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Sample records for cytotoxic colchicine ring

  1. Lymphocyte cytotoxicity of colchicine in Hiroshima atomic bomb survivors

    International Nuclear Information System (INIS)

    Caplan, R.A.; Odoroff, C.L.; Ozaki, Kyoko; Hamilton, H.B.; Finch, S.C.

    1979-07-01

    The cytotoxicity of colchicine for the peripheral blood lymphocytes of 151 Hiroshima atomic bomb survivors and their controls was determined. No radiation effect was found, but modest age-related changes for the initial number of vialble cells and for the cytotoxicity of colchicine were observed. (author)

  2. Colchicine

    Science.gov (United States)

    ... familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, ... emergency room immediately. Taking too much colchicine may cause death.Symptoms ... sore throat, fever, chills, and other signs of infection paleness or ...

  3. N-acetylcolchinol O-methyl ether and thiocolchicine, potent analogs of colchicine modified in the C ring. Evaluation of the mechanistic basis for their enhanced biological properties

    International Nuclear Information System (INIS)

    Kang, G.J.; Getahun, Z.; Muzaffar, A.; Brossi, A.; Hamel, E.

    1990-01-01

    Two colchicine analogs with modifications only in the C ring are better inhibitors than colchicine of cell growth and tubulin polymerization. Radiolabeled thiocolchicine (with a thiomethyl instead of a methoxy group at position C-10) and N-acetylcolchinol O-methyl ether (NCME) (with a methoxy-substituted benzenoid instead of the methoxy-substituted tropone C ring) were prepared for comparison with colchicine. Scatchard analysis indicated a single binding site with KD values of 1.0-2.3 microM. Thiocolchicine was bound 2-4 times as rapidly as colchicine, but the activation energies of the reactions were nearly identical (18 kcal/mol for colchicine, 20 kcal/mol for thiocolchicine). NCME bound to tubulin in a biphasic reaction. The faster phase was 60 times as fast as colchicine binding at 37 degrees C, and a substantial reaction occurred at 0 degrees C. The rate of the faster phase of NCME binding changed relatively little as a function of temperature, so the activation energy was only 7.0 kcal/mol. Dissociation reactions were also evaluated, and at 37 degrees C the half-lives of the tubulin-drug complexes were 11 min for NCME, 24 h for thiocolchicine, and 27 h for colchicine. Relative dissociation rates as a function of temperature varied little among the drug complexes. Activation energies for the dissociation reactions were 30 kcal/mol for thiocolchicine, 27 kcal/mol for NCME, and 24 kcal/mol for colchicine. Comparison of the activation energies of association and dissociation yielded free energies for the binding reactions of -20 kcal/mol for NCME, -10 kcal/mol for thiocolchicine, and -6 kcal/mol for colchicine. The greater effectiveness of NCME and thiocolchicine as compared with colchicine in biological assays probably derives from their more rapid binding to tubulin and the lower free energies of their binding reactions

  4. Colchicine: old and new.

    Science.gov (United States)

    Slobodnick, Anastasia; Shah, Binita; Pillinger, Michael H; Krasnokutsky, Svetlana

    2015-05-01

    Although colchicine has been a focus of research, debate, and controversy for thousands of years, the US Food and Drug Administration just approved it in 2009. Over the past decade, advances in the knowledge of colchicine pharmacology, drug safety, and mechanisms of action have led to changes in colchicine dosing and to potential new uses for this very old drug. In this review, we discuss the pharmacologic properties of colchicine and summarize what is currently known about its mechanisms of action. We then discuss and update the use of colchicine in a variety of illnesses, including rheumatic and, most recently, cardiovascular diseases. Published by Elsevier Inc.

  5. Uptake of [3H]colchicine into brain and liver of mouse, rat, and chick

    International Nuclear Information System (INIS)

    Bennett, E.L.; Alberti, M.H.; Flood, J.F.

    1981-01-01

    The uptake of [ring A-4- 3 H] colchicine and [ring C-methoxy- 3 H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy- 3 H] and [ring A- 3 H]colchicine was also studied in rats. The general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkaloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments, support the hypotheses that structural alterations in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation

  6. UPTAKE OF [3H]-COLCHICINE INTO BRAIN AND LIVER OF MOUSE, RAT, AND CHICK

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Edward L.; Alberti, Marie Hebert; Flood, James F.

