viruses most influenced by the main antibiotic treatments prescribed nowadays. Copyright © 2016 Elsevier Inc. All rights reserved.
McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison
The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175
Sydenham, Rikke Vognbjerg; Pedersen, Line Bjørnskov; Plejdrup Hansen, Malene
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......) and the Danish Microbiology Database (performed microbiological testing). We will assess and quantify the use of microbiological testing prior to antibiotic prescription. Furthermore we will investigate associations between GP characteristics, use of microbiological investigations and description patterns...
Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the ...
Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E
We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.
Hui Li; Zhenyu Wang
Microbial transformation can strengthen the antioxidant and antitumor activities of polyphenols. Polyphenols contents, antioxidant and antitumor activities of pine polyphenols and its biotransformation extracts by Aspergillus niger, Aspergillus oryzae, Aspergillus carbonarius, Aspergillus candidus, Trichodermas viride, Mucor wutungkiao and Rhizopus sp were studied. Significant differences were noted in antioxidant and antitumor activities. The highest antioxidant activities in Trolox equivale...
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.
Rodríguez Alfaro, Miguel; Responsable de la cátedra de Farmacología de la Facultad de Odontología UNMSM.; Burga Sánchez, Jonny; Catedrático de Farmacología de la Facultad de Odontología UNMSM.; Chumpitaz Cerrate, Víctor; Catedrático de Farmacología de la Facultad de Odontología UNMSM.; Varas Hilario, Roberto; Catedrático de Farmacología de la Facultad de Odontología UNMSM.; Guerra Sanguinetti, Jaime; Cirujano Dentista de la Facultad de Odontología UNMSM.; López Bellido, Roger; Bachiller de la Facultad de Odontología UNMSM.; Zegarra Cuya, Juan; Interno de la Facultad de OdontoIogia UNMSM.
Surgical antibiotic prophylaxis consists in the use of an antimicrobial drug in a preventive way, that must be active against microorganisms that in high frequency causes posterior infections of our surgical wounds and maintain effective tissue concentrations along the surgery procedure and the posterior time when appears the bacteremia. To reach a successful treatment is necessary to have the knowledge of the resident bactemial flora and the pathogenous flora that infects our surgical wounds...
Johnson, Alan P.
Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439
Purpose: To optimize the extraction conditions of polysaccharides from Polygonum perfoliatum L. (PSDP) and to evaluate their anti-tumor activities on A549 cell line. Methods: Extraction of PSDP was optimized using Box-Behnken design (BBD). Three factors of response surface methodology (RSM) including extraction time ...
Purpose: To investigate the antibacterial and antitumor activities of the aerial parts of 8 different Turkish endemic plants (Phlomis russeliana, Phlomis armeniaca, Astragalus brachypterus, Astrantia maxima, Ptilostemon afer, Senecio castagneanus, Echium orientale and Arum euxinum). Methods: Two different bioassays ...
Purpose: To evaluate the antitumor activities of Platycarya strobilacea infructescence extracts in A549, HepG2, SH-SY-5Y, HCT116, and U2OS-NKFB cell lines. Methods: The total amount of phenolics in P. strobilacea infructescence based on three solvent extracts (methanol, ethyl acetate and water) was measured using ...
Biochemical and histological evidences for the antitumor potential of Teucrium Oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma. Abdelaaty A Shahat, Mansour S Alsaid, Soheir E Kotob, Husseiny A Husseiny, Amal AM Al-Ghamdi, Hanaa H Ahmed ...
Purpose: To optimize the extraction conditions of polysaccharides from the root of Senecio scandens. Buch,-Ham. (PRS) and evaluate its anti-tumor effect on hepatocellular carcinoma. Methods: Response surface methodology (RSM) applied with a Box-Behnken design (BBD, three levels and three factors) was employed to ...
Myxobacteria are gliding gram-negative bacteria and a class of prokaryote with complicated multicellular behaviors and morphogenesis. Reports show that myxobacteria generally produce large families of secondary metabolites with various bioactivities, such as antifungal and anti-tumor activities. In this paper, two strains ...
Elisa del Río del Rosal
Full Text Available ABSTRACT Introduction: Propolis is the substance that protects the hive, a resin of complex and viscous composition bees use in the repair and protection of the hive. The material from which propolis arises are the resins, shoots and petioles of the leaves of different plants, so it has a very complex chemical composition that varies depending on the flora of the bees collection. It offers an antimicrobial, anti-inflammatory capacity related to its antioxidant, immunomodulatory power, among others. Aims: In this work, antioxidant and antitumoral activities of different propolis collected from different areas of the province of Malaga, comparing them with one from the Bohemian region to the south of the Czech Republic are studied. Material and methods: Antioxidant activity was determined according to the ABTS+/S2O8K2 method. In addition, the quantity of total proteins from the nitrogen content and subsequently the cytotoxicity and antitumoral activity of the propolis of Puerto de la Torre, north of Malaga, are measured according to the 3-(4,5-dimetiltiazol-2-il-2,5-diphenyl tetrazolium bromide method. Results: It was observed that propolis has high antioxidant activity, although it has a lower amount of proteins. Propolis has high toxicity and higher antitumoral activity against colon cancer than leukemia. Discussion: With all these data, it can be concluded that propolis offers different activities of interest, for the food and cosmetic industry, among which the high antioxidant and antitumoral capacity.
In vivo, PSG also had significant anti-tumor activity in nude mouse xenograft model (p < 0.05), inhibiting tumor growth. Furthermore, the results showed that treatment with PSG (20, 40 and 60 μg/mL) for 24 h resulted in significantly increased apoptosis in HeLa cells (p < 0.05). Additionally, Western blot analysis revealed that ...
Original Research Article. Anti-tumor effect of polysaccharides isolated from. Taraxacum mongolicum Hand-Mazz on MCF-7 human breast cancer cells. Hu Niu1,2, JunWei Fan3, ... leading cause of cancer-related death in women worldwide . Currently, breast cancer is the most common cancer among women in China,.
Xu Bo; Sun Qixun; Zhang Nianbao; Xie Binghua; Zhang Jiong
Liposome vesicles containing antitumor drug methotrexate (MTX) were prepared. MTX was labelled by the tritium ion beam method. After purification by TLC, the specific radioactivity of 3 H-MTX was 1.19 GBq/mmol with radiochemical purity orver 95%. Under various forming conditions of liposome vesicles, the efficiency of encapsulation was 21-53%
Li, Xiao-gang; Pan, Wei-dong; Zhang, Xiao-jie; Xiao, Jian-hui
To seperate and identify the chemicals from the antitumor fraction of Cordyceps taii mycelia powder. The mycelia of Cordyceps taii were prepared by the submerged fermentation technique. Chemical entities in the antitumor fraction of Cordyceps taii were isolated and purified by using different column chromatographies (silica gel, Sephadex LH-20 and MCI), and semi-preparative HPLC method. Theirs chemical structures were then identified by different spectrum techniques such as EI, ESI and 1D/2D-NMR, etc. The cytotoxic activity was investigated by the Sulforhodamine B (SRB) assay. Six compounds, such as 5α,8α-epidioxyergosta-6,22-dien-3β-ol (1), ergosterol (2), adenine nucleoside (3), helvolic acid (4), deacetylcytochalasin C (5) and zygosporin D (6), were identified. The IC50 value of compound 2 against human gastric cancer cell line SGC-7901 was 5.99 μmol/L, which was less than the half value of cisplatin, and had lower cytotoxicity to normal cells in comparison with cisplatin. Six compounds have been isolated from the antitumor fraction of Cordyceps taii mycelia powder,of which compounds 1, 5 and 6 are isolated from Cordyceps taii for the first time. Compounds 1, 2 and 4 have cytotoxic activities against cancer cells, and should be the main antitumor compounds of Cordyceps taii.
The effects of extraction temperature, liquid-solid ratio and extraction time on the yield of PTM were investigated using a Box-Behnken design (BBD). The in vitro anti-tumor effect of PTM on MCF-7 cells was investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, while the mechanism of PTM-induced ...
Purpose: To optimize the extraction conditions of polysaccharides from the root of Senecio scandens Buch,-Ham. (PRS) and evaluate its anti-tumor effect on hepatocellular carcinoma. Methods: Response surface methodology (RSM) applied with a Box-Behnken design (BBD, three levels and three factors) was employed to ...
1Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, National Engineering Lab. for Biomass. Chemical Utilization ... Conclusion: The study confirms the antitumor activities of ethyl acetate and methanol extracts of P. strobilacea ..... The authors are grateful to the Natural Science. Foundation of ...
Purpose: To evaluate the antitumor activity of doxorubicine (DOX) loaded nanoemulsion (NE) on Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Methods: The mice were divided into five groups (n = 20) according to the administered drug. Groups I - V were labeled as negative control (normal), positive control ...
May 15, 2012 ... (2004). The chitosan, extracted from M. domestica was found to have effect on fungus and bacteria (Ai et al., 2008, 2012) while the extract from the larvae of the housefly exhibited antibacterial activity and in vitro anti-tumor activity (Hou et al., 2007a). In addition, Hf-1, a novel antibacterial peptide, was also.
Leibovici, Leonard; Paul, Mical; Garner, Paul
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...
Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua
Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC50) values of Ganoderma extracts on HL60, K562 and SGC-7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle. PMID:27900038
Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua
Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC 50 ) values of Ganoderma extracts on HL60, K562 and SGC-7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC 50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle.
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. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810
Jiang, Xinglin; Ellabaan, Mostafa M Hashim; Charusanti, Pep
It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify genes in proteobacteria, including some pathogens......, that appear to be closely related to actinobacterial ARGs known to confer resistance against clinically important antibiotics. Furthermore, we identify two potential examples of recent horizontal transfer of actinobacterial ARGs to proteobacterial pathogens. Based on this bioinformatic evidence, we propose...... results support the existence of ancient and, possibly, recent transfers of ARGs from antibiotic-producing actinobacteria to proteobacteria, and provide evidence for a defined mechanism....
Fernandes, Prabhavathi; Martens, Evan
Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Shang, Yuanhong; Du, Qingdan; Liu, Simei; Staadler, Maksorvor; Wang, Shu; Wang, Dongdong
Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of isosteroidal alkaloids include antihypertensive, antitussive, anti-inflammatory, antithrombosis, among others. Recently, some studies show that this kind of alkaloids exhibited significant antitumor activity. To the best of our knowledge, there is no review focusing on their antitumor activity and mechanism of their antitumor activity. To fill the gap, in this review, we summarized antitumor effects of the isosteroidal alkaloids from genus Veratrum and Fritillaria on different tumors and the mechanisms of their antitumor activity. In conclusion, this kind of alkaloids has extensive antitumor activity, and there are several main mechanisms of their antitumor activity, including the Hedgehog signaling pathway, caspase-3 dependent apoptosis, cell cycle, and autophagy. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Dinos, George P
Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases. © 2017 The British Pharmacological Society.
Khopade, Ajay J; Arulsudar, N; Khopade, Surekha A; Hartmann, J
Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn(2+) ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn(2+) in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn(2+) and PSS/TbS/Zn(2+) complexes forming the capsule wall. The TbS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of
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.
Full Text Available The problem of antibiotic resistance is a serious threat to the global public health and requires action by both the state and the public. The World Health Organization identified 15 most dangerous and prevalent superbugs, which it ranked based on three levels of threat they present to the public health. At the heart of the fight against antibiotic resistance lies the increased awareness of the health professionals and general public that incorrect and excessive use of antibiotics amid poor practices in infection prevention and control contributes to the acceleration of antibiotic resistance.
... of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ. 2017;189:625. American College of Obstetricians ... Foundation for Medical Education and Research (MFMER). All rights reserved.
Gorski, Armin; Hamouda, Khaled; Özkur, Mehmet; Leistner, Markus; Sommer, Sebastian-Patrick; Leyh, Rainer; Schimmer, Christoph
Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients. A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. The response to the questionnaire was 87.3%. All clinics that responded use antibiotic prophylaxis, 79% perform it not longer than 24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses: 8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first-generation cephalosporin). If sepsis is suspected, the following diagnostics are performed routinely: wound inspection 100%; white blood cell count 100%; radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%, blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography 75%. The calculated empiric antibiotic therapy (depending on the suspected focus) consists of a multidrug combination with broad-spectrum agents. This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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
Barton, Mary D; Pratt, Rachael; Hart, Wendy S
There is currently no systematic surveillance or monitoring of antibiotic resistance in Australian animals. Registration of antibiotics for use in animals is tightly controlled and has been very conservative. Fluoroquinolones have not been registered for use in food producing animals and other products have been removed from the market because of human health concerns. In the late 1970s, the Animal Health Committee coordinated a survey of resistance in Salmonella and Escherichia coli isolates from cattle, pigs and poultry and in bovine Staphylococcus aureus. Some additional information is available from published case reports. In samples collected prior to the withdrawal of avoparcin from the market, no vancomycin resistant Enterococcus faecium or Enterococcus faecalis were detected in samples collected from pigs, whereas some vanA enterococci, including E. faecium and E. faecalis, were found in chickens. No vanB enterococci were detected in either species. Virginiamycin resistance was common in both pig and poultry isolates. Multiple resistance was common in E. coli and salmonellae isolates. No fluoroquinolone resistance was found in salmonellae, E. coli or Campylobacter. Beta-lactamase production is common in isolates from bovine mastitis, but no methicillin resistance has been detected. However, methicillin resistance has been reported in canine isolates of Staphylococcus intermedius and extended spectrum beta-lactamase producing E. coli has been found in dogs.
Cohen, R; Raymond, J; Hees, L; Pinquier, D; Grimprel, E; Levy, C
The implementation of pneumococal conjugate vaccines (PCVs) 7 then 13 valent (Prevenar13 ®) in 2010-2011 has significantly changed the profile of pneumococcal meningitis. Since 3 years, the National Pediatric Meningitis Network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have reported no cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (3GC): cefotaxime or ceftriaxone. In the light of these new data, vancomycin should no longer be prescribed at the initial phase of pneumococcal meningitis treatment (confirmed or only suspected) and this antibiotic should only be added when 3GC minimum inhibitory concentration of the strain isolated is greater than 0.5mg/L. For meningococcal meningitis, nearly 20% of strains have decreased susceptibility to penicillin and amoxicillin, but all remain susceptible to 3GC. The National Pediatric Meningitis Network is a valuable tool because it has been sufficiently exhaustive and sustainable over 15 years. Maintaining this epidemiologic surveillance will allow us to adapt, if necessary, new regimens for subsequent changes that could be induced by vaccination and/or antibiotic uses. © 2017 Elsevier Masson SAS. Tous droits réservés.
Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Full Text Available Phospholipases type A2 (PLA2s are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2 (sPLA2 are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2 isolated from Tunisian vipers: Cerastes cerastes and Macrovipera lebetina, representing new tools to target specific integrins, mainly, and integrins.
Full Text Available A novel series of biscoumarin (1–4 and dihydropyran (5–13 derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 1–4 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB energy in their structures.
Wang, Xiaoqin; Zhang, Xuewu
Chlorella pyrenoidosa is a unicellular green algae and has been a popular foodstuff worldwide. However, no reports on the antitumor peptides from such a microalgae are available in the literature. In this study, using low-temperature high-pressure extraction, enzymatic hydrolysis, ion exchange, and gel filtration chromatography, we separated a polypeptide that exhibited inhibitory activity on human liver cancer HepG2 cells, and named the polypeptide CPAP (C. pyrenoidosa antitumor polypeptide). Furthermore, the micro- and nanoencapsulation of CPAP were investigated by using two methods: complex coacervation and ionotropic gelation. The in vitro release tests revealed that CPAP was well preserved against gastric enzymatic degradation after micro/nanoencapsulation and the slowly controlled release in the intestine could be potentially achieved. These results suggest that CPAP may be a useful ingredient in food, nutraceutical, and pharmaceutical applications. © 2013 American Institute of Chemical Engineers.
Marianna Vieira Sobral
Full Text Available Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.
Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.
Hu, Liping; Ying, Jie; Zhang, Miaomiao; Qiu, Xiaoyan; Lu, Yu
Compounds obtained from natural resources have been the important candidates for the discovery and development of drugs. Over the past few decades, marine resources gradually attracted the attention of the majority of researchers, and a number of compounds with various structures or activities have been obtained from sponge, alga, fungus, mollusks and some others. Because of the living conditions in the ocean are higher pressures, more variable temperatures, lower oxygen and lower light than that in the terrestrial environment, marine resources have a lot of organisms that are not available or rare on land. It is expected to find agents exhibited good activity for diseases treatment from marine organisms, especially anti-tumor activity. Among the marine compounds obtained, most of them have the good antitumor activities, and some have been used for clinical treatment of tumors, some are in clinical trials. These natural products through different pathways do their unique antitumor effects to induce cells apoptosis, inhibit cells proliferation and migration. A variety of drugs have been used for the clinical treatment of cancer during the last few years, but for the advanced cancer patients, extending the survival time is not long. And due to the lack of effective drugs to control the transfer of cancer cells and with the development of drug-resistant microbes, researchers are actively looking for active compounds to overcome these problems. Here, we summarized the marine natural products obtained during the past few years, and analyzed their anti-tumor effects and mechanism. This will provide a significant basis for anticancer drugs' screening and development. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Full Text Available Antibiotic Resistance is an international threat, killing thousands and infecting millions. Although certain populations may be at an increased risk for infections, anyone can find themselves compromised with a multi-drug resistant infection. Treatments are becoming more complicated as the bacteria becomes more elusive. Cures are becoming less certain, and the future antibiotic arsenal is looking thin. Although there are many talented scientists and capable drug development entities, the funding and returns on investment are not sufficient to entice antibiotic research and development. This paper explores the current situation regarding antibiotic resistance and its casualties, as well as the mechanisms being employed to overcome the increase in resistance, and decrease in antibiotic effectiveness. Through analysis of antibiotic research, development, and regulation, this paper adds to the discussion by filling in the current gaps regarding the procurement of sustainable funding via an insurance model framework. By incentivizing the pharmaceutical industry to invest in antibiotic research, and by guaranteeing returns on investment, a global solution to the current antibiotic resistance problem can be contained. Type: Student Project
May 1, 2010 ... of E. coli, Salmonella spp., Campylobacter spp and antibiotic resistance genes from these bacteria may be co-transferred to humans (4,5). The shedding of pathogens by asymptomatic animals is increasing concern as a source, distribution of food borne diseases. (FBDs) and antibiotic resistance (6-8).
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…
Monica Cristina Cara,
Full Text Available Next to the beta-lactam antibiotics in veterinary medicine, streptomycin is one of the mostly used antibiotics. High concentration of streptomycin could lead to ototoxic and nephrotoxic effects. Low concentration – as found in food – may cause allergies, destroy the intestinal flora and favor immunity to some pathogenic microorganisms. In 1948 chlortetracycline was isolated by Duggan as a metabolite and this was the first antibiotic substance of the group of tetracyclines. In the present paper there are presented the monitoring of the antibiotic residues in honey from Timis County. The residues of tetracycline and streptomycin in honey were determined by the method ELISA – a quantitative method of detection. The microtitre wells are coated with tetracycline and anti-streptomycin antibodies. Free antibiotic and immobilized antibiotic compete with the added antibiotic antibody (competitive immunoassay reaction. Any unbound antibody is then removed in a washing step. Bound conjugate enzymes convert the colorless chromogen into a blue product. The addition ofthe stop reagent leads to a color change from blue to yellow. The measurement is made photometrically at 450 nm. The absorption is inversely proportional to the antibiotic concentration in the sample.
Queiroz, Rodrigo Guimaraes
Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)
Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C.; Sawai, Masaharu; Pinkerton, Kent E.; Takeuchi, Minoru
Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489
Noori, Shokoofe; Hassan, Zuhair M; Yaghmaei, Bahram; Dolatkhah, Milad
Development of agents that specifically kill cancer cells and simultaneously elicit antitumor immune response is a step forward in cancer therapy. Immunostimulation can result in eliminating of the cancer cells; immunotherapy is a promising approach in balancing the immune response by Treg. In the present study, we investigated whether the administration of salvigenin contributes to the augmentation of antitumor immunity and the regression of tumor tissues in a mouse model of breast cancer. Salvigenin was purified from Tanacetum canescens, and its effect on the tumor volume was investigated. The splenocyte proliferation, shifting of cytokine profile, and the presence of naturally-occurring CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune response. Our results demonstrated that a significant decrease in the level of IL-4 and increase in the IFN-γ in the animals treated with salvigenin and significant decreased in the level of splenic CD4+CD25+Foxp3+ T regulatory cells. The cytotoxic and immunomodulatory properties of salvigenin were acknowledged in vivo. Copyright © 2013. Published by Elsevier Inc.
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.
Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.
Full Text Available The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae, which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA, against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50 for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.
Zhang, Bochao; Zhang, Xuewu
Spirulina platensis is a multicellular edible blue-green alga with abundant proteins (∼ 60%). No report is available on the antitumor polypeptides from the whole proteins of S. platensis. In this study, for the first time, an antitumor polypeptide Y2 from trypsin digest of S. platensis proteins was obtained by using freeze-thawing plus ultrasonication extraction, hydrolysis with four enzymes (trypsin, alcalase, papain, and pepsin), and gel filtration chromatography. The results showed that the degree of hydrolysis can be ordered as: trypsin (38.5%) > alcalase (31.2%) > papain (27.8%) > pepsin (7.1%). For MCF-7 and HepG2 cells, at 250 µg/mL, the maximum inhibitory rate of Y2 was 97%, while standard drug 5-FU was 55 and 97%, respectively. Furthermore, the nanoencapsulation of Y2 with chitosan (CS) was also investigated. After nanoencapsulation, the maximum encapsulation efficiency and polypeptides contents are 49 and 15%, respectively; and the antitumor activity is basically not lost. These data demonstrated the potential of nanopolypeptides (Y2-CS) in food and pharmaceutical applications. © 2013 American Institute of Chemical Engineers.
Speedie, M K; Fique, D V; Blomster, R N
After modification, a technique for radiometrically measuring bacterial growth has been applied to a mutant strain of Saccharomyces cerevisiae. The assay is based on inhibition of 14CO2 release from [14C]glucose, which provides an extremely sensitive measure of cellular respiratory activity and growth. The criterion for antitumor activity is the differential inhibition of wild-type and mutant (distorted cell membrane) strains of the yeast. The system was optimized for medium, time of incubation, temperature, and size of inoculum. Known antitumor agents, including bleomycin, actinomycin D, adriamycin, and ellipticine were tested in the system, and differential inhibition was observed. Vincristine showed no inhibitory effects at the concentrations tried. The sensitivity for 20% inhibition ranged from 0.8 micrograms of adriamycin per ml to 0.14 mg of ellipticine per ml. Antifungal agents such as amphotericin B exhibited no differential inhibition. Antibacterial agents were inactive. This method may provide a rapid, sensitive, in vitro quantitative assay for antitumor agents which could be applied to a variety of assay needs and which can be run with facilities and equipment available in most laboratories.
Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography. M Brand, D Bisoz. Abstract. Background. Antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is controversial. We set out to assess the current antibiotic prescribing practice among ...
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...... are the most effective. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 3); MEDLINE (1950 to May 2007) and EMBASE (1974 to June 2007). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing antibiotics with placebo...... or 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...
Perry, Julie; Waglechner, Nicholas; Wright, Gerard
Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.
Ciofu, Oana; Rojo-Molinero, Estrella; Macià, María D.
Bacterial biofilms are associated with a wide range of infections, from those related to exogenous devices, such as catheters or prosthetic joints, to chronic tissue infections such as those occurring in the lungs of cystic fibrosis patients. Biofilms are recalcitrant to antibiotic treatment due...... to multiple tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm infections in spite of antibiotic exposure which predisposes to antibiotic resistance development (genetic resistance). Understanding the interplay between phenotypic and genetic resistance mechanisms acting...... on biofilms, as well as appreciating the diversity of environmental conditions of biofilm infections which influence the effect of antibiotics are required in order to optimize the antibiotic treatment of biofilm infections. Here, we review the current knowledge on phenotypic and genetic resistance...
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......-day reduction in duration of cough. However, at follow-up there are no significant differences in overall clinical improvement inpatients treated with antibiotics compared with those receiving placebo. Despite this, antibiotics are administered to approximately two thirds of these patients. This review...... 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...
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....
González-Torralba, Ana; García-Esteban, Coral; Alós, Juan-Ignacio
Infectious gastroenteritis remains a public health problem. The most severe cases are of bacterial origin. In Spain, Campylobacter and Salmonella are the most prevalent bacterial genus, while Yersinia and Shigella are much less frequent. Most cases are usually self-limiting and antibiotic therapy is not generally indicated, unless patients have risk factors for severe infection and shigellosis. Ciprofloxacin, third generation cephalosporins, azithromycin, ampicillin, cotrimoxazole and doxycycline are the most recommended drugs. The susceptibility pattern of the different bacteria determines the choice of the most appropriate treatment. The aim of this review is to analyse the current situation, developments, and evolution of resistance and multidrug resistance in these 4 enteric pathogens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Guidugli, Fábio; Castro, Aldemar A; Atallah, Alvaro N; Araújo, Maurício G
Leptospirosis is a parasitic disease transmitted by animals. Severe leptospirosis may result in hospitalisation and about five per cent of the patients die. In clinical practice, penicillin is widely used for treating leptospirosis. To evaluate the effectiveness and safety of antibiotics versus placebo or other antibiotic regimens in treating leptospirosis. We addressed the following clinical questions: a) Are treatment regimens with antibiotics more efficient than placebo for leptospirosis? b) Are treatment regimens with antibiotics safe when compared to placebo for leptospirosis? c) Which antibiotic regimen is the most efficient and safest in treating leptospirosis? Electronic searches and searches of the identified articles were combined. Randomised clinical trials in which antibiotics were used as treatment for leptospirosis. Language, date, or other restrictions were not applied. Patients with clinical manifestations of leptospirosis. Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen). Data and methodological quality of each trial were independently extracted and assessed by two reviewers. The random effects model was used irrespective of significant statistical heterogeneity. Three trials met inclusion criteria. Allocation concealment and double blind methods were not clearly described in two. Of the patients enrolled, 75 were treated with placebo and 75 with antibiotics: 61 (81.3%) penicillin and 14 (18.6%) doxycycline. The patients assigned to antibiotics compared to placebo showed: a) Mortality: 1% (1/75) versus 4% (3/75); risk difference -2%, 95% confidence interval -8% to 4%. b) Duration of hospital stay (days): weighted mean difference 0.30, 95% confidence interval -1.26 to 1.86. c) Prolonged hospital stay (> seven days): 30% (7/23) versus 74% (14/19); risk difference -43%, 95% confidence interval -70% to -16%. Number needed-to-treat 3, 95% confidence interval 2 to 7. d) Period of disappearance of fever (days
Hiramatsu, Keiichi; Igarashi, Masayuki; Morimoto, Yuh; Baba, Tadashi; Umekita, Maya; Akamatsu, Yuzuru
By screening cultures of soil bacteria, we re-discovered an old antibiotic (nybomycin) as an antibiotic with a novel feature. Nybomycin is active against quinolone-resistant Staphylococcus aureus strains with mutated gyrA genes but not against those with intact gyrA genes against which quinolone antibiotics are effective. Nybomycin-resistant mutant strains were generated from a quinolone-resistant, nybomycin-susceptible, vancomycin-intermediate S. aureus (VISA) strain Mu 50. The mutants, occurring at an extremely low rate (generation), were found to have their gyrA genes back-mutated and to have lost quinolone resistance. Here we describe nybomycin as the first member of a novel class of antibiotics designated 'reverse antibiotics'. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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.
Scribano, Maria Lia; Prantera, Cosimo
Inflammatory bowel diseases are characterized by an altered composition of gut microbiota (dysbiosis) that may contribute to their development. Antibiotics can alter the bacterial flora, and a link between antibiotic use and onset of Crohn's disease (CD), but not ulcerative colitis, has been reported. The hypothesis that Mycobacterium avium subspecies paratuberculosis (MAP) could be an etiologic agent of CD has not been confirmed by a large study on patients treated by an association of antibiotics active against MAP. The observations supporting a role of intestinal microbiota in CD pathogenesis provide the rationale for a therapeutic manipulation of the intestinal flora through the employment of antibiotics. However, current data do not strongly support a therapeutic benefit from antibiotics, and there is still controversy regarding their use as primary therapy for treatment of acute flares of CD, and for postoperative recurrence prevention. Nevertheless, clinical practice and some studies suggest that a subgroup of patients with colonic involvement, early disease, and abnormal laboratory test of inflammation may respond better to antibiotic treatment. Since their long-term use is frequently complicated by a high rate of side effects, the use of antibiotics that work locally appears to be promising.
Sommer, Morten; Dantas, Gautam
Since the discovery and clinical application of antibiotics, pathogens and the human microbiota have faced a near continuous exposure to these selective agents. A well-established consequence of this exposure is the evolution of multidrug-resistant pathogens, which can become virtually untreatable....... 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...... expand our understanding of the interplay between antibiotics and the microbiome....
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.
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 bacteria.in aquatic and marine ecosystems. Antibiotic risk assessment approaches were developed based on the use of MICs and MIC Ratios [High (Antibiotic Resistant/Low (Antibiotic Sensitive MIC] for each antibiotic indicating the range of bacterial adaptability to each antibiotic to help define the No
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.
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. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: email@example.com.
Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan
Abstract Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as “antibiotic cycling” and “antibiotic mixing.” However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to “cycle” between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. Key words: antibiotic cycling, antibiotic mixing, optimal control, stochastic models. PMID:28096304
Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan
Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. : antibiotic cycling, antibiotic mixing, optimal control, stochastic models. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Hoiby, N.; Bjarnsholt, T.; Givskov, M.
A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis...... to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute...... to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum...
Olczak, A.; Grzesiowski, P.; Hryniewicz, W.; Haaijer-Ruskamp, F.M.
Antibiotic resistance, the important public health threat, depends on antibiotic overuse/misuse. Self-medication with antibiotics is of serious medical concern. The aim of the study, as a part of SAR project (Self-medication with antibiotic in Europe) was to survey the incidence of this phenomenon.
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
Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I
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. 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. 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. 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. 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.
This study was designed to evaluate the antibiotic susceptibilities, genotypic characteristics and biofilm formation abilities of antibiotic-sensitive Staphylococcus aureus KACC 13236 (SAS), multiple antibiotic-resistant S. aureus CCARM 3080 (SAR), antibiotic-sensitive Salmonella Typhimurium KCCM 40253 (STS) and ...
Hu, Xiao; Liu, Xikui; Moisan, Jacques; Wang, Yahong; Lesch, Charles A.; Spooner, Chauncey; Morgan, Rodney W.; Zawidzka, Elizabeth M.; Mertz, David; Bousley, Dick; Majchrzak, Kinga; Kryczek, Ilona; Taylor, Clarke; Van Huis, Chad; Skalitzky, Don; Hurd, Alexander; Aicher, Thomas D.; Toogood, Peter L.; Glick, Gary D.; Paulos, Chrystal M.; Zou, Weiping; Carter, Laura L.
ABSTRACT RORγt is the key transcription factor controlling the development and function of CD4+ Th17 and CD8+ Tc17 cells. Across a range of human tumors, about 15% of the CD4+ T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol. These RORγ agonists enhance effector function of Type 17 cells by increasing the production of cytokines/chemokines such as IL-17A and GM-CSF, augmenting expression of co-stimulatory receptors like CD137, CD226, and improving survival and cytotoxic activity. RORγ agonists also attenuate immunosuppressive mechanisms by curtailing Treg formation, diminishing CD39 and CD73 expression, and decreasing levels of co-inhibitory receptors including PD-1 and TIGIT on tumor-reactive lymphocytes. The effects of RORγ agonists were not observed in RORγ−/− T cells, underscoring the selective on-target activity of the compounds. In vitro treatment of tumor-specific T cells with RORγ agonists, followed by adoptive transfer to tumor-bearing mice is highly effective at controlling tumor growth while improving T cell survival and maintaining enhanced IL-17A and reduced PD-1 in vivo. The in vitro effects of RORγ agonists translate into single agent, immune system-dependent, antitumor efficacy when compounds are administered orally in syngeneic tumor models. RORγ agonists integrate multiple antitumor mechanisms into a single therapeutic that both increases immune activation and decreases immune suppression resulting in robust inhibition of tumor growth. Thus, RORγ agonists represent a novel immunotherapy approach for cancer. PMID:28123897
Full Text Available Using a highly effective binuclear Cu complex as the catalyst, the 1,3-dipolar cycloaddition reactions between 16 alkynes and two azides were successfully performed and resulted in the production of 25 new triazole-containing sorafenib analogs. Several compounds were evaluated as potent antitumor agents. Among them, 4-(4-(4-(3-fluorophenyl-1H-1,2,3-triazol-1-ylphenoxy-N-methylpicolinamide (8f potently suppressed the proliferation of HT-29 cancer cells by inducing apoptosis and almost completely inhibited colony formation at a low micromolar concentration.
Hu, Xiao; Liu, Xikui; Moisan, Jacques; Wang, Yahong; Lesch, Charles A.; Spooner, Chauncey; Morgan, Rodney W.; Zawidzka, Elizabeth M.; Mertz, David; Bousley, Dick; Majchrzak, Kinga; Kryczek, Ilona; Taylor, Clarke; Van Huis, Chad; Skalitzky, Don
ABSTRACT ROR?t is the key transcription factor controlling the development and function of CD4+ Th17 and CD8+ Tc17 cells. Across a range of human tumors, about 15% of the CD4+ T cell fraction in tumor-infiltrating lymphocytes are ROR?+ cells. To evaluate the role of ROR? in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate ROR? to a greater extent than the endogenous agonist desmosterol. These ROR? agonists enhance effector function of Type 17...
Zogopoulos, Panagiotis; Korkolopoulou, Penelope; Patsouris, Efstratios; Theocharis, Stamatios
Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2). Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain. Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration. We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.
Vass, A.A.; Tyndall, R.L.; Terzaghi-Howe, P.
This application describes a bacterial preparation from Pseudomonas species isolated number s ign15 ATCC 55638 that has been exposed to gamma radiation exhibits cytotoxicity that is specific for neoplastic carcinoma cells. A method for obtaining a bacterial preparation having antitumor activity consists of suspending a bacterial isolate in media and exposing the suspension to gamma radiation. A bacterial preparation of an aged culture of an amoeba-associated bacteria exhibits anti-reverse transcriptase activity. A method for obtaining a bacterial preparation having anti-reverse transcriptase activity from an amoeba-associated bacterial isolate grown to stationary phase is disclosed
Cristea, Cecilia; Tertis, Mihaela; Galatus, Ramona
Widespread use of antibiotics has led to pollution of waterways, potentially creating resistance among freshwater bacterial communities. Microorganisms resistant to commonly prescribed antibiotics (superbug) have dramatically increased over the last decades. The presence of antibiotics in waters, in food and beverages in both their un-metabolized and metabolized forms are of interest for humans. This is due to daily exposure in small quantities, that, when accumulated, could lead to development of drug resistance to antibiotics, or multiply the risk of allergic reaction. Conventional analytical methods used to quantify antibiotics are relatively expensive and generally require long analysis time associated with the difficulties to perform field analyses. In this context, electrochemical and optical based sensing devices are of interest, offering great potentials for a broad range of analytical applications. This review will focus on the application of magnetic nanoparticles in the design of different analytical methods, mainly sensors, used for the detection of antibiotics in different matrices (human fluids, the environmental, food and beverages samples).
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.
Johari, Juliana; Huebner, Yvonne; Hull, Judith C; Dale, Jeremy W; Hughes, Michael P
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)
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.
Full Text Available Pure C-phycocyanin (C-PC was isolated from Arthronema africanumto evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL-1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability. Agarose gel electrophoresis of the genomic DNA of treated cells displayed time-and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg-1 body weight suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role.
Yuan, Jiani; Zhou, Xuanxuan; Cao, Wei; Bi, Linlin; Zhang, Yifang; Yang, Qian; Wang, Siwang
Bufalin was reported to show strong pharmacological effects including cardiotonic, antiviral, immune-regulation, and especially antitumor effects. The objective of this study was to determine the characterization, antitumor efficacy, and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity, which were prepared by FDA-approved pharmaceutical excipients. Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high-pressure homogenization method. Their mean particle sizes were 127.6 and 155.0 nm, mean zeta potentials were 2.24 and - 18.5 mV, and entrapment efficiencies were 76.31 and 78.40%, respectively. In vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that in bufalin-loaded liposomes. The cytotoxicity of blank liposomes has been found within acceptable range, whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity. In vivo pharmacokinetics indicated that bufalin-loaded PEGylated liposomes could extend or eliminate the half-life time of bufalin in plasma in rats. The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.
Zhang, Chun Li; Li, Tai Hua; Niu, Shuang Huan; Wang, Rong Fu; Fu, Zhan Li; Guo, Feng Qin; Yang, Ming
Five new organogermanium sesquioxides have been synthesized and characterized by elemental analysis and IR spectra. All the compounds were tested for antitumor activities against KB, HCT, and Bel cells in vitro. Compound 5 (gamma-thiocarbamido propyl germanium sesquioxide) showed excellent antitumor activity, and its inhibition yield to KB, HCT, and Bel cells was 92.9%, 84.9%, and 70.9%, respectively. A rapid method was described for the labeling compound 5 with (99m)Tc, and the optimum labeling conditions were investigated. The labeling yield is above 90% in pH 7.0, 20 degrees C, reaction time greater than 10 minutes, 1 mg of compound 5, and 0.075 approximately 0.1 mg of SnCl(2). The biodistribution of (99m)Tc labeled compound 5 in nude mice bearing human colonic xenografts was studied. The result showed that the tumor uptakes were 0.73, 0.97, 0.87, and 0.62 ID%/g at 1-hour, 3-hour, 6-hour, and 20-hour postinjection, respectively. T/NT (the uptake ratio for per gram of tumor over normal tissues) was 18.3 for tumor versus brain and 5.81 for tumor versus muscle at 20-hour postinjection. The tumor clearance was slow. The results showed that compound 5 may be developed to be a suitable cancer therapeutic agent.
Wu, Guixia; Li, Jing; Yue, Jinqiao; Zhang, Shuying; Yunusi, Kurexi
Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent. However, the poor aqueous solubility of luteolin limits its clinical application. In the present study, an approach towards chemoprevention was explored using liposomes to deliver luteolin, and the antitumor efficacy was investigated in colorectal carcinoma. The present findings demonstrated that luteolin was efficiently encapsulated into liposomes with an encapsulation efficiency as high as 90%. The particle size of the liposomal luteolin (Lipo-Lut) and ζ-potential were optimized. In vitro studies demonstrated that, Lipo-Lut had a significant inhibitory effect on the growth on the CT26 colorectal carcinoma cell line compared with free luteolin (Free-Lut). The in vivo study indicated that Lipo-Lut could achieve superior antitumor effects against CT26 tumor compared with luteolin alone. The present results suggested that liposome delivery of luteolin improved solubility, bioavailability and may have potential applications in chemoprevention in clinical settings. PMID:29207088
Costa, Emmanoel V; Menezes, Leociley R A; Rocha, Suellen L A; Baliza, Ingrid R S; Dias, Rosane B; Rocha, Clarissa A Gurgel; Soares, Milena B P; Bezerra, Daniel P
Zornia brasiliensis, popularly known as "urinária", "urinana", and "carrapicho", is a medicinal plant used in Brazilian northeast folk medicine as a diuretic and against venereal diseases. The aim of this study was to investigate the chemical composition and antitumor potential of the leaf essential oil of Z. brasiliensis. The essential oil was obtained by hydrodistillation using a Clevenger-type apparatus and analyzed by GC-MS and GC-FID. Its composition was characterized by the presence of trans-nerolidol, germacrene D, trans-caryophyllene, α-humulene, and farnesene as major constituents. In vitro cytotoxicity of the essential oil and some of its major constituents (trans-nerolidol, trans-caryophyllene, and α-humulene) was evaluated for tumor cell lines from different histotypes using the Alamar blue assay. The essential oil, but not the constituents tested, presented promising cytotoxicity. Furthermore, mice inoculated with B16-F10 mouse melanoma were used to confirm its in vivo effectiveness. An in vivo antitumor study showed tumor growth inhibition rates of 1.68-38.61 % (50 and 100 mg/kg, respectively). In conclusion, the leaf essential oil of Z. brasiliensis presents trans-nerolidol, germacrene D, trans-caryophyllene, α-humulene, and farnesene as major constituents and is able to inhibit cell proliferation in cultures as well as in tumor growth in mice. Georg Thieme Verlag KG Stuttgart · New York.
POYRAZ, Burcu; GÜNEŞ, Hatice; TÜL, Bahar; SERMENLİ, Hayrünisa BAŞ
Mushrooms are considered to be an important natural resource for the investigation of new compounds with antimicrobial, anti-tumor or immunomodulatory effects because of their secondary metabolites and degrading enzymes. In this study, antibacterial and antitumor potential of Cantharellus cibarius, Clitocybe geotropa, Gyromitra esculenta, Lactarius delicious, Melanoleuca exscissa, Ramaria flava, Sarcosphaera crassa, Morchella sp., Stereum hirsutum and Trametes versicolor mushrooms collected f...
Spurling, Geoffrey Kp; Del Mar, Chris B; Dooley, Liz; Foxlee, Ruth; Farley, Rebecca
Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost, and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010 and 2013. To evaluate the effects on clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. For this 2017 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4, 2017), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (2013 to 25 May 2017); Ovid Embase (2013 to 2017 Week 21); EBSCO CINAHL Plus (1984 to 25 May 2017); Web of Science (2013 to 25 May 2017); WHO International Clinical Trials Registry Platform (1 September 2017); and ClinicalTrials.gov (1 September 2017). Randomised controlled trials involving participants of all ages defined as having an RTI, where delayed antibiotics were compared to immediate antibiotics or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. We used standard Cochrane methodological procedures. Three review authors independently extracted and collated data. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information. For this 2017 update we added one new trial involving 405 participants with uncomplicated acute respiratory infection. Overall, this review included 11 studies with a total of 3555 participants. These 11 studies involved acute respiratory infections including acute otitis media (three studies
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...
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...
Shimura, K; Ito, H; Hibasami, H
On crossed immunoelectrophoresis, human serum C3 (the third component of complement) converted by antitumor polysaccharides (ATSO [antitumor polysaccharide oral], AB-P [Agaricaus blazei polysaccharide], GU-P [Grifora umbellata polysaccharide], PS-K [polysaccharide Kureha] and zymosan) moved faster than native C3, appearing as the 3rd peak. The ratio of height of the 3rd peak to the alpha 2-macroglobulin (alpha 2-M) peak was linearly proportional to the dose of ATSO. At the dose of 500 micrograms/ml antitumor polysaccharides, the ratios were higher than 0.76, and the ratios for the serum treated with polysaccharide of no antitumor activity (dextran and gum arabic) were less than about 0.52. This ratio readily determined in vivo can be used as a measure for the antitumor activity of polysaccharides.
In the past 10 years, the number of strains of Streptococcus pneumoniae and other common respiratory pathogens that are resistant to penicillin has increased. The Iowa Department of Public Health convened a multidisciplinary task force in January 1998 to develop strategies to combat antibiotic resistance in the state because they were alarmed by these reports. Within 18 months, the task force implemented statewide surveillance of resistant organisms and posted information about the surveillance on the Internet, distributed a public health guide on judicious antibiotic use and infection control measures to 7500 healthcare providers, and held a press conference to inform the public about antibiotic resistance. The task force collaborated with several major insurers in the state to profile the top prescribers of antibiotic agents in their plan. The profiling and educational interventions led to a substantial decrease in both overall antibiotic prescribing and drug costs. Other states may want to undertake similar programs to help protect their citizens from infections caused by resistant pathogens.
The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Rademacher, J; Welte, T
The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA. The fluoroketolide solithromycin should help against macrolide-resistant pathogens and has been shown to be noninferior to the fluorochinolones. The oxazolidinone tedizolid is effective against linezolid-resistant MRSA. The two cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam are not only effective against gram-negative pathogens, but they have a very broad spectrum. Due to the efficacy against extended-spectrum β‑lactamases, they can relieve the selection pressure of the carbapenems. We benefit from all new antibiotics which can take the selection pressure from other often used antibiotics. The increasing number of resistant gram-negative pathogens worldwide is alarming. Thus, focusing on the development of new drugs is extremely important.