    1980-07-01

    The uptake of [ring A-4-{sup 3}H] colchicine and [ring C-methoxy-{sup 3}H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy-{sup 3}H] and [ring A-{sup 3}H]colchicine was also studied in rats. the general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkoloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments [7], support the hypotheses that structural alteration in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation.

  7. Fatal colchicine intoxication

    Directory of Open Access Journals (Sweden)

    Smael Labib

    2014-01-01

    Full Text Available Colchicine is an alkaloid extracted from autumnal Colchicum plant which is used primarily for its anti-inflammatory therapy effect. Acute intoxication with colchicine is uncommon but often severe and results in multiple visceral organ dysfunctions. The intoxication severity and mortality are directly depending on the ingested dose. The treatment is manly symptomatic. However, the development of specific anti-colchicine immunotherapy would offer a new therapeutic perspective. Authors report a case of a young patient that ingested 40 tablets colchicine, which caused a multiple organ failure and with fatal outcome.

  8. A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT-116 colon cancer cells.

    Science.gov (United States)

    Kumar, Ashok; Singh, Baljinder; Sharma, Parduman R; Bharate, Sandip B; Saxena, Ajit K; Mondhe, D M

    2016-03-01

    Colchicine is a tubulin-binding natural product isolated from Colchicum autumnale. Here we report the in vitro anticancer activity of C-ring modified semi-synthetic derivative of colchicine; N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(4-phenyl-piperidin-1-yl)-5,6,7,9 tetrahydrobenzo[a]heptalen-7-yl]acetamide (4h) on colon cancer HCT-116 cell line. The compound 4h was screened for anti-proliferative activity against different human cancer cell lines and was found to exhibit higher cytotoxicity against colon cancer cell lines HCT-116 and Colo-205 with IC50 of 1 and 0.8 μM respectively. Cytotoxicity of the compound to the normal fR2 breast epithelial cells and normal HEK293 human embryonic kidney cells was evaluated in concentration and time-dependent manner to estimate its selectivity for cancer cells which showed much better selectivity than that of colchicine. Compound 4h induced cell death in HCT-116 cells by activating apoptosis and autophagy pathways. Autophagy inhibitor 3-MA blocked the production of LC3-II and reduced the cytotoxicity in response to 4h, but did not affect apoptosis, suggesting thereby that these two were independent events. Reactive oxygen species scavenger ascorbic acid pretreatment not only decreased the reactive oxygen species level but also reversed 4h induced cytotoxicity. Treatment with compound 4h depolymerized microtubules and the majority of cells arrested at the G2/M transition. Together, these data suggest that 4h has better selectivity and is a microtubule depolymerizer, which activates dual cell-death machineries, and thus, it could be a potential novel therapeutic agent in cancer therapy. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy.

    Science.gov (United States)

    Bhattacharya, Surela; Das, Amlan; Datta, Satabdi; Ganguli, Arnab; Chakrabarti, Gopal

    2016-08-01

    Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of colchicine against cancer is limited by its toxicity against normal cells. But, there is no report of its cytotoxic potential against lung cancer cell, at clinically permissible or lower concentrations, minimally toxic to non-cancerous cells. Hence, in the present study, we investigated the possible mechanism by which the efficacy of colchicine against lung cancer cells at less toxic dose could be enhanced. Colchicine at clinically admissible concentration of 2.5 nM had no cytotoxic effect and caused no G2/M arrest in A549 cells. However, at this concentration, colchicine strongly hindered the reformation of cold depolymerised interphase and spindle microtubule. Colchicine induced senescence and reactive oxygen species mediated autophagy in A549 cells at this concentration. Autophagy inhibitor 3-methyladenine (3-MA) sensitised the cytotoxicity of colchicine in A549 cells by switching senescence to apoptotic death, and this combination had reduced cytotoxicity to normal lung fibroblast cells (WI38). Together, these findings indicated the possible use of colchicine at clinically relevant dose along with autophagy inhibitor in cancer therapy.

  10. Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings.

    Science.gov (United States)

    Yamauchi, Satoshi; Wukirsari, Tuti; Ochi, Yoshiaki; Nishiwaki, Hisashi; Nishi, Kosuke; Sugahara, Takuya; Akiyama, Koichi; Kishida, Taro

    2017-09-01

    The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC 50 =12μM), however, it was inactive against HeLa cells (EC 50 >100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC 50 values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC 50 value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference. Copyright © 2017. Published by Elsevier Ltd.

  11. Colchicine for pericarditis.

    Science.gov (United States)

    Alabed, Samer; Cabello, Juan B; Irving, Greg J; Qintar, Mohammed; Burls, Amanda

    2014-08-28

    Pericarditis is the inflammation of the pericardium, the membranous sac surrounding the heart. Recurrent pericarditis is the most common complication of acute pericarditis, causing severe and disabling chest pains. Recurrent pericarditis affects one in three patients with acute pericarditis within the first 18 months. Colchicine has been suggested to be beneficial in preventing recurrent pericarditis. To review all randomised controlled trials (RCTs) that assess the effects of colchicine alone or combined, compared to any other intervention to prevent further recurrences of pericarditis, in people with acute or recurrent pericarditis. We searched the following bibliographic databases on 4 August 2014: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of 12, 2014 on The Cochrane Library), MEDLINE (OVID, 1946 to July week 4, 2014), EMBASE (OVID, 1947 to 2014 week 31), and the Conference Proceedings Citation Index - Science on Web of Science (Thomson Reuters) 1990 to 1 Aug 2014. We did not apply any language or time restrictions. RCTs of people with acute or recurrent pericarditis who are receiving colchicine compared to any other treatment, in order to prevent recurrences. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The first primary outcome was the time to recurrence, measured by calculating the hazard ratios (HRs). The second primary outcome was the adverse effects of colchicine. Secondary outcomes were the rate of recurrences at 6, 12 and 18 months, and symptom relief. We included four RCTs, involving 564 participants in this review. We compared the effects of colchicine in addition to a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen, aspirin or indomethacin to the effects of the NSAID alone. Two comparable trials studied the effects of colchicine in 204 participants with recurrent pericarditis and two trials studied 360 people with acute pericarditis. All trials had a

  12. Biotherapeutic potential and mechanisms of action of colchicine.

    Science.gov (United States)

    Dubey, Kashyap Kumar; Kumar, Punit; Labrou, Nikolaos E; Shukla, Pratyoosh

    2017-12-01

    Cancer is a clinical situation caused by uncontrolled cell division and is responsible for a large number of deaths worldwide. Colchicine is a classical antimitotic, tubulin-binding agent (TBA) which is being explored for its antitumor activities, although its tubulin-binding ability leads to some toxicity toward normal cells proliferation. Colchicine derivatives are considered as potent antitumor compounds with less toxicity compared to colchicine. Derivatives with substituted functional groups at A-ring (methoxy), B-ring (acetamide) or C-ring (methoxy) have been synthesized via chemical and microbial routes and show modified bioactivities and altered tropolonic functionality. Earlier reports, in combination with our group's research findings, suggest that microbial biotransformation is an efficient choice for the production of bioactive colchicine derivatives. This route has gained significant interest in the mass production of regio-specific, cost-effective, safe and eco-friendly derivatives. The present review paper critically analyzes and discusses the development and application of colchicine derivatives as a potent antitumor molecule and their production through a microbial transformation process. The information provided in this review might assist in the stimulation of new ideas regarding the development of alternative therapeutic agent(s) for cancer treatment.

  13. Upstream biomanufacturing of pharmaceutical colchicine.

    Science.gov (United States)

    Sivakumar, Ganapathy

    2018-02-01

    The plant-based colchicine potentially affects major diseases such as cardiovascular events, cancers and gout. Gloriosa superba seeds are a conventional pharmaceutical source of colchicine. The demand for pharmaceutical-grade colchicine has increased due to the shortage of feasible upstream manufacturing, encompassing all stages in the processes of biosynthesis and biomanufacturing before the raw material is ready for purification. Consequently, developing sustainable upstream industrial colchicine biofactories is imperative, especially in curtailing drug costs. A new upstream bioprocess has been established, using specialized biorhizomes with comprehensive specific-enzymes that catalyze the construction of biogenic functionalized intermediates that are converted into colchicine. This review emphasizes a novel biorhizome approach for biomanufacturing pharmaceutical-grade natural colchicine, a biosynthetic pathway elucidation and its challenges to synthetic biotechnology.