Leyla S. Namazova-Baranova
Full Text Available The article brings up the topic not only vital and urgent for further development of modern medical science, but also affecting the interests of mankind as a whole and of every inhabitant of the Earth in particular: that is the irrational use of antibiotics and antibiotic resistance which rate is growing rapidly. We investigate the reasons for the epidemic of antibiotic resistance and discuss in detail all the necessary measures in order to cope with this problem. The shocking data on the almost universal irrational use of antibiotics by both medical workers and parents is provided. We demonstrate the microbiome changes that follow antibacterial drugs application resulting in the development of severe chronic pediatric diseases which cause severe disability or life-threatening conditions in children with long-term results in adult age. In conclusion, we summarize the evidence-based research in phytomedicine that present the phytopreparations as a serious alternative to antibiotics in a number of clinical settings.
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.
Cotten, Charles M
Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.
Childs, S J; Wood, P D; Kosola, J W
Antibiotic prophylaxis in surgery, particularly genitourinary surgery, has been controversial for years. At best, the results have been more testimonial than scientific because of the failure to observe proper experimental design. A survey of the literature indicates that antibiotic prophylaxis in genitourinary surgery probably has little influence on postoperative fever; it appears to favorably affect the incidence of postoperative bacteriuria and bacteremia in the short term without encouraging nosocomial or resistant infections. The regimen for prophylaxis must be perioperative and continued for no longer than 24 hours postoperatively. Given that antibiotic prophylaxis in elective genitourinary surgery has merit, a comparison between cefazolin and cefotaxime was undertaken. Of 160 evaluable cases, a total of 23 patients had positive cultures within the first nine days; only two occurred within the first five days. When cefazolin and cefotaxime were administered in the same dosage regimen, the infection rate for cefazolin was 19% compared with 10% for cefotaxime.
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 preventing......Endophthalmitis is one of the most feared complications after cataract surgery. The aim of this systematic review was to evaluate the effect of intracameral and topical antibiotics on the prevention of endophthalmitis after cataract surgery. A systematic literature review in the MEDLINE, CINAHL...... randomized trial and one observational study. The quality and design of the included studies were analysed using the Cochrane risk of bias tool. The quality of the evidence was evaluated using the GRADE approach. We found high-to-moderate quality evidence for a marked reduction in the risk of endophthalmitis...
Thomsen, Thomas Thyge
Multi-drug resistance to antibiotics represents a global health challenge that results in increased morbidity and mortality rates. The annual death-toll is >700.000 people world-wide, rising to ~10 million by 2050. New antibiotics are lacking, and few are under development as return on investment...... is considered poor compared to medicines for lifestyle diseases. According to the WHO we could be moving towards a post-antibiotic era in which previously treatable infections become fatal. Of special importance are multidrug resistant bacteria from the ESKAPE group (Enterococcus faecium, Staphylococcus aureus...... and toxicity by utilizing of the fruit fly Drosophila melanogaster as a whole animal model. This was carried out by testing of antimicrobial peptides targeting Gram-positive bacteria exemplified by the important human pathogen methicillin resistant S. aureus (MRSA). The peptide BP214 was developed from...
Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.
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. Copyright © 2014. Published by Elsevier Ltd.
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
Zhao, Bin; Zhang, Xiaoying
Multi-antibiotic resistance in bacterial infections is a growing threat to public health. Some experiments were carried out to study the multi-antibiotic resistance. The changes of the multi-antibiotic resistance with time were achieved by numerical simulations and the mathematical models, with the calculated temperature field, velocity field, and the antibiotic concentration field. The computed results and experimental results are compared. Both numerical simulations and the analytic models suggest that minor low concentrations of antibiotics could induce antibiotic resistance in bacteria. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The anti-tumor effect of R-Phycoerythrin (R-PE from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180 tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg-1. Simultaneously, the significant increase of superoxide dismutase (SOD activity in serum (p < 0.01 and the decrease of the malondialdehyde (MDA level in liver suggests that R-PE improved the anti-oxidant ability of the S180 tumor-bearing mice, which may related to its antitumor effect. In addition, the R-PE caused a significant increase (p < 0.05 in the spleen index and thymus index, and a significant increase (p < 0.01 in lymphocyte proliferation, NK cell kill activity and the TNF-α level in the serum of S180 tumor-bearing mice. These results strongly suggest that the antitumor effect of R-PE from Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease
Full Text Available Kai Li,1,* Yongxing Zhang,2,* Mengting Chen,1 Yangyang Hu,1 Weiliang Jiang,1 Li Zhou,1 Sisi Li,1 Min Xu,1 Qinghua Zhao,2 Rong Wan1 1Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the antitumor efficacy of doxorubicin (DOX and provide novel clinical treatment of gastric cancer, halloysite nanotubes (HNTs loaded with DOX were encapsulated by soybean phospholipid (LIP and the formed HNTs/DOX/LIP was systematically characterized via different techniques. The in vitro anticancer activity of HNTs/DOX/LIP was examined using an MTT assay. The antitumor efficacy and biocompatibility were monitored by measuring the tumor volume and assessing the blood routine and serum biochemistry using an ectopic implantation cancer model. The results show that when the concentration of HNTs was 3 mg/mL and the concentration of DOX was 1 mg/mL the optimal DOX loading efficiency was as high as 22.01%±0.43%. In vitro drug release behavior study demonstrated that HNTs/DOX/LIP shows a pH-responsive release property with fast drug release under acidic conditions (pH =5.4. MTT assays and in vivo experimental results revealed that HNTs/DOX/LIP exhibits a significantly higher inhibitory efficacy on the growth of mouse gastric cancer cells than free DOX at the same drug concentration. In addition, the life span of tumor-bearing mice in the HNTs/DOX/LIP-treated group was obviously prolonged compared with the control groups. Moreover, HNTs/DOX/LIP possessed excellent hemocompatibility as shown in the blood and histology studies. These findings indicated that the formed HNTs/DOX/LIP possesses higher antitumor efficacy and may be used as a targeted
Elaine G. Rodrigues
Full Text Available Peptides are remarkably reactive molecules produced by a great variety of species and able to display a number of functions in uni-and multicellular organisms as mediators, agonists and regulating substances. Some of them exert cytotoxic effects on cells other than those that produced them, and may have a role in controlling subpopulations and protecting certain species or cell types. Presently, we focus on antifungal and antitumor peptides and discuss a few models in which specific sequences and structures exerted direct inhibitory effects or stimulated a protective immune response. The killer peptide, deduced from an antiidiotypic antibody, with several antimicrobial activities and other Ig-derived peptides with cytotoxic activities including antitumor effects, are models studied in vitro and in vivo. Peptide 10 from gp43 of P. brasiliensis (P10 and the vaccine perspective against paracoccidioidomycosis is another topic illustrating the protective effect in vivo against a pathogenic fungus. The cationic antimicrobial peptides with antitumor activities are mostly reviewed here. Local treatment of murine melanoma by the peptide gomesin is another model studied at the Experimental Oncology Unit of UNIFESP.Peptídeos são moléculas particularmente reativas produzidas por uma grande variedade de espécies, aptos a exercer um número de funções em organismos uni-e multicelulares como mediadores, agonistas e substâncias regulatórias. Alguns deles exercem efeitos citotóxicos em células outras das que os produzem, e podem ter um papel controlando subpopulações e protegendo certas espécies ou tipos celulares. No presente, focalizamos peptídeos antifúngicos e antitumorais e discutimos alguns modelos nos quais seqüências específicas e estruturas exercem efeitos inibitórios diretos ou estimulam uma resposta imune protetora. O peptídeo letal ("killer", deduzido de um anticorpo anti-idiotípico, com várias atividades antimicrobianas bem
Li, Jia; Zhang, Kaina; Zhang, Hua
Microplastics and antibiotics are two classes of emerging contaminants with proposed negative impacts to aqueous ecosystems. Adsorption of antibiotics on microplastics may result in their long-range transport and may cause compound combination effects. In this study, we investigated the adsorption of 5 antibiotics [sulfadiazine (SDZ), amoxicillin (AMX), tetracycline (TC), ciprofloxacin (CIP), and trimethoprim (TMP)] on 5 types of microplastics [polyethylene (PE), polystyrene (PS), polypropylene (PP), polyamide (PA), and polyvinyl chloride (PVC)] in the freshwater and seawater systems. Scanning Electron Microscope (SEM) and X-ray diffractometer (XRD) analysis revealed that microplastics have different surface characterizes and various degrees of crystalline. Adsorption isotherms demonstrated that PA had the strongest adsorption capacity for antibiotics with distribution coefficient (K d ) values ranged from 7.36 ± 0.257 to 756 ± 48.0 L kg -1 in the freshwater system, which can be attributed to its porous structure and hydrogen bonding. Relatively low adsorption capacity was observed on other four microplastics. The adsorption amounts of 5 antibiotics on PS, PE, PP, and PVC decreased in the order of CIP > AMX > TMP > SDZ > TC with K f correlated positively with octanol-water partition coefficients (Log K ow ). Comparing to freshwater system, adsorption capacity in seawater decreased significantly and no adsorption was observed for CIP and AMX. Our results indicated that commonly observed polyamide particles can serve as a carrier of antibiotics in the aquatic environment. Copyright © 2018 Elsevier Ltd. All rights reserved.
Altunaiji, S; Kukuruzovic, R; Curtis, N; Massie, J
Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. Three to four review authors independently extracted data and assessed the quality of each trial. Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.
Guidugli, Fábio; Castro, Aldemar A; Atallah, Alvaro N
Leptospirosis is an infectious disease transmitted by animals. Death occurs in about five per cent of the patients. In clinical practice, doxycycline is widely used for prevention. To evaluate the effectiveness and safety of any antibiotic regimen versus placebo or other antibiotic regimens in the prophylaxis of leptospirosis. The sources used were: EMBASE, LILACS, MEDLINE, SCISEARCH, The Cochrane Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, bibliographies of published papers, and personal communication with authors. There were no language or date restrictions in any of the searches. All randomised clinical trials in which antibiotics were used as prophylactic regimen for leptospirosis. People potentially exposed to leptospirosis, such as people in endemic areas during the rainy season, health professionals and other professionals with high risk of infection. Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen). Infection (primary outcome) and adverse events (secondary outcome). Data were independently extracted and methodological quality of each trial was assessed by two reviewers as well as cross-checked. Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow-up were recorded. The results of each trial were summarised on an intention-to-treat basis in 2 x 2 tables for each outcome. Two trials comparing doxycycline with placebo met the inclusion criteria. We did not find trials comparing doxycycline versus other antibiotics, or other antibiotics versus placebo. One of the trials had excellent methodological quality. In the other trial, the allocation concealment process, generation of allocation sequence, and blinding methods were not described.Of the 1022 participants enrolled, 509 were treated with doxycycline and 513 with placebo. Of these, 940 participants were soldiers included in one trial. The patients assigned to the
Full Text Available We derive models of the effects of periodic, discrete dosing or constant dosing of antibiotics on a bacterial population whose growth is checked by nutrient-limitation and possibly by host defenses. Mathematically rigorous results providing sufficient conditions for treatment success, i.e. the elimination of the bacteria, as well as for treatment failure, are obtained. Our models can exhibit bi-stability where the infection-free state and an infection-state are locally stable when antibiotic dosing is marginal. In this case, treatment success may occur only for sub-threshold level infections.
El-Gamal, Mohammed I; Brahim, Imen; Hisham, Noorhan; Aladdin, Rand; Mohammed, Haneen; Bahaaeldin, Amany
Carbapenems are among the most commonly used and the most efficient antibiotics since they are relatively resistant to hydrolysis by most β-lactamases, they target penicillin-binding proteins, and generally have broad-spectrum antibacterial effect. In this review, we described the initial discovery and development of carbapenems, chemical characteristics, in vitro/in vivo activities, resistance studies, and clinical investigations for traditional carbapenem antibiotics in the market; imipenem-cilastatin, meropenem, ertapenem, doripenem, biapenem, panipenem/betamipron in addition to newer carbapenems such as razupenem, tebipenem, tomopenem, and sanfetrinem. We focused on the literature published from 2010 to 2016. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Azodo, C C; Ojehanon, P I
Inappropriate antibiotics prescription in dental healthcare delivery that may result in the emergence of antibiotic-resistant bacteria, is a worldwide concern. The objective of the study was to determine the antibiotics knowledge and prescription patterns among dentists in Nigeria. A total of 160 questionnaires were distributed to dentists attending continuing education courses organized by two organizations in Southern and Northern parts of Nigeria. Data analysis was done using SPSS version 17.0. A total of 146 questionnaires were returned, properly filled, out of 160 questionnaires, giving an overall response rate 91.3%. The clinical factors predominantly influenced the choice of therapeutic antibiotics among the respondents. In this study, the most commonly prescribed antibiotics among the respondents was a combination of amoxicillin and metronidazole. Of the respondents, 136 (93.2%) of them considered antibiotic resistance as a major problem in Nigeria and 102 (69.9%) have experienced antibiotics resistance in dental practice. The major reported conditions for prophylactic antibiotics among the respondents were diabetic mellitus, HIV/AIDS, history of rheumatic fever, other heart anomalies presenting with heart murmur and presence of prosthetic hip. The knowledge of adverse effects of antibiotics was greatest for tooth discoloration which is related to tetracycline. Data from this study revealed the most commonly prescribed antibiotics as a combination of amoxicillin and metronidazole. There existed gaps in prophylactic antibiotic prescription, consideration in the choice of therapeutic antibiotics and knowledge of adverse effects of antibiotics among the studied dentists.
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.
Jeong, Yong-Tae; Yang, Byung-Keun; Jeong, Sang-Chul; Kim, Sang-Min; Song, Chi-Hyun
The antitumor effect of exo-biopolymer (EXP) produced by Ganoderma applanatum was investigated using sarcoma-180 bearing mice. EXP, when administered (10-80 mg/kg body weight: BW) intraperitoneally, significantly inhibited the growth of solid tumor and increased the natural killer (NK) cell activity. A dose of 40 mg/kg BW was found to be highly effective, as it reduced the tumor formation by 39.7%, and increased the NK cell activity of splenocytes by 51.6% compared with the control group. The complement activity of EXP was increased in accordance with an increase in concentration. The phosphatase activity of macrophages was increased by 0.7-fold (200 microg/mL) compared with the control group. This EXP contained 58.9% carbohydrate and 17.1% protein. The major sugar of EXP was composed of mannose and glucose, while the protein mainly consisted of serine, glycine and aspartic acid.
Lyakhova, I A; Bryukhovetsky, I S; Kudryavtsev, I V; Khotimchenko, Yu S; Zhidkov, M E; Kantemirov, A V
Antitumor efficiency of fascaplysin synthetic derivatives (7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, and 10-bromofascaplysin) was compared out in vitro on C6 glioma cells. The cytotoxic efficiency of all tested compounds was higher than that of unsubstituted fascaplysin; 3-bromofascaplysin and 7-phenylfascaplysin exhibited the best capacity to kill glioma C6 cells. Apoptosis was the main mechanism of glioma cell death. The cytotoxic activity of these compounds increased with prolongation of exposure to the substance and increase of its concentration. Fascaplysin derivatives modified all phases of glioma cell vital cycle. The count of viable tumor cell in G0 phase remained minimum by the end of experiment under the effects of 3-bromofascaplysin and 7-phenylfascaplysin.
Mei, ChengHan; Zhou, ShunChang; Zhu, Lin; Ming, JiaXiong; Zeng, FanDian; Xu, Rong
Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC) is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX), a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.
Full Text Available Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX, a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.
A pharmacokinetic study of the antitumor drug oxoplatinum labeled with 191 Pt when agministered to control mice and mice with B-16 melanoma have shown that distribution of the drug in organs and tissues in both groups of animals is nonuniform. The drug is more tropic to the kidneys, liver, spleen, adrenals, thymus, skin and tumor. Correlation was established between the values of the coefficient ratios of differential accumulation (CDA) of the organ/blood in the f;.nal and initial periods of observation and the period of the drug half-life in the organs. The higher the CDA of the organ/blood the longer the period of the drug half-life. The excretion of the drug from the blood and most other organs is described by a bioexponential curve
David-Cordonnier, Marie-Hélène; Laine, William; Gaslonde, Thomas; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Léonce, Stéphane; Pierré, Alain; Bailly, Christian
Acronycine, a natural alkaloid originally extracted from the bark of the Australian ash scrub Acronychia baueri, has shown a significant antitumor activity in animal models. Acronycine has been tested against human cancers in the early 1980s, but the clinical trials showed modest therapeutic effects and its development was rapidly discontinued. In order to optimize the antineoplastic effect, different benzoacronycine derivatives were synthesized. Among those, the di-acetate compound S23906-1 was recently identified as a promising anticancer drug candidate and a novel alkylating agent specifically reacting with the exocylic 2-NH2 group of guanines in DNA. The study of DNA bonding capacity of acronycine derivatives leads to the identification of the structural requirements for DNA alkylation. In nearly all cases, the potent alkylating agents, such as S23906-1, were found to be much more cytotoxic than the unreactive analogs such as acronycine itself or diol derivatives. Alkylation of DNA by the monoacetate derivative S28687-1, which is a highly reactive hydrolysis metabolite of S23906-1, occurs with a marked preference for the N2 position of guanine. Other bionucleophiles can react with S23906-1. The benzacronycine derivatives, which efficiently alkylate DNA, also covalently bind to the tripeptide glutathione (GSH) but not to the oxidized product glutathione disulfide. Here we review the reactivity of S23906-1 and some derivatives toward DNA and GSH. The structure-activity relationships in the benzacronycine series validate the reaction mechanism implicating DNA as the main molecular target. S23906-1 stands as the most promising lead of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the acronycine skeleton.
E. R. Nemtsova
Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.
Zhang, Chong-Miao; Xu, Li-Mei; Wang, Xiaochang C; Zhuang, Kai; Liu, Qiang-Qiang
To evaluate the effect of ultraviolet (UV) disinfection on antibiotic-resistant Escherichia coli (E. coli). Antibiotic-resistant E. coli strains were isolated from a wastewater treatment plant and subjected to UV disinfection. The effect of UV disinfection on the antibiotic resistance profiles and the antibiotic resistance genes (ARGs) of antibiotic-resistant E. coli was evaluated by a combination of antibiotic susceptibility analysis and molecular methods. Results indicated that multiple-antibiotic-resistant (MAR) E. coli were more resistant at low UV doses and required a higher UV dose (20 mJ cm -2 ) to enter the tailing phase compared with those of antibiotic-sensitive E. coli (8 mJ cm -2 ). UV disinfection caused a selective change in the inhibition zone diameters of surviving antibiotic-resistant E. coli and a slight damage to ARGs. The inhibition zone diameters of the strains resistant to antibiotics were more difficult to alter than those susceptible to antibiotics because of the existence and persistence of corresponding ARGs. The resistance of MAR bacteria to UV disinfection at low UV doses and the changes in inhibition zone diameters could potentially contribute to the selection of ARB in wastewater treatment after UV disinfection. The risk of spread of antibiotic resistance still exists owing to the persistence of ARGs. Our study highlights the acquisition of other methods to control the spread of ARGs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Meredith, Hannah R; Srimani, Jaydeep K; Lee, Anna J; Lopatkin, Allison J; You, Lingchong
Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. Also important, however, is the fact that a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming and interpopulation interactions. These strategies can enable rapid population recovery after antibiotic treatment and provide a time window during which otherwise susceptible bacteria can acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.
... Role What CDC is Doing: AR Solutions Initiative Investing in States: Map Antibiotic Resistance Lab Network Antibiotic ... CDC and Partners Tackle Drug-Resistant TB in India Newly Reported Gene, mcr -1, Threatens Last-Resort ...
Sydenham, Rikke Vognbjerg; Plejdrup Hansen, Malene; Pedersen, Line Bjørnskov
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...... from general practice. The prescription of broad-spectrum antibiotics can cause unnecessary side effects for the individual and increases the risk of development of bacteria resistant to antibiotic treatment. Both the prescription of broad-spectrum antibiotics and the level of resistant bacteria......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...
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
9 mars 2015 ... strategy to prevent the spread of this resistance. Keywords: Staphylococci; Staphylococcus aureus; Oxacillin; Antibiotic resistance; Disc diffusion. Author Correspondence, e-mail: firstname.lastname@example.org. ICID: 1142924. Journal of Fundamental and Applied Sciences. ISSN 1112-9867. Available online at.
Pottegård, Anton; Broe, Anne; Aabenhus, Rune
Background: We aimed to describe the use of systemic antibiotics among children in Denmark. Methods: National data on drug use in Denmark were extracted from the Danish National Prescription Database. We used prescription data for all children in Denmark aged 0 to 11 years from January 1, 2000...
Bohn, Pernille; Bak, Søren A; Björklund, Erland
Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C f...
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.
Martinez-Klimova, Elena; Rodríguez-Peña, Karol; Sánchez, Sergio
Until a viable alternative can be accessible, the emergence of resistance to antimicrobials requires the constant development of new antibiotics. Recent scientific efforts have been aimed at the bioprospecting of microorganisms' secondary metabolites, with special emphasis on the search for antimicrobial natural products derived from endophytes. Endophytes are microorganisms that inhabit the internal tissues of plants without causing apparent harm to the plant. The present review article compiles recent (2006-2016) literature to provide an update on endophyte research aimed at finding metabolites with antibiotic activities. We have included exclusively information on endophytes that produce metabolites capable of inhibiting the growth of bacterial, fungal and protozoan pathogens of humans, animals and plants. Where available, the identified metabolites have been listed. In this review, we have also compiled a list of the bacterial and fungal phyla that have been isolated as endophytes as well as the plant families from which the endophytes were isolated. The majority of endophytes that produce antibiotic metabolites belong to either phylum Ascomycota (kingdom Fungi) or to phylum Actinobacteria (superkingdom Bacteria). Endophytes that produce antibiotic metabolites were predominant, but certainly not exclusively, from the plant families Fabaceae, Lamiaceae, Asteraceae and Araceae, suggesting that endophytes that produce antimicrobial metabolites are not restricted to a reduced number of plant families. The locations where plants (and inhabiting endophytes) were collected from, according to the literature, have been mapped, showing that endophytes that produce bioactive compounds have been collected globally. Copyright © 2016 Elsevier Inc. All rights reserved.
Jaruseviciene, L.; Radzeviciene-Jurgute, R.; Jurgutis, A.
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...
Elbur, Abubaker Ibrahim; M.A., Yousif; El-Sayed, Ahmed S.A.; Abdel-Rahman, Manar E.
Introduction: Surgical site infections account for 14%-25% of all nosocomial infections. The main aims of this study were to audit the use of prophylactic antibiotic, to quantify the rate of post-operative wound infection, and to identify risk factors for its occurrence in general surgery.