  14. Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors

    Science.gov (United States)

    Salum, Lívia B.; Altei, Wanessa F.; Chiaradia, Louise D.; Cordeiro, Marlon N.S.; Canevarolo, Rafael R.; Melo, Carolina P.S.; Winter, Evelyn; Mattei, Bruno; Daghestani, Hikmat N.; Santos-Silva, Maria Cláudia; Creczynski-Pasa, Tânia B.; Yunes, Rosendo A.; Yunes, José A.; Andricopulo, Adriano D.; Day, Billy W.; Nunes, Ricardo J.; Vogt, Andreas

    2013-01-01

    Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. PMID:23524161

  15. Colchicine for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Gong, Yan; Gluud, Christian

    2005-01-01

    Colchicine is used for patients with primary biliary cirrhosis due to its immunomodulatory and antifibrotic potential. The results from randomized clinical trials have, however, been inconsistent. We conducted a systematical review to evaluate the effect of colchicine for primary biliary cirrhosis....

  16. Compound list: colchicine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available colchicine COL 00113 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/colchicine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/colchicine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/colchicine...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/colchicine.Rat.in_vivo.Liver.Repeat.zip ...

  17. Colchicine prodrugs and codrugs: Chemistry and bioactivities.

    Science.gov (United States)

    Ghawanmeh, Abdullah A; Chong, Kwok Feng; Sarkar, Shaheen M; Bakar, Muntaz Abu; Othaman, Rizafizah; Khalid, Rozida M

    2018-01-20

    Antimitotic colchicine possesses low therapeutic index due to high toxicity effects in non-target cell. However, diverse colchicine analogs have been derivatized as intentions for toxicity reduction and structure-activity relationship (SAR) studying. Hybrid system of colchicine structure with nontoxic biofunctional compounds modified further affords a new entity in chemical structure with enhanced activity and selectivity. Moreover, nanocarrier formulation strategies have been used for colchicine delivery. This review paper focuses on colchicine nanoformulation, chemical synthesis of colchicine prodrugs and codrugs with different linkers, highlights linker chemical nature and biological activity of synthesized compounds. Additionally, classification of colchicine prodrugs based on type of conjugates is discussed, as biopolymers prodrugs, fluorescent prodrug, metal complexes prodrug, metal-labile prodrug and bioconjugate prodrug. Finally, we briefly summarized the biological importance of colchicine nanoformulation, colchicine prodrugs and codrugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Anticancer Effects of Colchicine on Hypopharyngeal Cancer.

    Science.gov (United States)

    Cho, Jung Hae; Joo, Young Hoon; Shin, Eun Young; Park, Eun Ji; Kim, Min Sik

    2017-11-01

    Colchicine is an alkaloid widely used for the treatment of inflammatory diseases, such as gout. It suppresses cell division by inhibiting mitosis. We investigated the anticancer effects of colchicine on human hypopharyngeal cancer cells and the mechanisms underlying its anticancer effects. XTT cell proliferation assay showed that colchicine inhibited the growth and proliferation of human hypopharyngeal cancer cells (FaDu and SNU1041) in a dose- and time-dependent manner. Colchicine also inhibited the migration, invasion, and adhesion of hypopharyngeal cancer cells in a dose-dependent manner. The levels of mRNA expression and activity of matrix metalloproteinase-9 (MMP9) and urokinase-type plasminogen activator (uPA) decreased after treatment with colchicine. Further investigation revealed that colchicine inhibited the phosphorylation of the FAK/SRC complex and paxillin. Tumor volume ratios in colchicine-treated mice (0.1 mg/kg, every 2 days for 14 days) increased less than in control mice. To our knowledge, this is the first report showing that colchicine can suppress cell invasion, migration, and adhesion through reduced expression of MMP9, the uPA system, and the FAK/SRC complex. Colchicine has the potential to prevent disease progression in hypopharyngeal cancer and may have application as an adjunctive treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Colchicine-Induced Rhabdomyolysis: An Autopsy Case.