Ravat, François; Le-Floch, Ronan; Vinsonneau, Christophe; Ainaud, Pierre; Bertin-Maghit, Marc; Carsin, Hervé; Perro, Gérard
Infection is a major problem in burn care and especially when it is due to bacteria with hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-negative organisms, the most effective molecules are 20 years old and there is little hope of any new product available even in the distant future. Therefore, it is obvious that currently available antibiotics should not be misused. With this aim in mind, the following review was conducted by a group of experts from the French Society for Burn Injuries (SFETB). It examined key points addressing the management of antibiotics for burn patients: when to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The authors also considered antibioprophylaxis and some other key points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French guidelines for the use of antibiotics in burn patients have been designed up from this work. Copyright © 2009 Elsevier Ltd and ISBI. All rights reserved.
Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C
In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases.
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
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...... of antibiotics, as observed in heavy users, could also be due to factors related to the GP, patient and parents' expectations or the influence exerted by the pharmaceutical industry (2). This article is protected by copyright. All rights reserved....
Prakash, A S; Denny, W A; Gourdie, T A; Valu, K K; Woodgate, P D; Wakelin, L P
The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed.
limiting viral infection and therefore, would not require antibiotics. Over prescription of antibiotics increases antibiotics exposure and development of resistance among patients. There is need to evaluate empiric antibiotic prescription in order to limit ...
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
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
van Daalen, Frederike Vera; Lagerburg, Anouk; de Kort, Jaclyn; Sànchez Rivas, Elena; Geerlings, Suzanne Eugenie
No interventions have yet been implemented to improve antibiotic use on Aruba. In the Netherlands, the introduction of an antibiotic checklist resulted in more appropriate antibiotic use in nine hospitals. The aim of this study was to introduce the antibiotic checklist on Aruba, test its
Full Text Available Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.
Luckhaupt, H; Rose, K G
For the otolaryngologist (ENT specialist), too, antibiotics are among the most frequently prescribed drugs. This article gives the essential fundamentals for the antibiotic treatment of patients with restricted kidney functions, as well as advice for antibiotic therapy in clinics and in medical practice.
Schäberle, Till F; Hack, Ingrid M
Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
Hulscher, M.E.J.L.; Meer, J.W.M. van der; Grol, R.P.T.M.
Antibiotics are an extremely important weapon in the fight against infections. However, antimicrobial resistance is a growing problem. That is why the appropriate use of antibiotics is of great importance. A proper analysis of factors influencing appropriate antibiotic use is at the heart of an
Countries have come to place heavy reliance on antibiotics, a phenomena that has contributed to widespread resistant bacteria. Unless antibiotic prescribing patterns are kept in check, the spread of resistant bacteria will lead to a proliferation of dreadful diseases. In this study, antibiotic prescribing patterns at Van Velden ...
Veloo, A. C. M.; Seme, K.; Raangs, Gerwin; 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
Full Text Available The current communication, based upon the previous published papers in various scientific web-based journals, states the scenario of over-the-counter sales of antibiotics, including many other factors, that enhance people practice antibiotic self-medication world-wide, which in the developed countries the situation is little different having some resolution with the antibiotic self-medication problems. This paper also states about the prudent use of antibiotics through medical supervision and prescription in order to combat the unwanted antibiotic side effects including emergence of antibiotic resistant bacteria from antibiotic misusage.
Malik, M.A.; Shaukat, G.A.; Ahmed, M.S.
Three types of antibiotics S, X and F characteristically bioactive against staphylococcic, xanthomonas and fungi are elaborated by Bacillus Subtilis AECL 69 when grown in molasses peptone malt extract sucrose. No antibiotic production was observed when molasses was omitted from the growth medium. A mineral salt mixture was devised that could replace molasses and restore the production of antibiotics. Influence of various carbohydrates on the production of antibiotics was also studied. Mannose and mannitol had inhibitory effect on the antibiotic production. (author)
Kim, Jeongjin; Jo, Ara; Chukeatirote, Ekachai; Ahn, Juhee
Background Bacteria treated with different classes of antibiotics exhibit changes in susceptibility to successive antibiotic treatments. This study was designed to evaluate the influence of sequential antibiotic treatments on the development of antibiotic resistance in Klebsiella pneumoniae associated with ?-lactamase and efflux pump activities. Methods The antibiotic susceptibility, ?-lactamase activity, and efflux activity were determined in K. pneumoniae grown at 37??C by adding initial (0...
Vishwambhar V. Bhandare; Sandip Mahadev Chavre
Rhizosphere soil samples were preferred as it contains most of the prospective antibiotic producers. In an attempt to screen out new potent antibiotic producers from soil, the Rhizobium species was isolated. Antibiotic produced by shake flask culture is found to be effective against both gram positive and gram negative organisms. This product was found to be a very promising antibiotic when assayed biologically. UV treatment showed positive effect on antibiotic production. The molecular struc...
Worthington, Roberta J; Melander, Christian
β-Lactam antibiotics are one of the most important antibiotic classes but are plagued by problems of resistance, and the development of new β-lactam antibiotics through side-chain modification of existing β-lactam classes is not keeping pace with resistance development. In this JOCSynopsis, we summarize small molecule strategies to overcome resistance to β-lactam antibiotics. These approaches include the development of β-lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms.
Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua
Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775
Sun, Xiaobo; Zhao, Chen; Pan, Wei; Wang, Jinping; Wang, Weijun
In this paper, the structure difference between the polysaccharides isolated from fruit bodies (FGAP) and submerged fermentation system (SGAP) of Ganoderma applanatum was investigated by means of GPC, HPLC and IR, respectively. And their antitumor activities were evaluated against Sarcoma 180 in vivo. The results showed that FGAP and SGAP were typical polysaccharides with different molecular weights, monosaccharide components, and functional groups. Closely related to the distinct structures, FGAP exhibited a better antitumor activity than SGAP. Moreover, since FGAP contained carboxylate groups rather than SGAP, such groups were chemically introduced into SGAP (CSGAP) by carboxymethylation in order to identify their contribution to antitumor activity. The results demonstrated that the inhibition of CSGAP against Sarcoma 180 in vivo was significantly enhanced by comparison to the native SGAP and even higher than that of FGAP, suggesting that the carboxylate groups played a major role in antitumor activity of G. applanatum polysaccharide. Copyright © 2015 Elsevier Ltd. All rights reserved.
Macy, Eric; Romano, Antonino; Khan, David
Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Şincai, Mariana; Gângǎ, Diana; Bica, Doina; Vékás, Ladislau
The endocytosis of nanosized magnetic particles by tumor cells led to numerous tests to establish the use of this phenomenon in antitumor therapy. The direct antitumor effect of a biocompatible cobalt-ferrite-based magnetic fluid directly inoculated in bitch mammary tumors was studied. A direct correlation between tumor cell lysis and cobalt ferrite was established in tumors. Massive endocytosis of magnetic particles was observed 1 h after the contact of magnetic fluid with tumor cells.
Vishnu, Prakash; Colon-Otero, Gerardo; Kennedy, Gregory T; Marlow, Laura A; Kennedy, William P; Wu, Kevin J; Santoso, Joseph T; Copland, John A
The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination. HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing. The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines. Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides 'proof-of-principle' for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. Copyright © 2011 Elsevier Inc. All rights reserved.
Andreani, Aldo; Burnelli, Silvia; Granaiola, Massimiliano; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla; Calonghi, Natalia; Cappadone, Concettina; Farruggia, Giovanna; Zini, Maddalena; Stefanelli, Claudio; Masotti, Lanfranco; Radin, Norman S; Shoemaker, Robert H
The synthesis of new antitumor 6-substituted imidazothiazole guanylhydrazones is described. Moreover, a series of compounds with a different basic chain at the 5 position were prepared. Finally, the replacement of the thiazole ring in the imidazothiazole system was also considered. All the new compounds prepared were submitted to the NCI cell line screen for evaluation of their antitumor activity. A few selected compounds were submitted to additional biological studies concerning effects on the cell cycle, apoptosis, and mitochondria.
Yang, Gu-Liang; Zhao, Sheng-Fang; Chen, Nian-You; Li, Shiming
A novel fluoroporphyrin-anthraquinone hybrid with dipeptide link and its metal complexes were synthesized and evaluated for anti-proliferation activity in human cancer cell line HeLa. The preliminary results demonstrated that all the compounds showed moderate to excellent antitumor activities. Among the active compounds, compound 3 which contains fluorinated porphyrin-anthraquinone and zinc ion exhibited the highest potency with IC50 value of 8.83 µM, indicating that it was a promising antitumor candidate.
Full Text Available Biofilms give to bacteria micro-environmental benefits; confers protection against antimicrobials. Bacteria have antibiotic resistance by conventional and unusual mechanisms leading to delayed wound healing, to increase recurrent chronic infections and nosocomial contamination of medical devices. Objective: This narrative review aims to introduce the characteristics of Bacteria-biofilms, antimicrobial resistance mechanisms and potential alternatives for prevention and control of its formation. Methods: Search strategy was performed on records: PubMed / Medline, Lilacs, Redalyc; with suppliers such as EBSCO and thesaurus MeSH and DeCS. Conclusions: Knowledge and research performance of biofilm bacteria are relevant in the search of technology for detection and measuring sensitivity to antibiotics. The identification of Bacterial-biofilms needs no-traditional microbiological diagnosis.
Qvist, N; Christiansen, H.M.; Ehlers, D
The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greate...... of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine....
The administration of IFN-containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing or antitumor activities of the compound were detected. Cytotoxic activities were detected in peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, no antitumor activity of Ge-sera was observed. However, Ge-132 antitumor activity was observed in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell-depleted mice. Therefore, a part of the antitumor activity of Ge-132 appears to be expressed as follows: Ge-132 stimulates T-cells to produce circulating lymphokine(s) which are inactivated by anti-IFN gamma treatment; activated M phi are generated from resting M phi by these lymphokine(s); the transplanted tumors are inhibited by these M phi.
Li, Yuli; Shen, Guobo; Nie, Wen; Li, Zhimian; Sang, Yaxiong; Zhang, Binglan; Wei, Yuquan
Lipopolysaccharide (LPS) is a major component of the outer surface membrane of Gram-negative bacteria which has been proved an effective immune enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells that stimulated by LPS in mouse xenografts models. Tumor cells were irradiated after stimulation with 1 μg/mL LPS for 48 h. The C57BL/6 mice were immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of lymphocytes of immunized mice was investigated. The cytotoxicity of spleen lymphocytes from immunized mice was determined by a standard (51)Cr-release assay. The roles of immune cell subsets in anti-tumor activity were assessed by injected intraperitoneally with monoclonal antibodies. We observed that the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger protective anti-tumor immunity than other controls. Adoptive transfer of lymphocytes of immunized mice showed that the cellular immune response was involved in the anti-tumor effect. And this effect was achieved by activation of antigen-specific CD8(+) T cell response and reduction of myeloid-derived suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of immune cell subsets and flow cytometry analysis. In summary, our study showed that stimulation of LPS was able to enhance anti-tumor immunity of vaccination with tumor cells after irradiation treatment, which might be a new strategy for cancer therapy.
Bal, Abhijit M; Gould, Ian M
Antimicrobial stewardship is now recognized as a formal strategy for curbing the upward trend in antibiotic resistance. Literature on antimicrobial stewardship has focused on areas of strategic importance and operational delivery. A number of barriers have been recognized in the implementation of successful programs. These include lack of physician participation, lack of diagnostic facility, absence of formal mechanism of data collection, variation between countries, and lack of cooperative strategies. In this review, we suggest strategies to overcome these barriers. In the last few years, it has been recognized that an executive program is necessary for successful implementation of strategies to control the growing antibiotic resistance. Efforts have been made at higher levels of government through organizations such as the European Centre for Disease Prevention and Control. The need for community healthcare involvement has also been recognized. At a local level, strategies to promote cooperation between various committees (e.g. infection control and antimicrobial management teams) have been proposed and adopting antibiotic care bundles as part of patient safety and healthcare is being explored. We suggest that executive level planning, local cooperation, sustained education, emphasis on de-escalation, and use of care bundles could stem the tide of growing resistance.
Moghadam, Ali; Niazi, Ali; Afsharifar, Alireza; Taghavi, Seyed Mohsen
In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents. PMID:27459300
Full Text Available In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents.
Xu, Zhong; Wang, Yemin; Chater, Keith F.; Ou, Hong-Yu; Xu, H. Howard; Deng, Zixin
ABSTRACT Gram-positive Streptomyces bacteria produce thousands of bioactive secondary metabolites, including antibiotics. To systematically investigate genes affecting secondary metabolism, we developed a hyperactive transposase-based Tn5 transposition system and employed it to mutagenize the model species Streptomyces coelicolor, leading to the identification of 51,443 transposition insertions. These insertions were distributed randomly along the chromosome except for some preferred regions associated with relatively low GC content in the chromosomal core. The base composition of the insertion site and its flanking sequences compiled from the 51,443 insertions implied a 19-bp expanded target site surrounding the insertion site, with a slight nucleic acid base preference in some positions, suggesting a relative randomness of Tn5 transposition targeting in the high-GC Streptomyces genome. From the mutagenesis library, 724 mutants involving 365 genes had altered levels of production of the tripyrrole antibiotic undecylprodigiosin (RED), including 17 genes in the RED biosynthetic gene cluster. Genetic complementation revealed that most of the insertions (more than two-thirds) were responsible for the changed antibiotic production. Genes associated with branched-chain amino acid biosynthesis, DNA metabolism, and protein modification affected RED production, and genes involved in signaling, stress, and transcriptional regulation were overrepresented. Some insertions caused dramatic changes in RED production, identifying future targets for strain improvement. IMPORTANCE High-GC Gram-positive streptomycetes and related actinomycetes have provided more than 100 clinical drugs used as antibiotics, immunosuppressants, and antitumor drugs. Their genomes harbor biosynthetic genes for many more unknown compounds with potential as future drugs. Here we developed a useful genome-wide mutagenesis tool based on the transposon Tn5 for the study of secondary metabolism and its
Ito, Hisao; Hashimoto, Shozo
The anti-tumor activity of direct current combined with radiation was studied. The experiments were performed with fibrosarcomas (FSA, NFSA) syngenetic to C3H mice. Direct current (0.6mA, 120min) alone was effective to reduce the tumor sizes, but could not cure the tumors. When the direct current therapy (DC therapy) was combined with radiation the DC therapy following radiation was more effective than that before radiation. Using TCD 50 assay, the DC therapy enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.2. However, tumor control rates by the combination therapy were more improved at the smaller doses of radiation than at the larger ones. When the single DC therapy (0.6mA, 120min) was applied immediately after the first radiation of fractionated one the combination therapy still showed the enhanced effect. However, both DC therapy and the radiation therapy were divided in three fractions, and the DC therapy (0.6mA, 40min) was applied after each radiation. Tumor growth retardation by the combination therapy was no different from that by radiation alone. This result suggests that there might be a minimum required dose of coulombs to show the effect of the combination therapy. (author)
Full Text Available Blueberries (Vaccinium spp. are rich in bioactive compounds. However, the biological activity of polysaccharides from blueberry has not been reported so far. This study evaluated the anti-tumor and immunological activities of a polysaccharide (BBP3-1 from blueberry in S180-bearing mice. The experimental results indicated that BBP3-1 (100 mg·kg−1·d−1 inhibited the tumor growth rate by 73.4%. Moreover, this group, compared with the model control, had shown an effect of increasing both the spleen and thymus indices (p < 0.05, increasing phagocytosis by macrophages (p < 0.05, boosting the proliferation and transformation of lymphocytes (p < 0.01, promoting the secretion of TNF-α, IFN-γ, and IL-2 (p < 0.05 and improving NK cell activity (p < 0.01. From this study, we could easily conclude that BBP3-1 has the ability to inhibit tumor progression and could act as a good immunomodulator.
Qin, Xu-Jie; Yu, Qian; Yan, Huan; Khan, Afsar; Feng, Mi-Yan; Li, Pan-Pan; Hao, Xiao-Jiang; An, Lin-Kun; Liu, Hai-Yang
Psidium guajava L., a species native to South America, has been widely cultivated in the tropical and subtropical areas of China for its popular fruits. The preliminary analysis by liquid chromatography-ultraviolet (LC-UV) indicated the presence of meroterpenoids in the fruits of P. guajava (guava). Subsequent fractionation of the petroleum ether extract resulted in the identification of two new meroterpenoids, psiguajavadials A (1) and B (2), together with 14 previously described meroterpenoids (3-16). Their structures were fully elucidated by comprehensive spectroscopic techniques and theoretical calculations. All of the meroterpenoids showed cytotoxicities against five human cancer cell lines, with guajadial B (12) being the most effective having an IC 50 value of 150 nM toward A549 cells. Furthermore, biochemical topoisomerase I (Top1) assay revealed that psiguajavadial A (1), psiguajavadial B (2), guajadial B (12), guajadial C (14), and guajadial F (16) acted as Top1 catalytic inhibitors and delayed Top1 poison-mediated DNA damage. The flow cytometric analysis indicated that the new meroterpenoids psiguajavadials A (1) and B (2) could induce apoptosis of HCT116 cells. These data suggest that meroterpenoids from guava fruit could be used for the development of antitumor agents.
Full Text Available Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity and antiherpetic activity. MTT (Tetrazolium blue and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2. The 50% cytotoxic concentration (CC50 and the 50% inhibitory concentration of the viral effect (EC50 for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50. These species are good candidates for further activity-monitored fractionation to identify active principles.
Lee, K T; Choi, J H; Kim, D H; Son, K H; Kim, W B; Kwon, S H; Park, H J
To search for cytotoxic components from Allium victorialis, MTT assays on each extract and an isolated component, gitogenin 3-O-lycotetroside, were performed against cancer cell lines. Cytotoxicities of most extract were shown to be comparatively weak, though IC50 values of CHCl3 fraction was found to be organosulfuric flavours were predictable by GC-MS performance. The most abundant peak was revealed to be 2-vinyl-4H-1,3-dithiin (1) by its mass spectrum. Further, this extract showed significant cytotoxicities toward cancer cell lies. Silica gel column chromatography of the n-butanol fraction led to the isolation of gitogenin 3-O-lycotetroside (3) along with astragalin (4) and kaempferol 3, 4'-di-O-beta-D-glucoside (5). This steroidal saponin exhibited significant cytotoxic activities (IC50, 6.51-36.5 microg/ml) over several cancer cell lines. When compound 3 was incubated for 24 h with human intestinal bacteria, a major metabolite was produced and then isolated by silica gel column chromatography. By examining parent- and prominent ion peak in FAB-MS spectrum of the metabolite, the structure was speculated not to be any of prosapogenins of 3, suggesting that spiroketal ring were labile to the bacterial reaction. These suggest that disulfides produced secondarily are the antitumor principles.
Gao, Yuxiu; Shan, Ning; Zhao, Cheng; Wang, Yunhai; Xu, Fuliang; Li, Jiacun; Yu, Xiaoqian; Gao, Lifeng; Yi, Zhengjun
Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Because transforming growth factor-beta (TGF-β) could increase survival of ovarian cancer cells in the presence of cisplatin, we conducted a preclinical study of the antitumor effects of the TGF-β type I (TβRI) and type II (TβRII) kinase inhibitor LY2109761 in combination with cisplatin. SKOV3, OV-90 and SKOV3(DDP) cells were treated with LY2109761, and/or cisplatin, and cell viability, apoptosis mRNA and protein expression levels were then evaluated. Furthermore, the efficacy of LY2109761 combined with cisplatin was further examined in established xenograft models. LY2109761 was sufficient to induce spontaneous apoptosis of ovarian cancer cells. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in both parental and cisplatin resistant ovarian cancer cells. LY2109761 significantly increased apoptotic cell death in cisplatin-resistant cells. Combination treatment of LY2109761 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established parental and cisplatin resistant ovarian cancer xenograft models. Chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients.
Jennie B. Altman
Full Text Available Natural killer T (NKT cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies.
Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya; Amarasiriwardena, Chitra J; Lupoli, Nicola
The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC 50 = 0.77 ± 0.11 μM comparable to that of free cisplatin (IC 50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.
Pruden, Amy; Larsson, D.G. Joakim; Amézquita, Alejandro
Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic resistance...... of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little...... associated with antibiotic resistance strongly indicate the need for action....
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......, 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...
Agnihotry, Anirudha; Fedorowicz, Zbys; van Zuuren, Esther J; Farman, Allan G; Al-Langawi, Jassim Hasan
Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for emergency dental care. Apart from removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling into the tooth, removing the inflamed pulp (nerve) and cleaning the root canal. However, a significant number of dentists continue to prescribe antibiotics to stop the pain of irreversible pulpitis.This review updates the previous version published in 2013. To assess the effects of systemic antibiotics for irreversible pulpitis. We searched the Cochrane Oral Health Group's Trials Register (to 27 January 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 12); MEDLINE via Ovid (1946 to 27 January 2016); EMBASE via Ovid (1980 to 27 January 2016), ClinicalTrials.gov (to 27 January 2016) and the WHO International Clinical Trials Registry Platform (to 27 January 2016). There were no language restrictions in the searches of the electronic databases. Randomised controlled trials which compared pain relief with systemic antibiotics and analgesics, against placebo and analgesics in the acute preoperative phase of irreversible pulpitis. Two review authors screened studies and extracted data independently. We assessed the quality of the evidence of included studies using GRADEpro software. Pooling of data was not possible and a descriptive summary is presented. One trial assessed at low risk of bias, involving 40 participants was included in this update of the review. The quality of the body of evidence was rated low for the different outcomes. There was a close parallel distribution of the pain ratings in both the intervention and placebo groups over the seven-day study period. There was insufficient evidence to claim or refute a benefit for penicillin for pain intensity. There was no significant difference in the mean total number of ibuprofen tablets over the
Full Text Available The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo-expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo-expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.
Bulajić Snežana; Mijačević Zora; Savić-Radovanović Radoslava
Knowledge on the antibiotic resistance of lactic acid bacteria is still limited, possibly because of the large numbers of genera and species encountered in this group, as well as variances in their resistance spectra. The EFSA considers antibiotic resistances, especially transferable resistances, an important decision criterion for determining a strain's QPS status. There are no approved standards for the phenotypic or genotypic evaluation of antibiotic resistances in food isolat...
Chen, Qing-Lin; Li, Hu; Zhou, Xin-Yuan
Landfills are so far the most common practice for the disposals of municipal solid waste (MSW) worldwide. Since MSW landfill receives miscellaneous wastes, including unused/expired antibiotics and bioactive wastes, it gradually becomes a huge potential bioreactor for breeding antibiotic resistance...... be the potential hosts of ARGs. These findings provide evidence that groundwater near MSW landfill is an underappreciated hotspot of antibiotic resistance and contribute to the spread of ARGs via the flowing contaminated groundwater....
John B. Horowitz; H. Brian Moehring
Initially, economic development increases resistance because migration of people to urban areas in developing countries increases incomes, crowding and the use of antibiotics. Also, developing countries often don't require prescriptions or distribute high quality antibiotics. In developed countries, antibiotic resistance often falls or there is a decline in the rate of growth of resistance because infections decline with improvements in water quality, sanitation, housing and nutrition. Howeve...
Yousuf, Waqas; Khan, Moiz; Mehdi, Hasan; Mateen, Sana
Introduction. The aim of our study is to assess the need for postoperative antibiotics following simple exodontia and determine its role in minimizing patient discomfort and postoperative complications. Material and Methods. All the patients undergoing simple extractions were grouped into two categories: Group 1, patients receiving antibiotics, and Group 2, patients receiving no antibiotics. Patients were recalled on the sixth day to assess postoperative complications. On recall, patients wer...
Qvist, N; Christiansen, H.M.; Ehlers, D
than 10(5) colonies per ml urine); 6 patients (13.3%) in the cefotaxime group had postoperative infections during hospital stay as compared to 8 patients (18.6%) in the control group (0.5 greater than p greater than 0.3). Those in the cefotaxime group who had infections were tested for resistance...... of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine....
Pan, Qunwen; Chen, Meizhen; Li, Juan; Wu, Yan; Zhen, Chao; Liang, Bin
The anti-tumor effect of R-Phycoerythrin (R-PE) from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180) tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT) significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg⁻¹. Simultaneously, the significant increase of superoxide dismutase (SOD) activity in serum (p Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease gene expression and TNF-α secretion.
Paraskar, Abhimanyu; Soni, Shivani; Roy, Bhaskar; Papa, Anne-Laure; Sengupta, Shiladitya
Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However, the formulation of platinum chemotherapeutics in nanoparticles has been a challenge arising from their physicochemical properties. There are only a few reports describing oxaliplatin nanoparticles. In this study, we derivatized the monomeric units of a polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum (II) through a novel monocarboxylato and O → Pt coordination linkage. At a specific polymer to platinum ratio, the complex self-assembled into a nanoparticle, where the polymeric units act as the leaving group, releasing DACH–platinum in a sustained pH-dependent manner. Sizing was done using dynamic light scatter and electron microscopy. The nanoparticles were evaluated for efficacy in vitro and in vivo. Biodistribution was quantified using inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). The PIMA–GA–DACH–platinum nanoparticle was found to be more active than free oxaliplatin in vitro. In vivo, the nanoparticles resulted in greater tumor inhibition than oxaliplatin (equivalent to 5 mg kg −1 platinum dose) with minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential tumor accumulation of platinum with reduced biodistribution to the kidney or liver following PIMA–GA–DACH–platinum nanoparticle administration as compared with free oxaliplatin. These results indicate that the rational engineering of a novel polymeric nanoparticle inspired by the bioactivation of oxaliplatin results in increased antitumor potency with reduced systemic toxicity compared with the parent cytotoxic. Rational design can emerge as an exciting strategy in the synthesis of nanomedicines for cancer chemotherapy. (paper)
Stigter, M.; Bezemer, J.M.; de Groot, 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
McNulty, Cliodna A M
On 18 November 2012, the UK will once again support the annual European Antibiotic Awareness Day (EAAD). In particular, hospitals will be asked to promote the Start Smart-Then Focus guidance for hospitals launched in 2011, while the Royal College of General Practitioners will publish the TARGET Antibiotics toolkit on their web site. TARGET (Treat Antibiotics Responsibly, Guidance, Education, Tools) emphasizes the need for both primary care staff and the public to use antibiotics responsibly, and provides guidance, education and tools. The web site has been developed by a multiprofessional group and hosts national antibiotic guidance, an antibiotic app, leaflets designed to be shared by patients during consultations, a presentation for clinicians, an interactive self-assessment tool, audit tools, posters and videos for the waiting room and links to other materials. The EAAD is still very relevant and worth promoting enthusiastically through all clinical professionals in an effort to encourage responsible use of antibiotics and thereby control antibiotic resistance.
Kawakami, Y; Matsuwaka, S; Otani, T; Kondo, H; Nakamura, S
A new antifungal antibiotic, named ileumycin, was isolated from culture broth of streptomyces H 698-SY2, which was identified as S. lavendulae. The antibiotic was recovered from the culture filtrate by adsorption on Amberlite XAD-II and elution with aqueous methanol and was further purified by ion-exchange column chromatography on SE-cellulose and followed by partition chromatography on silica gel. The antibiotic was named ileumycin, because isoleucine was detected in the acid hydrolyzate of the antibiotic. Ileumycin exhibited antimicrobial activity against only a few species of fungi.
Berzanskyte, Ausra; Valinteliene, Rolanda; Haaijer-Ruskamp, Flora M; Gurevicius, Romualdas; Grigoryan, Larissa
Excessive and not always proper use of antibiotic give rise to numerous problems, of which antimicrobial resistance, currently cause for worldwide concern, is the major one. Few single studies of antibiotic use have been carried out in some countries. This study was performed to estimate the prevalence of antibiotic use in the general population of Lithuania with special interest in self-medication with antibiotics and sources of their acquisition. Structured questionnaires on antibiotic use during the last 12 months were mailed to randomly selected adults and 746 of them were finally analyzed. It was found that 39.9% of respondents reported antibiotic use during the last 12 months preceding the study and 53.2% of those used them in self-medication. In general, 22.0% (95%CI: 19.1-25.1) of respondents used antibiotics without prescription, whereas 45.0% (95%CI: 41.3-48.7) of them used antibiotics for intended self-administration. Adjustment for all the factors revealed the impact of the occupation, place of residence and presence of chronic disease on self-medication with antibiotics. Representatives of managerial, executive and professional occupations used non-prescribed antibiotics 8.38 times more often (95% CI: 1.76-39.91, p = 0.01) than retired people. Healthy people showed the tendency to self-medication 2.04 times more frequently than those with chronic diseases (95%CI: 1.11-3.75, p = 0.02). Rural people used non-prescribed antibiotics 1.79 times more often than inhabitants of urban areas (95%CI: 1.00-3.18, p = 0.049). Community pharmacies proved to be the most frequent (86.0%) source of over-the-counter antibiotics. Tonsillitis, bronchitis, and upper respiratory infections were the major reasons for self-medication with antibiotics. The high prevalence of self-medication with antibiotics was found in Lithuania. The study indicated the need for more strict control of antibiotic sales and promotion of education of the correct use of antibiotic among Lithuanian
Harbarth, S; Theuretzbacher, U; Hackett, J
The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public-private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: email@example.com.
Kitaoka, Maya; Miyata, Sarah T; Unterweger, Daniel; Pukatzki, Stefan
As the causative agent of cholera, the bacterium Vibrio cholerae represents an enormous public health burden, especially in developing countries around the world. Cholera is a self-limiting illness; however, antibiotics are commonly administered as part of the treatment regimen. Here we review the initial identification and subsequent evolution of antibiotic-resistant strains of V. cholerae. Antibiotic resistance mechanisms, including efflux pumps, spontaneous chromosomal mutation, conjugative plasmids, SXT elements and integrons, are also discussed. Numerous multidrug-resistant strains of V. cholerae have been isolated from both clinical and environmental settings, indicating that antibiotic use has to be restricted and alternative methods for treating cholera have to be implemented.
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.
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Antibiotics as preservatives. 114.10... BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use as... section. (a) When an antibiotic or combination of antibiotics, with or without a fungistat is to be used...
Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa
Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.
We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation of the efficacy of antibiotics and to stabilization of antibiotic-susceptible bacterial ecosystems should be global goals. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.
Buul, L.W. van; Steen, J.T. van der; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Greeff, S.C. de; Natsch, S.; Sloane, P.D.; Zimmerman, S.; Twisk, J.W.R.; Veenhuizen, R.B.; Hertogh, C.M.P.M.
Objectives: To evaluate the effect of tailored interventions on the appropriateness of decisions to prescribe or withhold antibiotics, antibiotic use and guideline-adherent antibiotic selection in nursing homes (NHs). Methods: We conducted a quasi-experimental study in 10 NHs in the Netherlands. A
Buul, L.W. van; Steen, J.T. van der; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.; Greeff, S.C. de; Natsch, S.S.; Sloane, P.D.; Zimmerman, S.; Twisk, J.W.R.; Veenhuizen, R.B.; Hertogh, C.M.
OBJECTIVES: To evaluate the effect of tailored interventions on the appropriateness of decisions to prescribe or withhold antibiotics, antibiotic use and guideline-adherent antibiotic selection in nursing homes (NHs). METHODS: We conducted a quasi-experimental study in 10 NHs in the Netherlands. A
van Buul, L.W.; van der Steen, J.T.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; de Greeff, S.C.; Natsch, S.; Sloane, P.D.; Zimmerman, S.; Twisk, J.W.R.; Veenhuizen, R.B.; Hertogh, C.M.P.M.
Objectives: To evaluate the effect of tailored interventions on the appropriateness of decisions to prescribe or withhold antibiotics, antibiotic use and guideline-adherent antibiotic selection in nursing homes (NHs). Methods: We conducted a quasi-experimental study in 10 NHs in the Netherlands. A
Full Text Available Objective: To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform and n-hexane extracts of Hippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens with three different concentrations of test samples (10, 100 and 1 000 mg/L. Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8% was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated in n-hexane extract. The difference in tumor and cell inhibition (% may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions: Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.
Zong Sheng eGuo
Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.
Jeyamogan, Shareni; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah
Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need for newer and more powerful anti-tumor agents. The search for new anti-tumor compounds originating from natural resources is a promising research area. Animals living in polluted environments are a potent source of anti-tumor agents. Under polluted milieus, species such as crocodiles, feed on rotten meat, are exposed to heavy metals, endure high levels of radiation, and are among the very few species to survive the catastrophic Cretaceous-Tertiary extinction event with a prolonged lifespan. Thus, it is reasonable to speculate that animals such as crocodiles have developed mechanisms to defend themselves against cancer. The discovery of antitumor activity in animals such as crocodiles, whales, sharks, etc. will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor compound(s) that may also overcome current drug resistance. Nevertheless, intensive research in the next few years will be required to realize these expectations.
Lv, Chao; Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Chuang; Fang, Ting; Yang, Pei-Ming; Wu, Tong; Zhou, Yu-Dong; Nagle, Dale G; Zhang, Wei-Dong
Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.
Gambinossi, F.; Mecheri, B.; Caminati, G.; Nocentini, M.; Puggelli, M.; Gabrielli, G
We studied the interactions of tetracycline (TC) antibiotic molecules with phospholipid monolayers with the two-fold aim of elucidating the mechanism of action and providing a first step for the realization of bio-mimetic sensors for such drugs by means of the Langmuir-Blodgett technique. We examined spreading monolayers of three phospholipids in the presence of tetracycline in the subphase by means of surface pressure-area and surface potential-area isotherms as a function of bulk pH. We selected phospholipids with hydrophobic chains of the same length but polar head groups differing either in dimensions and protonation equilibria, i.e. dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE) and dipalmitoylphosphatidic acid (DPPA). The interaction of tetracycline with the three phospholipids was found to be highly dependent on the electric charge of the antibiotic and on the ionization state of the lipid. Significant interactions are established between the negatively charged form of dipalmitoylphosphatidic acid and the zwitterionic form of tetracycline. The drug was found to migrate at the interface where it is adsorbed underneath or/and among the head groups, depending on the surface pressure of the film, whereas penetration through the hydrophobic layer was excluded for all the three phospholipids.
Full Text Available Antibiotic resistance has become an urgent and global issue, with 700,000 deaths attributable to multidrug-resistance occurring each year worldwide. The overuse of antibiotics, both in animal industry and in clinical settings, and the generated selective pressure, are the main factors implicated in the emergence of resistant strains. The Centers for Disease Control and Prevention (CDC have pointed out that more than half of hospital patients receive an antibiotic during their stay, and nearly a third receive a broad-spectrum antibiotic. In neonatal units, previous antibiotic exposure to third-generation cephalosporin and carbapenem were identified as independent risk factors for infection caused by multi-drug resistant strains. While resistant ‘superbugs’ emerge, the arsenal to fight these microorganisms is progressively shrinking, as the number of newly discovered antibiotics approved by the Food and Drug administration each year is dropping. In face of global spread of antibiotic resistance and of the limited development of new drugs, policies and rules are under study by agencies (CDC, World Health Organization and governments, in order to: i facilitate and foster the discovery of new antibiotic compounds; ii develop new, alternative therapies able to potentiate or modulate the host immune response or to abrogate the resistance and virulence factors in the microorganisms; and iii prevent the emergence of resistance through antibiotic stewardship programs, educational programs, and reduction of antibiotic use in livestock; the field of neonatal medicine will need its own, newborn-tailored, antibiotic stewardship programs to be implemented in the NICUs. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai
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.
Cohen, Margot E; Salmasian, Hojjat; Li, Jianhua; Liu, Jianfang; Zachariah, Philip; Wright, Jason D; Freedberg, Daniel E
Antibiotic-resistant infections have high rates of morbidity and mortality, and exposure to antibiotics is the crucial risk factor for development of antibiotic resistance. If surgical antibiotic prophylaxis (SAP) increases risk for antibiotic-resistant infections, prophylaxis may cause net harm, even if it decreases overall infection rates. This retrospective cohort study included adults who underwent elective surgical procedures and developed infections within 30 postoperative days. Procedures from multiple disciplines were included if SAP was considered discretionary by current guidelines. Postoperative antibiotic-resistant infections were defined as positive culture results from any site within 30 postoperative days, showing intermediate or nonsusceptibility across 1 or more antibiotic classes. Surgical antibiotic prophylaxis included use of antibiotics within any class and at any dose from 1 hour before first incision until the end of the operation. Among 689 adults with postoperative infections, 338 (49%) had postoperative resistant infections. Use of SAP was not associated with postoperative antibiotic-resistant infections (odds ratio [OR] 0.99; 95% CI 0.67 to 1.46). This result remained robust when the SAP definition was extended to antibiotics given within 4 hours before first incision (OR 0.94; 95% CI 0.63 to 1.40) and when the follow-up window was narrowed to 14 days (OR 0.82; 95% CI 0.50 to 1.34). Previous antibiotic-resistant infections were associated with risk for postoperative antibiotic-resistant infections (OR 1.81; 95% CI 1.16 to 2.83). Use of SAP was not associated with risk for postoperative antibiotic-resistant infections in a large cohort of patients with postoperative infections. This provides important reassurance regarding use of surgical antibiotic prophylaxis. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Robert, A; Nguyen, Y; Bajolet, O; Vuillemin, B; Defoin, B; Vernet-Garnier, V; Drame, M; Bani-Sadr, F
We aimed to evaluate factors associated with knowledge of antibiotics and drug resistance. A questionnaire was handed out by 14 family physicians to their patients between December 20, 2014 and April 20, 2015 in Rethel (North-East of France). We conducted a cross-sectional study using a logistical regression model to assess factors associated with antibiotic knowledge. Three criteria were used to assess that knowledge. Overall, 293 questionnaires were analysed; 48% of patients had received antibiotics in the previous 12 months. Only 44% and 26% gave a correct answer for the statements "Antibiotics are effective against bacteria and ineffective against viruses" and "Antibiotic resistance decreases if the antibiotic use decreases", respectively. Characteristics such as female sex, age>30 years, high level of education, high professional categories, and having received antibiotic information by the media were associated with high level of knowledge about antibiotics and/or antibiotic resistance. In contrast, having received antibiotic information from family physicians was not associated with good knowledge. Although media awareness campaigns had an independent impact on a higher public knowledge of antibiotics, the overall public knowledge remains low. It would be necessary to strengthen antibiotic campaigns with clearer information on the relation between the excessive use of antibiotics and the increased risk of antibiotic resistance. Family physicians should be more involved to improve antibiotic knowledge among target groups such as men, young patients, and people from a poor social and cultural background. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Zheng, Qingfei; Fang, Hui; Liu, Wen
Thiopeptide antibiotics are a class of typical ribosomally synthesized and post-translationally modified peptides (RiPPs) with complex chemical structures that are difficult to construct via chemical synthesis. To date, more than 100 thiopeptides have been discovered, and most of these compounds exhibit remarkable biological activities, such as antibacterial, antitumor and immunosuppressive activities. Therefore, studies of the biosynthesis of thiopeptides can contribute to the development of new drug leads and facilitate the understanding of the complex post-translational modifications (PTMs) of peptides and/or proteins. Since the biosynthetic gene clusters of thiopeptides were first discovered in 2009, several research studies regarding the biochemistry and enzymology of thiopeptide biosyntheses have been reported, indicating that their characteristic framework is constructed via a cascade of common PTMs and that additional specific PTMs diversify the molecules. In this review, we primarily summarize recent advances in understanding the biosynthesis of thiopeptide antibiotics and propose some potential applications based on our insights into the biosynthetic logic and machinery.
Neut, C; Mahieux, S; Dubreuil, L J
The main goal of this study was to determine the in vitro susceptibility of strains collected from marketed probiotics to antibiotics used to treat community-acquired infections. The minimum inhibitory concentrations (MICs) of 16 antibiotics were determined using a gradient strip (E test) or the agar dilution method for fidaxomicin. The probiotics demonstrated various antibiotic patterns. Bacterial probiotics are generally susceptible to most prescribed antibiotics orally administered, whereas yeast probiotics, such as Saccharomyces boulardii, are resistant. Special attention must be paid to co-prescriptions of antibiotics and probiotics to ensure that the probiotic strain is not susceptible. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Wang, G; Zhang, J; Mizuno, T; Zhuang, C; Ito, H; Mayuzumi, H; Okamoto, H; Li, J
A systematic method of extraction, fractionation, and purification of polysaccharides from Songshan Lingzhi (Ganoderma tsugae) with antitumor activity was established. Seven glycans with strong antitumor activities were obtained from 14 water-soluble, and 15 water-insoluble fractions: FIo-a, FA-1, FII-1, FIII-2, and FIII-2-a, -b, and -c. FIo-a and FA-1 were protein-containing glucogalactans associated with mannose and fucose. FII-1 was a (1-->3)-beta-D-glucan having a lower protein content. The water-insoluble fractions FIII-2-a, -b, and -c were extracted with alkali, and were found to be protein-containing (1-->3)-beta-D-glucans showing the strongest activity. Chemical properties and structure of each antitumor polysaccharide were compared with three fungi of the Ganoderma family, Kofukitake (G. applanatum), Mannentake (G. lucidum), and Songshan Lingzhi (G. tsugae).
Wu, Yue; Hu, Mingyang; Yang, Li; Li, Xiang; Bian, Jinlei; Jiang, Fen; Sun, Haopeng; You, Qidong; Zhang, Xiaojin
DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Wang, Shengzheng; Fang, Kun; Dong, Guoqiang; Chen, Shuqiang; Liu, Na; Miao, Zhenyuan; Yao, Jianzhong; Li, Jian; Zhang, Wannian; Sheng, Chunquan
A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of natural product-inspired scaffold diversity is an effective but challenging strategy to investigate the broader chemical space and identify promising drug leads. Extending our efforts to the natural product evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds and their derivatives were designed and synthesized. Most of them showed good to excellent antitumor activity against various human cancer cell lines. In particular, 3-chloro-10-hydroxyl thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery.
Elena Nicole Bodnar; Mikola Petrovich Dikiy; Elena Pavlivna Medvedeva
Incorporation of a radioisotope of platinum prepared with sufficiently high specific activity into the cisplatin molecule may significantly enhance the antitumor effect and decrease the therapeutically effective dosage of cisplatin chemotherapy. The objectives of our research were to develop a method of preparation of 195m Pt with high specific activity and then implement the synthesis of 195m Pt-cisplatin for in vitro and animal studies of its antitumor effect in comparison with non-radioactive cisplatin. Investigation of cisplatin and 195m Pt-cisplatin on Ehrlich solid carcinoma demonstrated tumor growth inhibition of 35 and 65 %, respectively, indicating 195m Pt-cisplatin is more effective than non-radioactive cisplatin in antitumor activity. (author)
Full Text Available Aromatic and medicinal plants have been traditionally used since antiquity to fight against illnesses. Recently, several researches have focused on the pharmacological properties and various bioactivities of natural products are extracted from medicinal plants, including the properties of antibacterial, antitumor and antioxidant activities. The products of medicinal plants are the secondary metabolites belonging to different compound classes such as essential oils, polyphenols, flavonoids and other phytochemical classes. In Morocco, medicinal plants are the major source of bioactive compounds and the majority of them are used in phytotherapy. The biological potential of various Moroccan medicinal plants attracts a lot of interest in the literature. They include antibacterial, antioxidant and antitumor investigations. In this context, this work aims at discussing antibacterial, antitumor and antioxidant properties of Moroccan medicinal plants.
Shi, Guilan; Zhou, Chunxia; Wang, Dongmei; Ma, Wenbo; Liu, Binlei; Zhang, Shuren
The present study investigated the antitumor effects by adoptive transfer of tumor antigen primed, inactivated MHC-haploidentical lymphocytes in TC-1 lung cancer mouse model. Our studies revealed that the inactivated MHC-haploidentical effecter cells display the antitumor activity in vitro and target the tumor in vivo. After adoptive transferring these effecter cells, the Th1 cytokines such as IL-2 and IFN-γ are elevated in the serum; the recipient tumor-specific cytotoxic T-cells and natural killer cells are activated; tumor specific memory T cells are induced; tumor growth is inhibited and mouse survival is prolonged. The results indicate that MHC-haploidentical lymphocytes provide both effecter cells which can target the tumor cells through the identical MHC molecules and an adjuvant effects through the unmatched allogeneic MHC molecules which induces endogenous innate and adaptive antitumor immune responses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Overgaard, Nana Haahr
The immune system plays a crucial role in cancer development and progression. Cancer immunoediting encompasses three phases: elimination, equilibrium, and escape; together, describing the complex interplay between tumor and immune cells. Specifically, the immune system both protects against cancer...... of autologous tumor cells, underlining the capacity of the Oncopig immune system to mount a cytotoxic anti-tumor response. Using the results from RNA-seq analysis, we propose a potential mechanism for in vivo inhibition of anti-tumor cytotoxicity based on elevated expression of the immunosuppressive genes IDO1...... support that the Oncopig provides a crucial platform for studying anti-tumor immune responses in a large in vivo system, although the model currently only allows preclinical testing of therapeutics against the early stages of cancer....