    Science.gov (United States)

    Arslan, Murat Nihat; Özgün, Ayşe; Daş, Taner; Kumru, Durmuş; Şam, Bülent; Koç, Sermet

    2016-06-01

    Colchicine is derived from Colchicum autumnale and Gloriosa superba and is used to treat acute gout and familial Mediterranean fever (FMF). Musculoskeletal adverse effects range from myopathy to rhabdomyolysis. An 18-year-old woman, with a 2-year history of FMF treated with colchicine, took 9 colchicine pills (4.5 mg) to relieve severe abdominal pain. On the sixth day of hospitalization, the patient's condition worsened, and she died. As this was a case of fatal poisoning, a forensic autopsy was performed, and the cause of death was determined to be complications of muscle destruction due to colchicine intoxication with the findings of myocytolysis, positive antimyoglobin antibody staining kidney tubules. Colchicine toxicity begins with gastrointestinal symptoms. Multiorgan effects follow the gastrointestinal effects. Serious outcomes of colchicine toxicity are rhabdomyolysis, bone marrow suppression, and disseminated intravascular coagulation. In chronic diseases that require lifelong treatment with medications, adverse effects can arise with long periods of use. Our patient had been treated for FMF with colchicine for 2 years but took too many colchicine pills to relieve her severe abdominal pain. Warning patients about the effects of high doses of drugs and providing information about their toxic effects and what to do "in case" of overuse could be lifesaving.

  20. Multi-orgaanfalen door colchicine-intoxicatie

    NARCIS (Netherlands)

    Schut, N. H.; Romijn, J. A.

    1990-01-01

    A 61-year-old woman was admitted because of colchicine intoxication. After a period with gastrointestinal symptoms multiple organ failure and secondary septicaemia developed. The patient died of irreversible shock. The pharmacology of colchicine and the clinical manifestations and therapy of

  1. Preliminary study on the inducement effect of colchicine during ...

    African Journals Online (AJOL)

    This is the first report of colchicine treatment effect on microsporogenesis of Ginkgo biloba L, By high performance liquid chromatography (HPLC) analysis, colchicine was detected in microsporocyte inclusion from colchicine-treated microsporangium and microsporocyte of G. biloba, The change amount of colchicine was ...

  2. Colchicine for primary biliary cirrhosis. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Gong, Y; Gluud, C

    2003-01-01

    Colchicine has been used for patients with primary biliary cirrhosis because of its immunomodulatory and antifibrotic potential. The therapeutical responses to colchicine in randomised clinical trials were inconsistent.......Colchicine has been used for patients with primary biliary cirrhosis because of its immunomodulatory and antifibrotic potential. The therapeutical responses to colchicine in randomised clinical trials were inconsistent....

  3. Colchicine: an ancient drug with novel applications.

    Science.gov (United States)

    Dasgeb, B; Kornreich, D; McGuinn, K; Okon, L; Brownell, I; Sackett, D L

    2018-02-01

    Colchicine is a treatment for gout that has been used for more than a millennium. It is the treatment of choice for familial Mediterranean fever and its associated complication, amyloidosis. The 2009 U.S. Food and Drug Administration approval of colchicine as a new drug had research consequences. Recent investigations with large cohorts of patients with gout who have been taking colchicine for years have demonstrated novel applications within oncology, immunology, cardiology and dermatology. Some emerging dermatological uses include the treatment of epidermolysis bullosa acquisita, leucocytoclastic vasculitis, aphthous stomatitis and others. In this work we relate the history and the new horizon of this ancient medicine. © 2017 British Association of Dermatologists.

  4. p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

    Science.gov (United States)

    Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

    2016-07-25

    We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

  5. Improved Growth And Colchicine Concentration In Gloriosa Superba ...

    African Journals Online (AJOL)

    AM), fungi, Glomus mossae, Glomus fasciculatum, Gigaspora margarita and Gigaspora gilmorei either alone or supplemented with P-fertilizer, on colchicine concentration in Gloriosa superba were studied. The concentration of colchicine was ...

  6. Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine.

    Science.gov (United States)

    Guo, Xiucai; Lin, Dongju; Li, Weiwei; Wang, Kai; Peng, Ying; Zheng, Jiang

    2016-03-21

    Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10-DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ.

  7. Effect of water stress on growth of colchicine induced polyploid ...

    African Journals Online (AJOL)

    Polyploid induction was conducted by different colchicine concentration with seedlings of Coccinia palmata and Lagenaria sphaerica. Colchicine induced polyploid seedlings were grown in pots and subjected to varying levels of irrigation until they reached a flowering stage. The survival rate was best at colchicine ...