Ghada S. Hassan
Full Text Available New series of 1,2,4-triazolopyrimidine and 1,2,4-triazoloquinazoline derivatives were designed, synthesized, and evaluated for their antitumor activity. Compounds 6, 11, 26, 29, 41, 44, 48, 49 and 58 were tested as antitumor agents by the use of DNA-binding assay on TLC-plates, colorimetric assay for the degree of DNA-binding (Methyl green-DNA displacement assay, evaluation of antineoplastic activity against Ehrlich Ascites Carcinoma in mice, and finally modulation of apoptosis. 5-Flurouracil, vitamin C and ethidium bromide were used as positive controls in these techniques. Compound 26 proved to be the most active member of these series as antitumor agent with IC50 value of 47 ± 1. Several characteristic features were observed to be essential for activity such as the morpholine group and the phenylazo group, in addition the electron-withdrawing groups favor the activity than the electron-donating ones.
Colzani, Barbara; Pandolfi, Laura; Hoti, Ada; Iovene, Pietro Alessandro; Natalello, Antonino; Avvakumova, Svetlana; Colombo, Miriam; Prosperi, Davide
to allow for the simultaneous incorporation of TZ and conventional chemotherapeutics, resulting in a potent antitumor nanodrug well suited for in situ combination and neoadjuvant therapy.
Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.
Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp
Fujii, Shin-Ichiro; Shimizu, Kanako; Okamoto, Yoshitaka; Kunii, Naoki; Nakayama, Toshinori; Motohashi, Shinichiro; Taniguchi, Masaru
Human natural killer T (NKT) cells are characterized by their expression of an invariant T cell antigen receptor α chain variable region encoded by a Vα24Jα18 rearrangement. These NKT cells recognize α-galactosylceramide (α-GalCer) in conjunction with the MHC class I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-γ, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of α-GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN-γ production had significantly prolonged median survival times of 29.3 months with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 weeks after the combination therapy of α-GalCer-DCs and activated NKT cells. We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and α-GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even 1 year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS) cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN-γ in vitro and in vivo upon
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.
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.
Antibiotics are powerful therapeutic agents that are produced by diverse living organisms. Over the last several decades, natural bioactive products particularly antibiotics have continued to play a significant role in drug discovery and has expanded the process for developing drugs with high degree of therapeutic index and ...
Antibiotics represent a first line of defense of diverse microorganisms, which produce and use antibiotics to counteract natural enemies or competitors for nutritional resources in their nearby environment. For antimicrobial activity, nature has invented a great variety of mechanisms of antibiotic action that involve the perturbation of essential bacterial structures or biosynthesis pathways of macromolecules such as the bacterial cell wall, DNA, RNA, or proteins, thereby threatening the specific microbial lifestyle and eventually even survival. However, along with highly inventive modes of antibiotic action, nature also developed a comparable set of resistance mechanisms that help the bacteria to circumvent antibiotic action. Microorganisms have evolved specific adaptive responses that allow appropriately reacting to the presence of antimicrobial agents, ensuring survival during antimicrobial stress. In times of rapid development and spread of antibiotic (multi-)resistance, we need to explore new, resistance-breaking strategies to counteract bacterial infections. This chapter intends to give an overview of common antibiotics and their target pathways. It will also discuss recent advances in finding new antibiotics with novel modes of action, illustrating that nature's repertoire of innovative new antimicrobial agents has not been fully exploited yet, and we still might find new drugs that help to evade established antimicrobial resistance strategies.
The antibiotic resistance problem is the mobilization of genes that confer resistance to medically important antibiotics into human pathogens. The acquisition of such resistance genes by pathogens prevents disease treatment, increases health care costs, and increases morbidity and mortality. As ant...
Objectives. To determine the incidence of infection in snakebite patients, the bacterial species involved, and the indication for antibiotics. Method. A prospective trial was undertaken at Eshowe. Hospital, KwaZulu-Natal, involving 363 snakebite patients. (records available for 310 patients). It was protocol not to give antibiotics ...
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
Wentzel, M.J.; 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
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.
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.
Oct 3, 2017 ... In the last decade the detection of the resistance of bacteria to antibiotics treatment, developed by different kind of bacteria, is becoming a huge problem. We hereby present a different approach to the current problem of detection of bacteria resistance to antibiotics. Our aims were to use the atomic force ...
Harbarth, S.; Theuretzbacher, U.; Hackett, J.; Hulscher, M.; et al.,
The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is
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
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
de Lastours, V
While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve therapeutic success and to limit the risks of the emergence of resistance. The optimization of antibiotic use and dosages must have a threefold objective: guarantee antibacterial efficacy, limit toxicities and limit emergence of resistant strains. However, with the increase in the number of multipathological patients, particularly those with renal or hepatic impairment, the increase in the number of patients with extreme weights and the use of antibiotics with narrower therapeutic margins, the adaptation of antibiotic dosages is becoming increasingly important. By reminding some principles of pharmacokinetics and pharmacodynamics of antibiotics (PK/PD), the necessary objectives for clinical effectiveness of most antibiotic classes are reviewed and several examples of situations where dosage adjustments are necessary will be given. In particular, adjustment of antibiotic dosages in obese patients will be discussed. Adaptation is not limited to the adaptation of the total daily dose. The PK/PD parameters also tell us that the mode of administration (intermittent versus continuous, number of injections per day, etc.) is also an essential point to consider. By taking examples concerning some molecules, infections and difficult clinical situations, we review situations in which dosage adjustments appear necessary. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Sep 28, 2011 ... Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. ... biofilm formation abilities of antibiotic-sensitive Staphylococcus aureus KACC 13236 (SAS), multiple ... useful information for the comparison of antibiotic resistance patterns and biofilm formation abilities.
The Salmonella isolates tested displayed multiple antibiotic resistance to a number of antibiotics used to treat both humans and animals. No resistance was seen to disinfectants used at the manufacturer\\'s recommended rate of dilution. The bacteria were resistant, though, at lower dilutions, highlighting the necessity of ...
Methicillin resistant Staphylococcus aureus (MRSA) is a multidrug resistant bacterium that threatens the continued effectiveness of antibiotics worldwide. The objective of this study was to investigate the prevalence of MRSA and its antibiotic susceptibility pattern in patients with burns and bedsore. This was a cross- sectional ...
Pikkemaat, M.G.; Yassin, H.; Fels-Klerkx, H.J.; Berendsen, B.J.A.
Antibiotic usage has benefited the animal industry and helped providing affordable animal proteins to the growing human population. However, since extensive use of antibiotics results in the inhibition of susceptible organisms while selecting for the resistant ones, agricultural use is contributing
The objective of this study was to design nano-antibiotic to enhance their release from biomaterial agents. Cefotaxime was used as a model antibiotic substance in this carrier system. These nanoparticles were preformulated using different concentrations of polycaprolactone (PCL) and poly (vinyl alcohol) as coating material ...
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. Project HOPE—The People-to-People Health Foundation, Inc.
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)
Ahmed, M.; Asghar, I.; Mansoor, N.
To find out the incidence of surgical site infection in clean general surgery cases operated without prophylactic antibiotics. One hundred and twenty-four clean surgical cases operated without antibiotic prophylaxis between July 2003 and December 2004, were studied and these were compared with similar number of cases who received antibiotics. The data was collected and analyzed using software SPSS (version 10.0). Chi-square and student-t test were used to analyze the association between antibiotics and wound infection. The most frequent operation was repair of various hernias, 69.3% in group A and 75% in group B. More operations were carried out between 21-30 years, 38.7% in group A and 41.9% in group B. Surgical site infection occurred in one patient (0.8%) in each group. Chi-square test (0.636) applied to group A and B showed no association of infection and administration/ no administration of antibiotics (p > 0.25). The t-test applied on group A and B (t=0) also showed no significant difference between administration of antibiotics/ no-antibiotics and infection (p > 0.25). The use of prophylactic antibiotic in clean, non implant and elective cases is unnecessary. (author)
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...
Liu, Weiming; Ni, Ming; Zhang, Yuewei; Groen, Rob J. M.
The effectiveness of antibiotic prophylaxis (AP) in craniotomies has been clarified through the accumulation of evidence and increased antibiotic knowledge. This paper focuses on the use of AP in craniotomies during different historical periods and collects highly relevant evidence on this issue.
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.
Bukharin, O V; Perunova, N B; Fadeev, S B; Timokhina, T Kh; Iavnova, S V
To study of circadian dynamics of antibiotic susceptibility and resistance of Gram-positive and Gram-negative microorganisms. Circadian dynamics of antibiotic susceptibility was studied on clinical strains of enterobacteria, non-fermenting Gram-negative bacteria, and staphylococci which were isolated and identified by common methods. During a day, with 3-hours intervals, studied strains were tested on susceptibility to ampicillin, oxacillin, ceftriaxone, meropenem, gentamycin, and ciprofloxacin using method of serial dilutions in agar. Circadian biorhythms of resistance to antibiotics in studied microorganisms were revealed. Along with common patterns, differences in temporal changes of microrganisms' susceptibility to antibacterial drugs were noted. Chronobiologic approach allowed to reveal significant amplitude of changes of minimal inhibitoryconcentration (MIC) of antibiotics versus resistant Gram-positive cocci reflecting presence of susceptibility periods, whereas in susceptible Gram-negative bacteria peaks of resistance were observed. Circadian dynamics of MIC of majority of antibiotics versus resistant Gram-negative bacteria and susceptible Gram-positive cocci was characterized by lower amplitude of changes without shifts from antibiotic resistance to susceptibility and vice versa. Obtained data open perspective of using biorhythmological approach in study of susceptibility of microorganisms to antibiotics during the elucidation of mechanisms of pathogens adaptation to environmental conditions and creation of new strategies of control for antibiotic resistance strains.
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.
In particular, we studied Klebsiella pneumoniae bacteria provided by the Lavagna Hospital ASL4Liguria (Italy), where there are cases linked with antibiotics resistance of the Klebsiella pneumoniae. By comparing AFMimages of bacteria strains treated with different antibiotics is possible to identify unambiguously the ...
In the last decade the detection of the resistance of bacteria to antibiotics treatment, developed by different kind of bacteria,is becoming a huge problem. We hereby present a different approach to the current problem of detection of bacteriaresistance to antibiotics. Our aims were to use the atomic force microscopy (AFM) to ...
Roque, Fátima; Soares, Sara; Breitenfeld, Luiza; Figueiras, Adolfo; Herdeiro, Maria Teresa
Excessive and inappropriate use of antibiotics, are attributed to inadequate prescription and self-medication with antibiotics obtained from leftovers from previous courses or self-medication with antibiotics dispensed in pharmacies without prescription.
Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.
Stigter, M; Bezemer, J; de Groot, 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 within this study: cephalothin, carbenicillin, amoxicillin, cefamandol, tobramycin, gentamicin and vancomycin. Increased concentrations of antibiotics in the coating solution led to a higher quantity of antibiotic incorporated into the CHA coating. Some antibiotics were better incorporated than others depending on their chemical structure. Antibiotics, containing carboxylic groups such as cephalothin, carbenicillin and cefamandol, were better incorporated than antibiotics lacking these groups. A bacterial inhibition test on Staphylococcus aureus bacteria showed inhibition of growth for all antibiotics that were released from the CHA coating. A release test was conducted in phosphate buffer saline PBS at pH 7.4 and 37 degrees C and showed that antibiotics containing carboxylic groups like cephalothin were slower released from the CHA coating than others. These results suggest that certain antibiotics are able to bind/chelate with calcium, resulting in a better incorporation into the CHA coating and a slower release. Antibiotics incorporated in CHA coatings on titanium implants might be used to prevent post-surgical infections and to promote bone-bonding of orthopedic devices.
Price, Lance B.; Newland, Jason; Bole, Aparna
edical and public health organizations around the world agree that more prudent use of antibiotics in human medicine and in livestock production is paramount to slow the spread of antibiotic resistance. Of particular concern is the widespread use of antibiotics important to human medicine in food...... animals. In the U.S., such use accounts for 70% of all sales of medically important antibiotics. It is against this backdrop that 12 antibiotic resistance experts from the fields of infectious disease medicine, veterinary medicine, microbiology, epidemiology and public health joined to craft a policy...... roadmap to help move the U.S. forward in addressing the contribution of livestock antibiotic use to the growing global threat of antibiotic resistance. The policy roadmap consists of 11 core policy recommendations that are aimed at a broad set of stakeholders: federal, state and local policymakers, food...
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.
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.
Bohn, Pernille; Bak, Søren A; Björklund, Erland
Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C...... for maximum 34 days. Using LC-MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.......6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis...
We face a global antibiotics resistance crisis. Antibiotic drugs are rapidly losing their effectiveness, potentially propelling us toward a post-antibiotic world. The largest use of antibiotics in the world is in food-producing animals. Food producers administer these drugs in routine, low doses—the types of doses that are incidentally the most conducive to breeding antibiotic resistance. In general, individual countries have been too slow to act in regulating misuse and overuse of antibiotics in foodproducing animals. This problem will only worsen with the significant projected growth in meat consumption and production expected in emerging economies in the near future. Although individual countries regulating antibiotics can have important effects, one country alone cannot insulate itself entirely from the effects of antibiotic resistance, nor can one country solve the crisis for itself or for the world. The global nature of the food system and the urgency of the problem require immediate global solutions. Adapting a democratic experimentalist approach at the international level can help achieve this goal. Using an international democratic experimentalist framework in conjunction with the World Organization for Animal Health (OIE) would provide for increased systematized data collection and lead to heightened, scientifically informed OIE standards, enforceable by the World Trade Organization (WTO), which could have a significant impact on the reduction of subtherapeutic use of antibiotics internationally. International democratic experimentalism addresses the global intricacy, time sensitivity, context- and culture-specificity, and knowledgeintensiveness of this problem. By encouraging more countries to experiment to solve this problem, the democratic experimentalist model would help develop a larger database of solutions to enable more meaningful cross-country comparisons across a wider range of contexts. This approach maintains democratic governance and
Dantas, Gautam; Sommer, Morten Otto Alexander
This chapter contains sections titled: Introduction Environmental Origins of Resistance: The Producer Hypothesis Resistome of other Soil Bacteria: Response to the Producers? Early Reports of Antibiotic Catabolism by Soil Bacteria The Antibiotic Subsistome: Who and how much? Antibiotic Subsistence...... as a Scavenger Phenotype Ecological Consequences of the Antibiotic Subsistome Investigating Connections Between Subsistomes and Resistomes Metagenomic Functional Selections for Discovering Genes Enabling Antibiotic Subsistence and Resistance Antibiotic Subsistence by Pathogenic Bacteria Concluding Remarks...
Laura Masuelli; Monica Benvenuto; Rosanna Mattera; Enrica Di Stefano; Erika Zago; Gloria Taffera; Ilaria Tresoldi; Maria Gabriella Giganti; Giovanni Vanni Frajese; Ginevra Berardi; Andrea Modesti; Andrea Modesti; Roberto Bei; Roberto Bei
Malignant mesothelioma (MM) is a tumor arising from mesothelium. MM patients’ survival is poor. The polyphenol 4′,5,7,-trihydroxyflavone Apigenin (API) is a “multifunctional drug”. Several studies have demonstrated API anti-tumoral effects. However, little is known on the in vitro and in vivo anti-tumoral effects of API in MM. Thus, we analyzed the in vitro effects of API on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, and autophagy of human and mouse...
Eyong, Kenneth O; Kumar, Ponminor S; Kuete, Victor; Folefoc, Gabriel N; Nkengfack, Ephriam A; Baskaran, Sundarababu
Ozonolysis of lapachol (1), resulting in an unusual formation of a potent antitumor agent 2-acetylfuranonaphthoquinone (3) along with the expected aldehyde 6, is described. The reaction of lapachol (1) with CAN in dry acetonitrile leading to biologically active furanonaphthoquinones is also reported. The antitumoral activity of the tested compounds on human DU-145 prostate carcinoma cells was evaluated following XTT assay. The results revealed that 2-(1-methylethenyl)-2,3-dihydronaphtho[2,3-b]furan-4,9-dione (5), beta-lapachone (10) and dehydro-beta-lapachone diacetate (11) showed 100% inhibition at 25 microg/ml. All the tested samples showed dose-dependent activity.
Full Text Available Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by 1H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460, human colon adenocarcinoma (SW480, human breast cancer cell (MDA-MB-468 and SKRB-3, human melanoma cell (A375 and human pancreatic cancer (BxPC-3 . Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.
El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar
Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....
Buege, Michael J; Brown, Jack E; Aitken, Samuel L
The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance. Phase III clinical trials of solithromycin demonstrated noninferiority of both oral and i.v.-to-oral regimens of 5-7 days' duration compared with moxifloxacin for patients with moderately severe CABP. Nearly one third of patients receiving i.v. solithromycin experienced infusion-site reactions. Although no liver-related adverse events were reported in patients receiving oral solithromycin, more patients receiving i.v.-to-oral solithromycin experienced asymptomatic, transient transaminitis, with alanine transaminase levels of >3 to >5 times the upper limit, compared with those treated with moxifloxacin. These results led the Food and Drug Administration to conclude that the solithromycin new drug application was not approvable as filed, adding that the risk of hepatotoxicity had not yet been adequately characterized. The agency further recommended a comparative study of patients with CABP to include approximately 9,000 patients exposed to solithromycin in order to exclude drug-induced liver injury events occurring at a rate of 1 in 3,000 with 95% probability. Solithromycin is a novel ketolide antibiotic with activity against a broad spectrum of intracellular organisms, including those displaying macrolide resistance. While demonstrating noninferiority to a current first-line agent in the treatment of CABP, concerns for drug-induced liver injury and infusion-site reactions have placed its regulatory future in doubt. Copyright © 2017 by the American Society of
El-Halfawy, Omar M; Klett, Javier; Ingram, Rebecca J; Loutet, Slade A; Murphy, Michael E P; Martín-Santamaría, Sonsoles; Valvano, Miguel A
The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa , Mycobacterium tuberculosis , and methicillin-resistant Staphylococcus aureus Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins. IMPORTANCE Current research on antibiotic action and resistance focuses on targeting essential functions within bacterial cells. We discovered a previously unrecognized mode of general bacterial antibiotic resistance operating in the extracellular space, which depends on bacterial protein molecules called lipocalins. These molecules are highly conserved in most bacteria and have the ability to capture different classes of antibiotics outside bacterial cells. We also discovered that liposoluble vitamins, such as vitamin E, overcome in vitro and in vivo antibiotic resistance mediated by bacterial lipocalins, providing an unexpected new alternative to combat resistance by using this vitamin or its derivatives as antibiotic adjuvants. Copyright © 2017 El-Halfawy et al.
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.
Multhoff, G. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik fuer Strahlentherapie und Radiologische Onkologie, Experimentelle Radioonkologie; Helmholtz-Zentrum Muenchen (HMGU) (Germany). Klinische Kooperationsgruppe: ' Angeborene Immunantwort in der Tumorbiologie' ; Gaipl, U.S. [Universitaetsklinikum Erlangen (Germany). Strahlenklinik/Radioonkologie, Strahlen-Immunbiologie; Niedermann, G. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde, Sektion fuer Klinische und Experimentelle Strahlenbiologie
Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.
Full Text Available Abstract Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in
van de Garde, Ewoudt M. W.; Natsch, Stephanie; Prins, Jan M.; van der Linden, Paul D.
Objective: Most pneumonia treatment guidelines recommend that prior outpatient antibiotic treatment should be considered when planning inpatient antibiotic regimen. Our purpose was to study in patients admitted for community-acquired pneumonia the mode of continuing antibiotic treatment at the
Van De Garde, Ewoudt M W|info:eu-repo/dai/nl/304841528; Natsch, Stephanie; Prins, Jan M.; Van Der Linden, Paul D.
Objective: Most pneumonia treatment guidelines recommend that prior outpatient antibiotic treatment should be considered when planning inpatient antibiotic regimen. Our purpose was to study in patients admitted for community-acquired pneumonia the mode of continuing antibiotic treatment at the
Garde, E.M. van de; Natsch, S.S.; Prins, J.M.; Linden, P.D. van der
OBJECTIVE: Most pneumonia treatment guidelines recommend that prior outpatient antibiotic treatment should be considered when planning inpatient antibiotic regimen. Our purpose was to study in patients admitted for community-acquired pneumonia the mode of continuing antibiotic treatment at the
There is widespread interest in monitoring the development of antibiotic resistant bacteria and antibiotic resistance genes in agriculturally impacted environments, however little is known about the relationships between bacterial community structure, and antibiotic resistance gene profiles. Cattl...
Watkins, Richard R; Bonomo, Robert A
The rapid and ongoing spread of antibiotic resistance poses a serious threat to global public health. The indiscriminant use of antibiotics in agriculture and human medicine along with increasingly connected societies has fueled the distribution of antibiotic-resistant bacteria. These factors together have led to rising numbers of infections caused by multidrug-resistant and pan-resistant bacteria, with increases in morbidity and mortality. This article summarizes the trends in antibiotic resistance, discusses the impact of antibiotic resistance on society, and reviews the use of antibiotics in agriculture. Feasible ways to tackle antibiotic resistance to avert a post-antibiotic era are suggested. Copyright © 2016 Elsevier Inc. All rights reserved.
Gbaguidi-Haore, Houssein; Dumartin, Catherine; L'Hériteau, François; Péfau, Muriel; Hocquet, Didier; Rogues, Anne-Marie; Bertrand, Xavier
To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.
Full Text Available A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela. The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1, mahanimbicine (2 and mahanimbine (3. The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS. These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU, Psedomonas aeruginosa (ATCC 25619, Klebsiella pneumonia (SR1-TU, Escherchia coli (NI23 JTU and Streptococcus pneumoniae (SR16677-PRSP with significant minimum inhibition concentration (MIC values (25.0–175.0 mg/mL and minimum bacteriacidal concentrations (MBC (100.0–500.0 mg/mL. The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3 and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL. The findings from this investigation are the first report of carbazole alkaloids’ potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.
Queiroz, Rodrigo Guimaraes
Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)
Kimman, T.G.; Smits, M.A.; Kemp, B.; Wever, P.; Verheijden, J.
Resistance of bacteria to antibiotics in animal husbandry is increasing and a point of growing concern. The large use of antibiotics in agriculture undoubtedly leads to the development of antibiotic resistance. This has resulted in a growing public concern on the rise of antibiotic resistance, and in particular on the transmission of resistant bacteria and resistance markers from animals to humans. Large antibiotic use in animal husbandry and antibiotic resistance threatens the health and wel...
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
Parkes, Alastair L; Yule, Ian A
There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.
Lucas, M; Germain, J-M; Rémy, E; Lottin, M; Etienne, M; Czernichow, P; Merle, V
French national guidelines state that antibiotic therapies should be reassessed between 48 and 72hours after treatment initiation and that reassessment of antibiotic therapy (RA) must be recorded in patients' files. To determine whether RA is performed and recorded in patients' files in hospitals in a region of France. Setting: hospitals participating in the National nosocomial infection point- prevalence survey (NPS) in Upper-Normandy, France. Patients included those receiving antibiotic therapy (excluding antibiotic prophylaxis) on NPS day, started in the hospital in which the survey was conducted and ongoing for more than 72hours. Data collected included characteristics of participating hospitals and, for each included patient, characteristics of ward, infection and antibiotic therapy, and mention in the patients' files of explicit or implicit RA. The rate of explicit and implicit RA was calculated and factors associated with explicit or implicit RA were evaluated using a univariate analysis. Thirty-three hospitals representing 87% of hospital beds region-wide were included in the study. In addition, 933 prescriptions were assessed for 724 infections in 676 patients. The overall rate of RA was 67.6% (49.3% of explicit RA and 18.3% of implicit RA). The rate of RA differed significantly according to infection and antibiotic class but not according to hospital or ward characteristics. Our study provides new and reassuring results regarding reassessment of antibiotic therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Andrade, Melisa J; Jayaprakash, Chinchu; Bhat, Smitha; Evangelatos, Nikolaos; Brand, Angela; Satyamoorthy, Kapaettu
Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity. Apart from the involvement of biosocial causes influencing diet, physical activity, and antibiotic use, pathogenesis of obesity is linked to interconnected functional alterations in cells, tissues and organs due to biochemical, epigenetic and genetic factors. Mitochondrial dysfunction is one such factor, which is becoming the primary focus of various aspects of research on multifactorial complex diseases and is providing new perspectives on etiology, biomarker-based diagnosis, and drug sensitivity. Through this review, we have made an attempt to present the interplay between use of antibiotics, obesity, and associated mitochondrial dysfunction. This may provide insights into the molecular basis, genetic predisposition and environmental triggers, which in turn may have potential clinical applications in the management of antibiotic use. © 2017 S. Karger AG, Basel.
Liu, Gang; Chandra, Govind; Niu, Guoqing
SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619
Pradipta, Ivan Surya; Sodik, Dian Chairunnisa; Lestari, Keri; Parwati, Ida; Halimah, Eli; Diantini, Ajeng; Abdulah, Rizky
Background: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. Aims: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. Materials and Methods: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. Results: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. Conclusions: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients. PMID:23923107
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.
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. Copyright © 2016 Elsevier Ltd. All rights reserved.
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. Copyright © 2016 John Wiley & Sons, Ltd.
Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID:26356096
van Daalen, Frederike Vera; Lagerburg, Anouk; de Kort, Jaclyn; Sànchez Rivas, Elena; Geerlings, Suzanne Eugenie
No interventions have yet been implemented to improve antibiotic use on Aruba. In the Netherlands, the introduction of an antibiotic checklist resulted in more appropriate antibiotic use in nine hospitals. The aim of this study was to introduce the antibiotic checklist on Aruba, test its effectiveness, and evaluate the possibility of implementing this checklist outside the Netherlands. The antibiotic checklist includes seven quality indicators (QIs) that define appropriate antibiotic use. It applies to adult patients with a suspected bacterial infection, treated with intravenous antibiotics. The primary endpoint was the QI sum score, calculated by the patient's sum of performed checklist-items divided by the total number of QIs that applied to that specific patient. Outcomes before and after the introduction of the checklist were compared. The percentage of patients with a QI sum score ≥50% increased significantly during the intervention (n=173) compared to baseline (n=150) (odds ratio 3.67, pchecklist was used in 63.3% of the eligible patients. The introduction of the antibiotic checklist increased appropriate antibiotic use on Aruba. Additional initiatives are necessary for further improvement per QI. These results suggest that the antibiotic checklist could be used internationally. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Dalton Espíndola Volpato
Full Text Available The inappropriate use of antibiotics for the treatment of infections is a worldwide problem that has implications for the cost of treatment and the development of resistant strains of bacteria. The use of antibiotics should follow specific criteria; they are on top of the list of self-medication drugs in countries that do not control their commercialization. OBJECTIVES: To determine the percentage of pharmacies that attend the public and sell antibiotics without medical prescription in a medium-sized city in Brazil, and analyze the variables involved in this procedure. MATERIALS AND METHODS: 107 of the 136 pharmacies registered in our city were evaluated. These pharmacies were visited by actresses who simulated having a sister with symptoms of a non-complicated rhino-sinusitis, so that they could obtain antibiotics without a medical prescription. Each pharmacy was visited only once; the only variable in the simulated clinical setting was the report of fever temperature, which was randomly assigned between 38.5 and 40 degrees Celsius. RESULTS: Antibiotics were offered in 58% of the pharmacies, and this offer was increased to 74% after the actresses insisted on having them. In 65.4% of the pharmacies, the actresses were attended by a pharmacist, and 84.2% of them said they would sell antibiotics. When the request for antibiotics was denied (26%, only 7.5% was due to absence of prescription. The most frequent reason for refusal to sell antibiotics, was because the attendant deemed it unnecessary (46.6% CONCLUSION: Antibiotics can be easily bought in the great majority of the pharmacies in our town without a medical prescription and a clear indication. Fever temperature did not modify the attendant's indication of the drug.
Pohl, Nicola L.
Polyketide synthases (PKSs), a class of enzymes found in soil bacteria that produce antibiotics such as erythromycin, string together acetate units using basic organic reactions. The manipulation of the sequence of these reactions at the genetic level has resulted in an alteration of the corresponding chemical structure of the antibiotic produced by the bacteria. This process, called combinatorial biosynthesis, allows the generation of many presently unknown complex structures that can be tested for antibacterial activity, thereby contributing to the race against antibiotic-resistant infectious bacteria.
De; Anil, A.C.
environment – a review – Part II. Chemosphere, 2009, 75, 435–441. 21. Martinez, J. L., Environmental pollution by antibiotics and by antibiotic resistance determinants. Environ. Pollut., 2009, 157, 2893–2902. 22. Gavalchin, J. and Katz, S. E... CURRENT SCIENCE, VOL. 102, NO. 11, 10 JUNE 2012 1552 *For correspondence. (e-mail: firstname.lastname@example.org) The effect of antibiotics on diatom communities Priya M. D’Costa and Arga Chandrashekar Anil* CSIR-National Institute of Oceanography, Dona Paula, Goa...
Methods for the reductive methylation of the amino groups of eight different antibiotics using 3 HCOH or H 14 COH are presented. The reductive labeling of an additional seven antibiotics by NaB 3 H 4 is also described. The specific activity of the methyl-labeled drugs was determined by a phosphocellulose paper binding assay. Two quantitative assays for these compounds based on the reactivity of the antibiotic amino groups with fluorescamine and of the aldehyde and ketone groups with 2,4-dinitrophenylhydrazine are also presented. Data on the cellular uptake and ribosome binding of these labeled compounds are also presented
Luara de Sousa Monteiro
Full Text Available Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.
Plšíková, J.; Janovec, L.; Koval, J.; Ungvarsky, J.; Mikeš, J.; Jendželovský, R.; Fedoročko, P.; Imrich, J.; Kristian, P.; Kašpárková, Jana; Brabec, Viktor; Kozurková, M.
Roč. 57, č. 2012 (2012), s. 283-295 ISSN 0223-5234 Institutional research plan: CEZ:AV0Z50040702 Keywords : acridine * DNA intercalator * antitumor agents Subject RIV: BO - Biophysics Impact factor: 3.499, year: 2012
Lü, Shuhe; Lin, Cong; Xu, Pingsheng
Three fractions (SM, SM-A, SM-B) were prepared from different polarity parts of Ipomoea batatas Lam. (cv.simon) leaves and the anti-tumor potency as well as the dose-response relations were evaluated. The anti-tumor activities of fraction SM, SM-A or SM-B were screened by MTS in human hepatic cancer Hep3B cells, lung cancer A549 cells or gastric carcinoma MGC803 cells, respectively. The three fractions all showed anti-tumor activities in three cancer cells with different sensitivity. Among them, SM-B was the most potent fraction with IC50 values at 15.17 mg/L, 72.64 mg/L or 165.47 mg/L in MGC803 cells, A549 cells or Hep3B cells, respectively (P<0.05). Th e extraction of Brazil sweet potato leaves displayed anti-tumor activity and SM-B was the most potent fraction.
Marcin P Komorowski
Full Text Available Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. The infected cultures were more sensitive to doxorubicin-mediated killing both in vitro and in tumor-challenged mice. Mechanistically, the combination treatment increased apoptosis and phagocytosis of tumor material by dendritic cells associated with induction of antitumor immunity. Targeting syngeneic tumors with this regimen increased intratumoral infiltration of antitumor CD8+ T cells. This was further enhanced by reducing the immunosuppressive network by the virally-delivered CXCR4 antagonist, which augmented antitumor immune responses and led to tumor-free survival. Our results define novel strategies for treatment of drug-resistant ovarian cancer that increase immunogenic cell death and reverse the immunosuppressive tumor microenvironment, culminating in antitumor immune responses that control metastatic tumor growth.
Peranzoni, Elisa; Rivas-Caicedo, Ana; Bougherara, Houcine; Salmon, Hélène; Donnadieu, Emmanuel
The migration of T cells and access to tumor antigens is of utmost importance for the induction of protective anti-tumor immunity. Once having entered a malignant site, T cells encounter a complex environment composed of non-tumor cells along with the extracellular matrix (ECM). It is now well accepted that a deregulated ECM favors tumor progression and metastasis. Recent progress in imaging technologies has also highlighted the impact of the matrix architecture found in solid tumor on immune cells and especially T cells. In this review, we argue that the ability of T cells to mount an antitumor response is dependent on the matrix structure, more precisely on the balance between pro-migratory reticular fiber networks and unfavorable migration zones composed of dense and aligned ECM structures. Thus, the matrix architecture, that has long been considered to merely provide the structural framework of connective tissues, can play a key role in facilitating or suppressing the antitumor immune surveillance. A new challenge in cancer therapy will be to develop approaches aimed at altering the architecture of the tumor stroma, rendering it more permissive to antitumor T cells.
Lipovová, P.; Podzimek, T.; Orctová, Lidmila; Matoušek, Jaroslav; Poučková, P.; Souček, J.; Matoušek, Josef
Roč. 55, - (2008), s. 158-164 ISSN 0028-2685 Institutional research plan: CEZ:AV0Z50510513; CEZ:AV0Z50450515 Keywords : pollen nuclease * Antitumor effect Subject RIV: FD - Oncology ; Hematology Impact factor: 1.179, year: 2008
Sep 20, 2010 ... especially on anti-tumor. The reports on the biological activities of triterpenoids ... Helium was used as a carrier gas at a flow rate of 1. mL/min. 1 µL EBS sample dissolved in dichloromethane was ... The Silica Gel Column Chromatography and Countercurrent Chro- matography preparation techniques were ...
Kašpárková, Jana; Brabec, Viktor
Roč. 153, DEC2015 (2015), s. 206-210 ISSN 0162-0134 R&D Projects: GA ČR(CZ) GA14-21053S; GA MŠk(CZ) LD14019 Institutional support: RVO:68081707 Keywords : Transplatinum * Antitumor * Cellular target Subject RIV: BO - Biophysics Impact factor: 3.205, year: 2015
Aug 15, 2011 ... The in vitro anti-tumor potential of the extract was evaluated using MTT (3-(4,5- dimethythiazol-2yl)2 ... were compared with mitogen stimulated T-lymphocyte cultures derived from peripheral blood of healthy volunteers. The MTT test ... showed significant activity against lung carcinoma in vivo. (Wassel et al.
In vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth. Ren Qiu-Rong, Li Jiao, Wang Ya-Nan, Gou Xun, Xin Wen-Yuan, Ma Dan-Wei, Xiong Xiu-Hong, Zhou Yu-Jun ...
Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin ...
Mut-Salud, Nuria; Álvarez, Pablo Juan; Garrido, Jose Manuel; Carrasco, Esther; Aránega, Antonia; Rodríguez-Serrano, Fernando
The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency. PMID:26682013
α-Momorcharin (α-MMC) is the ribosome inactivating protein (RIPs) found to possess antitumor activity. However, acute toxicity and short plasma ... milder immunological reaction in rabbits when α-MMC is conjugated with PEG (Bian et al., ... tunneled 1 to 2 cm to prevent leakage of cell inoculum. For each strain of mouse, 80 ...
Cappellacci, L; Franchetti, P; Vita, P; Petrelli, R; Grifantini, M
A heterodinucleotide comprising BVDU and Gemcitabine bound together by a 5',5'-pyrophospate bridge (BVDUp(2)dFdC) has been synthesized and evaluated as antitumor agent against AH13 rat sarcoma cells. BVDUp(2)dFdC showed a cytotoxicity similar to that of Gemcitabine.
Wu, Yuanhao; He, Guanping; Zhang, Yu; Liu, Yang; Li, Mei; Wang, Xiaolan; Li, Nan; Li, Kang; Zheng, Guan; Zheng, Yufeng; Yin, Qingshui
In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.
Background: The main aim of this study was to demonstrate the antitumor potential of cucurbitacin A on A-549 NSCLC (non-small cell lung cancer cells). The effects of Cucurbitacin A on apoptotic induction, cell physic, cell cycle failure and m-TOR/PI3K/Akt signalling pathway were also investigated in the present study.
Kawahara, Mamoru; Takaku, Hiroshi
Although tumor lysate contains all the potential helper and killer epitopes capable of stimulating T cells, it is difficult to use as a cancer vaccine because it suppresses dendritic cell (DC) function. We report that wild-type baculovirus possesses an adjuvant effect to improve the immunogenicity of tumor lysate. When mice were administered CT26 tumor cell lysate combined with baculovirus intradermally, antitumor immunity was induced and rejection of CT26 tumor growth was observed in 40% of the immunized mice. In contrast, such antitumor immunity was not elicited in mice inoculated with tumor cell lysate or baculovirus alone. In tumor-bearing mice, which had previously received the combined baculovirus and tumor lysate vaccine, the established tumors were completely eradicated by administering a booster dose of the combined vaccine. This antitumor effect was attributed to tumor-specific T cell immunity mediated primarily by CD8⁺ T cells. Baculovirus also strongly activated DCs loaded with tumor lysate. Increased interleukin (IL)-6 and IL-12p70 production were also observed in DCs co-cultured with tumor cell lysate and baculovirus. Our study demonstrates that combined baculovirus and tumor lysate vaccine can effectively stimulate DCs to induce acquired antitumor immunity.
Olivová, R.; Kašpárková, Jana; Vrána, Oldřich; Vojtíšková, Marie; Suchánková, T.; Nováková, Olga; He, W.; Guo, Z.; Brabec, Viktor
Roč. 8, č. 6 (2011), s. 2368-2378 ISSN 1543-8384 R&D Projects: GA MŠk(CZ) ME10066 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum * antitumor * DNA Subject RIV: BO - Biophysics Impact factor: 4.782, year: 2011
Itokawa, H; Totsuka, N; Morita, H; Takeya, K; Iitaka, Y; Schenkel, E P; Motidome, M
New antitumor clerodane diterpenes, named casearins A-F, have been isolated from the leaves of Casearia sylvestris Sw. (Flacourtiaceae). These structures have been completely elucidated by two dimensional nuclear magnetic resonance, circular dichroism spectroscopy, X-ray analysis, and chemical evidences.
Purpose: To investigate the anti-thrombosis and anti-tumor effect of the water extract of the caulis of Sargentodoxa cuneata (Oliv.) Rehd. et Wils. (WCSW) in rat and mouse models. Methods: WCSW extract was prepared and the main constituents were determined by high pressure liquid chromatography (HPLC). The acute ...
Bamboo shavings are a kind of Chinese traditional medicine, which have been certificated as a material of functional food by the Ministry of Health in China. The anti-tumor activities of a triterpenoid-rich extract of bamboo shavings (EBS) and its main component, friedelin were evaluated in the present study. It was proved ...
The total alkaloid extract from Prosopis juliflora DC. leaves was obtained using acid/base modified extraction method. The in vitro anti-tumor potential of the extract was evaluated using MTT (3-(4,5- dimethythiazol-2yl)2,5-diphenyl tetrazolium bromide) based cytotoxicity monitoring after 24, 48 and 72 h exposure of the ...
We studied the in vitro anti-tumor activity of Bidens Bipinnata L. extract. MTT assay was used to investigate the inhibitory effect of different concentrations of the extracts on human hepatocellular carcinoma (HepG2) cell lines and human cervical carcinoma (Hela) cell lines, and the IC50 values were calculated. The Bidens ...
Miyashita, Michiko; Sadzuka, Yasuyuki
As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents. In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined. In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown. In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group. The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na(+). This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration. It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na(+)-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX. Therefore, linalool as a food component is anticipated to be an effective DOX modulator. Copyright © 2012 Elsevier Ltd. All rights reserved.
Rastija, Vesna; Bajić, Miroslav; Stolić, Ivana; Krstulović, Luka; Jukić, Marijana; Glavaš-Obrovac, Ljubica
QSAR analysis was performed for the antitumor activity of 27 derivatives of 3,4-ethylenedioxythiophene against six carcinoma cell lines. The best models were obtained with surface area (SAG) in combination with lipohilicity (log P) as descriptors. Results have shown that molecules with smaller solvent accessible surface area and higher lipophilicy should have higher biological activity against carcinoma cell.
Gál, Miroslav; Híveš, J.; Laus, M.; Sparnacci, K.; Ravera, M.; Gabano, E.; Osella, D.
-, č. 22 (2011), s. 3289-3294 ISSN 1434-1948 R&D Projects: GA ČR GP203/09/P502 Institutional research plan: CEZ:AV0Z40400503 Keywords : platinum * Antitumor agents * nanoparticles Subject RIV: CG - Electrochemistry Impact factor: 3.049, year: 2011
Anti-tumor activity of tetrodotoxins extracted from the skin of the Masked Puffer fish (Arothron diadematus) from the Red Sea was evaluated using the Ehrlich ascite carcinoma tumor model in mice. Activity was assessed using a variety of cellular and liver biochemical parameters. Experimental mice were divided into 4 equal ...
Man, Shuli; Li, Yuanyuan; Fan, Wei; Gao, Wenyuan; Liu, Zhen; Li, Nan; Zhang, Yao; Liu, Changxiao
Rhizoma paridis saponins (RPS) played a good antitumor role in many clinical applications. However, low oral bioavailability limited its application. In this research, water extract of Curcuma (CW) significantly increased antitumor effect of Rhizoma paridis saponins (RPS). GC-MS was used to identify its polar composition. HPLC was applied for determination of the content of curcuminoids in CW. As a result, 47 analytes with 0.65% of curcuminoids were identified in CW. According to the in vivo anti-tumor data, the best proportion of curcuminoids in CW with RPS was 16:500 (w/w). Using this ratio, curcuminoids significantly increased absorption of RPS in the everted rat duodenum sac system. In addition, curcuminoids decreased the promotion of RPS on rhodamine 123 efflux. The effect of curcuminoids was similar to that of the P-gp inhibitor, cyclosporin A in combination with RPS. In conclusion, drug combination of water extract of Curcuma with RPS was a good method to increase the antitumor effect of RPS. This combination would be a potent anticancer agent used in the prospective application. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.
Chen, Degao; Xie, Jing; Fiskesund, Roland; Dong, Wenqian; Liang, Xiaoyu; Lv, Jiadi; Jin, Xun; Liu, Jinyan; Mo, Siqi; Zhang, Tianzhen; Cheng, Feiran; Zhou, Yabo; Zhang, Huafeng; Tang, Ke; Ma, Jingwei; Liu, Yuying; Huang, Bo
Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca 2+ release via the lysosomal Ca 2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca 2+ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate tumor immune microenvironment by decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells, thus enhancing antitumor T-cell immunity. These data illuminate a previously unrecognized antitumor mechanism of CQ, suggesting a potential new macrophage-based tumor immunotherapeutic modality.
Yoshida, T; Chou, T; Matsuda, M; Yasuhara, T; Yazaki, K; Hatano, T; Nitta, A; Okuda, T
Two new antitumor trimeric hydrolyzable tannins, woodfordin D (5) and oenothein A (13), were isolated from the dried flowers of Woodfordia fruticosa, and their macrocyclic structures, which have a novel constituent unit (woodfordinoyl group) connecting the monomers, have been elucidated on the basis of spectral and chemical evidence. Oenothein A (13) was also isolated from the leaves of Oenothera biennis.
Yoshida, T; Chou, T; Haba, K; Okano, Y; Shingu, T; Miyamoto, K; Koshiura, R; Okuda, T
Camelliin B and nobotanin I, dimeric hydrolyzable tannins of a new class having macrocyclic structures, were isolated from Camellia japonica and Heterocentron roseum, respectively. Nobotanin G and H of the structures related to nobotanin I, were also obtained from H. roseum. Camelliin B and also woodfordin C, a macrocyclic dimer from Woodfordia fruticosa, exhibited marked host-mediated antitumor activities.
Oct 20, 2008 ... hematological and antioxidant parameters in a dose dependent manner in EAC bearing mice. The results were comparable to that of the result obtained from the animals treated with the standard drug. 5-flurouracil (20 mg/kg.bw). Thus present study revealed that ETP possessed significant antitumor and.