  8. Colchicine for prevention of cardiovascular events.

    Science.gov (United States)

    Hemkens, Lars G; Ewald, Hannah; Gloy, Viktoria L; Arpagaus, Armon; Olu, Kelechi K; Nidorf, Mark; Glinz, Dominik; Nordmann, Alain J; Briel, Matthias

    2016-01-27

    Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations. To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with high cardiovascular risk. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data. Randomised controlled trials (parallel-group or cluster design or first phases of cross-over studies) comparing colchicine over at least six months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non-scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. . We included 39 randomised parallel-group trials with 4992 participants. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I² = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I

  9. Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel

    Directory of Open Access Journals (Sweden)

    Uppal Sonal O

    2006-06-01

    Full Text Available Abstract Background Tumor promoters enhance tumor yield in experimental animals without directly affecting the DNA of the cell. Promoters may play a role in the development of cancer, as humans are exposed to them in the environment. In work based on computer-assisted microscopy and sophisticated classification methods, we showed that cells could be classified by reference to a database of known normal and cancerous cell phenotypes. Promoters caused loss of properties specific to normal cells and gain of properties of cancer cells. Other compounds, including colchicine, had a similar effect. Colchicine given together with paclitaxel, however, caused cells to adopt properties of normal cells. This provided a rationale for tests of microtubule inhibitor combinations in cancer patients. The combination of a depolymerizing and a stabilizing agent is a superior anti-tumor treatment. The biological basis of the effect is not understood. Results A single compound containing both colchicine and paclitaxel structures was synthesized. Colchicine is an alkaloid with a trimethoxyphenyl ring (ring A, a ring with an acetamide linkage (ring B, and a tropolone ring (ring C. Although rings A and C are important for tubulin-binding activity, the acetamide linkage on ring B could be replaced by an amide containing a glutamate linker. Alteration of the C-7 site on paclitaxel similarly had little or no inhibitory effect on its biological activity. The linker was attached to this position. The coupled compound, colchitaxel (1, had some of the same effects on microtubules as the combination of starting compounds. It also caused shortening and fragmentation of the + end protein cap. Conclusion Since microtubule inhibitor combinations give results unlike those obtained with either inhibitor alone, it is important to determine how such combinations affect cell shape and growth. Colchitaxel shows a subset of the effects of the inhibitor combination. Thus, it may be able

  10. Binding of dihydroxynaphthyl aryl ketones to tubulin colchicine site inhibits microtubule assembly.

    Science.gov (United States)

    Gutierrez, Eunices; Benites, Julio; Valderrama, Jaime A; Calderon, Pedro Buc; Verrax, Julien; Nova, Esteban; Villanelo, Felipe; Maturana, Daniel; Escobar, Cristian; Lagos, Rosalba; Monasterio, Octavio

    2015-10-23

    Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed among the assayed compounds seem to be related to the structure and position of the aryl substituent bonded to the carbonyl group. Compounds 2, 3 and 4, which contain a heterocyclic ring, presented higher affinity for tubulin compared to the carbocyclic analogue 5. Compound 4 showed the best affinity of the series, with an IC50 value of 2.1 μM for microtubule polymerization inhibition and a tubulin dissociation constant of 1.0 ± 0.2 μM, as determined by thermophoresis. Compound 4 was more efficacious in disrupting microtubule assembly in vitro than compound 5 although it contains the trimethoxyphenyl ring present in colchicine. Hydrogen bonds with Asn101 of α-tubulin seem to be responsible for the higher affinity of compound 4 respects to the others. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    Science.gov (United States)

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  12. Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design.

    Science.gov (United States)

    Rohena, Cristina C; Telang, Nakul S; Da, Chenxiao; Risinger, April L; Sikorski, James A; Kellogg, Glen E; Gupton, John T; Mooberry, Susan L

    2016-02-01

    A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC(50) values of 10-16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Effect of colchicine on polycystic ovary syndrome: an experimental study.

    Science.gov (United States)

    Gozukara, Ilay Ozturk; Pınar, Neslihan; Ozcan, Oğuzhan; Ozgur, Tumay; Dokuyucu, Recep; Kurt, Raziye Keskin; Kucur, Suna Kabil; Aksoy, Ayşe Nur

    2016-03-01

    To investigate whether there is any therapeutic effect of colchicine on a rat model of polycystic ovary syndrome (PCOS). Twenty-two Wistar-Albino rats were randomly assigned into four with 8 rats in each group: control group; PCOS only group; PCOS-metformin group and PCOS-colchicine group. PCOS was induced by gavage with letrozole once daily at the concentration of 1 mg/kg orally with 21 consecutive days. After PCOS model assessment, PCOS-metformin group was received metformin orally with 500 mg/kg and PCOS-colchicine group was received colchicine orally with 1 mg/kg for the 35 day. Histopathology of ovaries, circulating estrone (E1), estradiol (E2), total testosterone, androstenedione and c-reactive protein (CRP) levels were evaluated. cystic and atretic follicle number was significantly decreased, but CRP and hormone parameters were not significantly changed with colchicine treatment. Colchicine has provided histopathological improvement compared with metformin in PCOS rat model.