Wagner, Julia A; Rosario, Maximillian; Romee, Rizwan; Berrien-Elliott, Melissa M; Schneider, Stephanie E; Leong, Jeffrey W; Sullivan, Ryan P; Jewell, Brea A; Becker-Hapak, Michelle; Schappe, Timothy; Abdel-Latif, Sara; Ireland, Aaron R; Jaishankar, Devika; King, Justin A; Vij, Ravi; Clement, Dennis; Goodridge, Jodie; Malmberg, Karl-Johan; Wong, Hing C; Fehniger, Todd A
NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production. Primed CD56bright cells from leukemia patients demonstrated enhanced responses to autologous blasts in vitro, and primed CD56bright cells controlled leukemia cells in vivo in a murine xenograft model. Primed CD56bright cells from multiple myeloma (MM) patients displayed superior responses to autologous myeloma targets, and furthermore, CD56bright NK cells from MM patients primed with the IL-15 receptor agonist ALT-803 in vivo displayed enhanced ex vivo functional responses to MM targets. Effector mechanisms contributing to IL-15-based priming included improved cytotoxic protein expression, target cell conjugation, and LFA-1-, CD2-, and NKG2D-dependent activation of NK cells. Finally, IL-15 robustly stimulated the PI3K/Akt/mTOR and MEK/ERK pathways in CD56bright compared with CD56dim NK cells, and blockade of these pathways attenuated antitumor responses. These findings identify CD56bright NK cells as potent antitumor effectors that warrant further investigation as a cancer immunotherapy.
Horssen, R. van; Hagen, T.L.M. ten; Eggermont, A.M.M.
Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The
bearing mice, and reduced the serum IL-4 level. The Paris saponin can inhibit U14 cell growth and prolong survival time of mice; it is speculated that the Paris saponin may express its anti-tumor activity by improving the body's immune system.
The antitumor activity was measured in DLA cell line induced mice. Inhibition of in vitro lipid peroxidation activity of the D. nobile in both liver homogenate and RBC ghosts was also carried out. The aqueous extracts of stem and flower of D. nobile showed better zone of bacterial inhibition than that of ethanol and chloroform
Abdelhakim Bouyahya; Youssef Bakri; El Ouardy Khay; Fatima Edaoudi; Ahmed Talbaoui; Abdeslam Et-Touys; Jamal Abrini; Nadia Dakka
Aromatic and medicinal plants have been traditionally used since antiquity to fight against illnesses. Recently, several researches have focused on the pharmacological properties and various bioactivities of natural products are extracted from medicinal plants, including the properties of antibacterial, antitumor and antioxidant activities. The products of medicinal plants are the secondary metabolites belonging to different compound classes such as essential oils, polyphenols,...
Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway
Full Text Available Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.
Deng, Xiangliang; Luo, Shuang; Luo, Xia; Hu, Minghua; Ma, Fangli; Wang, Yuanyuan; Zhou, Lian; Huang, Rongrong
The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.
The objective of the paper was to study the anti-tumor effect of total glycosides from Radix paeoniae rubra in S180 tumor-bearing mice, and to preliminarily explore its mechanism of action. Mice were made into S180 solid tumor model, grouped and administered with the extracts; tumor inhibition rate was measured by ...
Tsukumo, Shin-Ichi; Yasutomo, Koji
Cancer immunosurveillance is critical for the elimination of neoplastic cells. In addition, recent advances in immunological checkpoint blockade drugs have revealed the importance of the immune system in cancer treatment. As a component of the immune system, CD8 + T cells have important roles in suppressing tumors. CD8 + T cells can kill tumor cells with cytotoxic molecules, such as granzymes and perforin. IFNγ, which is produced by CD8 + T cells, can increase the expression of MHC class I antigens by tumor cells, thereby rendering them better targets for CD8 + T cells. IFNγ also has crucial functions in enhancing the antitumor abilities of other immune cells. Therefore, it has been hypothesized that antitumor immunity could be improved by modulating the activity of CD8 + T cells. The Notch pathway regulates CD8 + T cells in multiple ways. It directly upregulates mRNA expression of granzyme B and perforin, enhances differentiation toward short-lived effector cells, and maintains memory T cells. Intriguingly, CD8 + T cell-specific Notch2 deletion impairs antitumor immunity, whereas the stimulation of the Notch pathway can increase tumor suppression. In this review, we will summarize the roles of the Notch pathway in CD8 + T cells and discuss issues and implications for its use in antitumor immunity.
Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer. Mingqian Lu, Xinhua Xu, Hongda Lu, Zhongxin Lu, Bingqing Xu, Chao Tan, Kezhi Shi, Rong Guo, Qingzhi Kong ...
On 27 Feb., 2017, the World Health Organization (WHO) announced the first list of important antibiotic-resistant bacteria (http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/), which tremendously threat human-being’s health. This list included 12 kinds of bacteria that were categorized into three priority tiers: Critical, High and Medium. In the first tier, Critical, three Gram negative bacteria were included: Acinetobacter baumannii with carbapenem-resis...
Singer, R.S.; Finch, R.; Wegener, Henrik Caspar
Antibiotic-resistant bacteria were first identified in the 1940s, but while new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. Today, the excessive use of antibiotics compounded by the paucity of new agents on the market has...... meant the problem of antibiotic resistance is fast escalating into a global health crisis. There is no doubt that misuse of these drugs in human beings has contributed to the increasing rates of resistance, but recently the use of antibiotics in food animals and its consequent effect on resistance....... There is a growing concern over the transmission of resistant bacteria via the food chain. Many questions will be difficult to resolve, such as how do you distinguish the fraction of resistance in human beings that originated from animals? If we wait to see evidence that a significant amount of antibiotic resistance...
Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Maltsev, V.N.
Elimination of intestinal dysbacteriosis in irradiated animals by combining antibiotics and peparations of bifidobacteria resistant to these antibiotics prolonging the life of these animals was investigated. Broad spectrum antibiotics are used to treat intestinal dysbacteriosis. Bifidobacterial preparations are used to restore the microbial cenosis and their administration 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 bifidobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. Use of antibiotics alone could be the cause of intestinal dysbacteriosis
Silverman, Michael A.; Konnikova, Liza; Gerber, Jeffrey S.
Summary Antibiotics induce changes or dysbiosis of the intestinal microbiome. These antibiotic-induce changes may contribute to the pathogenesis of necrotizing enterocolitis (NEC) and antibiotic-associated diarrhea (AAD). Studies are beginning to unravel the contribution of specific groups of microbes to these diseases—most notably Gammaproteobacteria for NEC and bile acid- and carbohydrate-metabolizing microbes for AAD. Antibiotic-associated diarrhea occurs when antibiotic treatment induces diarrhea by altering the metabolic function of the patient’s intestinal microbiota leading to either an osmotic or infectious diarrhea, most notably Clostridium difficile infection (CDI). Antibiotic therapy impairs the host microbiota’s ability to resist colonization or expansion of pathogenic bacteria. In the case of CDI, there is growing evidence that microbiota-mediated bile acid metabolism is critical in the pathogenesis of this infection. Probiotics or other microbiota-targeted therapies may provide effective strategies to prevent and treat NEC and AAD. PMID:28164853
Full Text Available Abstract Background Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV. Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. Methods Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. Results All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: G. vaginalis strains were also susceptible for clindamycin ( 256 μg/ml but susceptible to clindamycin (0.023 – 0.125 μg/ml. Conclusion Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains.
Hrivnák, R; Hanke, I; Hansliánová, M; Kala, Z; Sevcíková, A
Antibiotic (ATB) prophylaxis is generaly recommended in surgery. There is an important role in colorectal surgery especially. Colorectal surgery is associated with a particularly high risk of post-operative infection because of contamination of the wound with faecal bacteria. ATB prophylaxis decreases surgical wound infection, morbidity and mortality as well. Morbidity and mortality are associated with longer hospital stays and increased costs of care. At surgical department of Faculty hospital Brno, during March-June 2008 an 88 patients were operated because of different diagnoses in colorectum. Both an emergent and schedule operations were made. Type of ATBs, time of application before operation, reapplication after operation and surgical site infection (SSI), in - hospital stay were followed up prospectively. SSI were divided into superficial, deep and intraabdominal. Data were analyse statistically. The most used combination of ATBs, almost in 91%, were Cefazoline and Metronidazole. In 50% were time of application till 20 minutes before incision. Only in 17% were time of application in interval 20-30 minutes before incision, which is recommended. We noticed 25 SSI. We prove that patients with SSI has almost two-times longer in-hospital stay. Enterococcus and enterobacterias were the most common etiological agents. ATB prophylaxis is indicated in colorectal surgery. It has to be applied in correct dose and right time before operation to decrease SSI.
Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.
Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.
Full Text Available To successfully prepare fluorouracil–chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil–chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU–CS–mPEG prodrugs, and infrared, 1H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad
Cakar, Jasmina; Parić, Adisa; Maksimović, Milka; Bajrović, Kasim
Broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)] contains substantial quantities of bioactive compounds, which are good free radical scavengers and thus might have strong antitumor properties. Enhancing production of plant secondary metabolites could be obtained with phytohormones that have significant effects on the metabolism of secondary metabolites. In that manner, in vitro culture presents good model for manipulation with plant tissues in order to affect secondary metabolite production and thus enhance bioactive properties of plants. Estimation of the antioxidative and antitumor properties of broccoli cultivated in different in vitro conditions. In vitro germinated and cultivated broccoli seedlings, as well as spontaneously developed calli, were subjected to Soxhlet extraction. Antioxidative activity of the herbal extracts was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) radical method. Antitumor properties of the extracts were determined using crown-gall tumor inhibition (potato disc) assay. Three, 10, 20, and 30 days old broccoli seedlings, cultivated in vitro on three different Murashige-Skoog media, two types of callus, and seedlings from sterile filter paper were used for extraction. In total, 15 aqueous extracts were tested for antioxidative and antitumor potential. Three day-old seedlings showed the highest antioxidative activity. Eleven out of 15 aqueous extracts demonstrated above 50% of crown-gall tumor inhibition in comparison with the control. Tumor inhibition was in association with types and concentrations of phytohormones presented in growing media. It is demonstrated that phytohormones in plant-growing media could affect the bioactive properties of broccoli either through increasing or decreasing their antioxidative and antitumor potential.
Full Text Available Abstract Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.
Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.
Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)
Kristian Michael Hargadon
Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor
Full Text Available Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7 and normal (MCF10A cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay and analysis of morphological cell changes (Fluorescence microscopy. The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml. Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential.
Hargadon, Kristian M
Dendritic cells (DC) are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programing of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor immunity.
Olesen, Scott; Barnett, Michael; MacFadden, Derek; Lipsitch, Marc; Grad, Yonatan H
Abstract Background Antibiotic consumption is considered a major driver of antibiotic resistance, but it remains unclear whether the consumption–resistance relationship is apparent for many organisms and drugs, and whether aggregate consumption is the best predictor of resistance. Methods We conducted a landscape assessment of the consumption-resistance relationship by comparing a 20% sample of Medicare Part D outpatient antibiotic pharmacy claims with a nationwide survey of hospital antibiotic susceptibility reports. Antibiotic consumption was summarized in individual states and hospital-referral regions (HRRs) using traditional, aggregate consumption or by metrics that account for the concentration of consumption in a few individuals (Gini coefficient). The consumption–resistance relationships for 17 organism–drug combinations were simultaneously evaluated (Spearman’s rho; linear models predicting resistance from aggregate consumption and Gini coefficient) and corrected for multiple-hypothesis testing (Benjamini–Hochberg). Results We identified a significant correlation between aggregate consumption of an antibiotic and an organism’s reported resistance to that antibiotic in only a few cases: quinolones and E. coli (Spearman’s rho = 0.65, adjusted P < 10−4) and E. cloacae (rho = 0.50, adjusted P = 0.006). In other cases, notably E. coli with trimethoprim–sulfamethoxazole, the distribution of antibiotic consumption among consumers has a marginal relationship with antibiotic resistance (−1.0 p.p. resistance per p.p. Gini coefficient of consumption among consumers, unadjusted P < 0.001). Conclusion There is a clear correlation between aggregate consumption of an antibiotic and resistance of an organism to that antibiotic in only a few cases, suggesting that antibiotic steward efforts might maximize their effectiveness by focusing on particular organisms, drugs, and consumer groups rather than overall, aggregate consumption
Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera
Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, by disrupting the intricate balance between specific bacterial groups within this ecosystem...... 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...
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.
Palmer, Lucy B
Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.
... GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Health Topics → Antibiotic Resistance URL of this page: https://medlineplus.gov/antibioticresistance. ...
-antibiotics to control bacterial colonization and infection and potentially ... different approaches were used to combine antibacterial materials to achieve desirable effects. Nanocarriers, such as pH-sensitive nanoparticles, may.
Molecular analysis and antibiotic resistance investigation of Staphylococcus aureus isolates associated with staphylococcal food poisoning and nosocomial infections. Y Zhang, S Cheng, G Ding, M Zhu, X Pan, L Zhang ...
Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as 'the biology of history': the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today.
Broad-spectrum antibiotics are commonly used by physicians to treat various infections. The source of infection and causative organisms are not always apparent during the initial evaluation of the patient, and antibiotics are often given empirically to patients with suspected sepsis. Fear of attempting cephalosporins and carbapenems in penicillin-allergic septic patients may result in significant decrease in the spectrum of antimicrobial coverage. Empiric antibiotic therapy should sufficiently cover all the suspected pathogens, guided by the bacteriologic susceptibilities of the medical center. It is important to understand the major pharmacokinetic properties of antibacterial agents for proper use and to minimize the development of resistance. In several septic patients, negative cultures do not exclude active infection and positive cultures may not represent the actual infection. This article will review the important differences in the spectrum of commonly used antibiotics for nosocomial bacterial infections with a particular emphasis on culture-negative sepsis and colonization.
The second part of a series of three news features on antimicrobial resistance looks at how the antibiotics pipeline is drying up while resistance to existing drugs is increasing. Theresa Braine reports.
(26). Prevention of emergence of antibiotic resistance during treatment is therefore an important goal when prescribing antimicrobials. Problems affecting the operation of laboratories at the peripheral level are widespread.
Fiore, David C; Fettic, Lacy P; Wright, Stephanie D; Ferrara, Bonnie R
Despite universal agreement that antibiotic overprescribing is a problem, the practice continues to vex us. Antibiotic use--whether appropriate or not--has been linked to rising rates of antimicrobial resistance, disruption of the gut microbiome leading to Clostridium difficile infections, allergic reactions, and increased health care costs. And yet, physicians continue to overprescribe this class of medication. A 2016 Centers for Disease Control and Prevention report estimates that at least 30% of antibiotics prescribed in US outpatient settings are unnecessary. Another report cites a slightly higher figure across a variety of health care settings. Pair these findings with the fact that there are currently few new drugs in development to target resistant bacteria, and you have the potential for a post-antibiotic era in which common infections could become lethal. Family practitioners are on the front lines of this battle. Here's what we can do now.
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. PMID:25199988
... 300 million to bring a new antibiotic to market. Many efforts to find novel drugs in fungi ... sulbactam are already in use for blocking the beta-lactamase enzymes that destroy the penicillin family of ...
Haaber, Jakob; Penadés, José R; Ingmer, Hanne
Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic...... of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen. Staphylococcus aureus cells...... are effective in exchanging mobile genetic elements, including antibiotic-resistance genes.During colonization or infection of host organisms, the exchange appears to be particularly effective.Bacteriophage-mediated transfer involves both transduction and autotransduction, which may enable lysogenic S. aureus...
Abdul-Moqueet, Mohammad M.
The effect of weak electromagnetic fields on the interaction of the antibiotic erythromycin on E.coli has been studied. Erythromycin is a first derivative antibiotic which is bacteriostatic in nature. E.coli's structure has been well studied and provides a baseline for understanding the interaction. Electromagnetic fields are shown to influence the growth curve of bacterium depending on the field's geometry. The theoretical model discussed in this thesis describes the interaction using a two-fluid model. The basis of this two-fluid model has been tested and shown that the concentration of antibiotics in the fluid environment is proportional to the response seen by the bacterium. The response of the bacterium has been determined using optical density measurements from which the behavior of the antibiotic-cell system has been studied.
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
Abstract. Purpose: To evaluate the practice of self-medication and evaluate the knowledge of rational use of antibiotics among ... rational use of antibiotics. Keywords: Antibiotics, Self-medication, Rational use, Undergraduate students, Awareness ..... behavioral factors leading to acquired bacterial resistance to antibiotics in ...
Antibiotic resistance in food animals has received increased scrutiny in recent years due to the increased prevalence of antibiotic resistant infections in the human clinical setting. The extent to which antibiotic usage in food animals is responsible for the burden of antibiotic resistance in human...
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, ...
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.
Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra
The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Draenert, R; Seybold, U; Grützner, E; Bogner, J R
Therapeutic efficacy and safety in infections due to multidrug-resistant bacteria can be improved by the clinical development of new compounds and devising new derivatives of already useful antibiotics. Due to a striking global increase in multidrug-resistant Gram-positive but even more Gram-negative organisms, new antibiotics are urgently needed. This paper provides a review of novel antibiotic compounds which are already in clinical development, mainly in phase III clinical trials. Each of these new trials increases the possibility of new antibiotics receiving approval.
Beatriz Espinosa Franco; Marina Altagracia Martínez; Martha A Sánchez Rodríguez; Albert I Wertheimer
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...
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....
Kim, Min Kyoung; Chuang, Sung-Kiang; August, Meredith
This study assessed the antibiotic resistance profile in patients with severe orofacial infections treated at a single institution from 2009 through 2014. Factors contributing to resistance were studied. The resistance profile was compared with that of a cohort of similar patients treated a decade previously to identify changes in antibiotic resistance. In addition, the effect of antibiotic resistance on in-hospital course was studied. This was a 5-year retrospective cohort study. Patients were identified through the oral and maxillofacial surgery data registry. Inclusion criteria were patients treated for orofacial infection requiring hospital admission, surgical drainage, and availability of complete medical, surgical, and microbiological data. Patients with incomplete data or treated as outpatients or nonsurgically were excluded. Sixty patient charts were identified for review. Demographic data; medical, dental, and surgical histories; and hospital course and treatment specifics were obtained for each patient. Linear regression and logistic analyses were used to analyze the data. Men composed 60% of the cohort (mean age, 45 yr). Average hospital stay was 5.5 days. Penicillin resistance was found in 32.5% of aerobic isolates and clindamycin resistance was found in 29.3%. Streptococcus viridans and Staphylococcus species showed increased resistance to clindamycin and erythromycin compared with historic controls. Younger patient age, surgical history, and number of cultured aerobes showed a relevant correlation to antibiotic resistance. The need for changes in antibiotics, repeat surgical drainage, and increased serum urea nitrogen levels correlated with longer hospital stay. A serious increase in clindamycin and erythromycin resistance was found for S viridans and Staphylococcus species. Age, surgical history, and number of cultured aerobes showed a statistically meaningful correlation to antibiotic resistance. Presence of antibiotic resistance failed to show
Actinobacteria are important members of the soil ecosystems, where they are involved in organic matter decomposition. It is worth mentioning that their secondary metabolism allows them to produce a variety of different compounds. These compounds include antibiotics, among them aminoglycosides have a place in clinical practice. These antibiotics are significant due to a broad spectrum of activities against both gram-negative and gram-positive bacteria. However, their use currently carries a ri...
Mesut OgrendikDivision Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in t...
Full Text Available Introduction: Antibiotics represent the most prescribed class of medication in the pediatric circles. Almost 50% of the medication was prescribed without definite merit. Recently published studies have shown that the level of knowledge, awareness, as well as parents' expectations, play a significant role in the amount of prescribed antibiotics by pediatricians. Aim: To assess the level of parent's education, attitude and behavior, in regard to antibiotic use in pediatric population in Serbia. Material and methods: The cross-sectional study was performed between October 2015 and February 2016. An anonymous survey approach had been used. Demographic data of the participants gave an insight in the level of knowledge and common practice regarding the use of antibiotics in children. The data collected was analyzed by methods of descriptive and analytic statistics. Results: Of 850 recruited, 763 completed and returned the survey. A high level of knowledge was found in 79.5% of the participants. The highest percent of parents answered the questions correctly in regard to reporting drug-related adverse reactions, including allergic reactions (99% and 93% respectively. Almost one third (27% of the parents thought that antibiotics can cure viral infections. More than 20% of participants thought that antibiotics can control pain, and that more expensive medication was more effective. The worrisome is the fact that 15% bought antibiotic at least once without a doctor's prescriptions, while 18% stashed away leftovers for later use. Conclusion: Although study results showed good quality data, parents are still deciding by themselves if they should start antibiotic therapy. Reinforcing established educational programs and encouraging communication with their pediatrician would be highly justified.
He, Xiao-Zheng; Wang, Qi-Fu; Han, Shuai; Wang, Hui-Qing; Ye, Yong-Yi; Zhu, Zhi-Yuan; Zhang, Shi-Zhong
In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3(+) and CD4(+)T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs) were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs). Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition. DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo-ablation showed weak anti-tumor immunity, only inhibiting the growth of rechallenged tumors. But many IL-10-low DCs, rather than IL-10-high DCs, infiltrated the tumors. More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo. Cryo-ablation could recover function of tumor induced tolerogenic DCs in vitro; and depletion of Tregs could improve this anti-tumor effect in vivo. The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.
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.
Full Text Available Antibiotic resistance represents a serious threat to public health worldwide, leading to increased healthcare costs, prolonged hospital stays, treatment failures and deaths. To address the emergency of multidrug-resistance, the major international societies of infectious diseases and public health have developed strategies and guidelines to reduce unnecessary antimicrobial use as well as to incite the development of new antibiotics targeting multidrug-resistant pathogens. Even though pharmaceutical companies have been developing new antibiotics since 2010, the global situation is still worrisome. Indeed, the currently available data regarding new antibiotics are limited to microbiological activity and pharmacokinetic profile and their use for the treatment of life-threatening infections (i.e., sepsis is often off-label. The aim of this article is to present the antibiotic molecules recently commercialized and with which clinicians will deal quite often in next years. We describe ceftolozane/tazobactam, ceftazidime/avibactam, eravacycline, plazomicin, dalbavancin, oritavancin and tedizolid in terms of mechanism of action, antimicrobial spectrum, trials behind the approval and possible indications for the future. In last few years, the US Food and Drug Administration (FDA and the European Medicines Agency (EMA approved many new antibiotic molecules but, unfortunately, they lack in biological innovation and in wide clinical indications. These agents show appealing properties for off-label use, as we propose in the article, but caution is still needed considering that high-quality clinical data are limited.
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.
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.
Hughes, Diarmaid; Karlén, Anders
Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.