  14. Lichenoid drug eruption induced by colchicine: case report.

    Science.gov (United States)

    An, Isa; Demir, Vasfiye; Akdeniz, Sedat

    2017-06-01

    Lichenoid drug eruption (LDE) is a common cutaneous side effect of drugs including antimalarials, antihypertensives, nonsteroids, anti-inflammatory drugs and diuretics. The physiopathologic relationship between colchicine treatment and LDE is unclear. There is very little documentation of LDE induced by colchicine in the literature. In this report, we present a case that developed LDE on the abdomen and the legs during the colchicine treatment.

  15. Colchicine concentration in leukocytes of patients with familial Mediterranean fever.

    OpenAIRE

    Chappey, O; Niel, E; Dervichian, M; Wautier, J L; Scherrmann, J M; Cattan, D

    1994-01-01

    Free and total plasma, granulocyte and mononuclear cell colchicine concentrations were measured by radioimmunoassay in 30 patients with familial Mediterranean fever treated with colchicine 0.5 to 2 mg day-1. Colchicine concentrations showed a large intersubject variability in plasma (0.13-1.75 ng ml-1), granulocytes (4 to 64 ng/10(9) cells), and mononuclear cells (11.4 to 57.6 ng/10(9) cells). Whereas unbound and total plasma colchicine concentrations were well correlated, no correlation was ...

  16. Colchicine for children with pericarditis: systematic review of clinical studies.

    Science.gov (United States)

    Alabed, Samer; Pérez-Gaxiola, Giordano; Burls, Amanda

    2016-10-01

    To review the evidence for the efficacy and safety of colchicine in children with pericarditis. Systematic review. The following databases were searched for studies about colchicine in children with pericarditis (June 2015): Cochrane Central, Medline, EMBASE and LILACS. All observational and experimental studies on humans with any length of follow-up and no limitations on language or publication status were included. The outcomes studied were recurrences of pericarditis and adverse events. Two authors extracted data and assessed quality of included studies using the Cochrane risk of bias tool for non-randomised trials. Two case series and nine case reports reported the use of colchicine in a total of 86 children with pericarditis. Five articles including 74 paediatric patients were in favour of colchicine in preventing further pericarditis recurrences. Six studies including 12 patients showed that colchicine did not prevent recurrences of pericarditis. No randomised controlled trials (RCTs) were found. Although colchicine is an established treatment for pericarditis in adults, it is not routinely used in children. There is not enough evidence to support or discourage the use of colchicine in children with pericarditis. Further research in the form of large double-blind RCTs is needed to establish the efficacy of colchicine in children with pericarditis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Preliminary study on the inducement effect of colchicine during ...

    African Journals Online (AJOL)

    Administrator

    2011-06-20

    Jun 20, 2011 ... Key words: Ginkgo biloba L., microsporogenesis, colchicine, 2n pollen, high performance liquid chromatography ... HPLC,. High performance liquid chromatography. medical application (Du and Zhao, 2003; Andreas et al.,. 1992; Brunetti et al., 2006; DeKosky et al., 2008). ...... Fatal colchicine toxicity. Med.

  18. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert

    2003-01-01

    The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3...

  19. Effect of Colchicine Induced Mutagenesis on Growth and Yield of ...

    African Journals Online (AJOL)

    Chemical mutagenesis through the use of colchicine on the seeds of two varieties of sesame (Sesamum indicum L. Var. Ex-Sudan and E-8) with the aim of inducing variability that could be exploited in the genetic improvement of its growth and yield was carried out. The sesame seeds were treated with colchicines at four ...

  20. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert

    2003-01-01

    The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3...... weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated...... the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice...

  1. Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.

    Science.gov (United States)

    Peake, Philip W; Pianta, Timothy J; Succar, Lena; Fernando, Mangalee; Buckley, Nicholas A; Endre, Zoltan H

    2015-06-01

    Colchicine is an anti-inflammatory alkaloid used for the treatment of acute gout, but has a narrow therapeutic index. Colchicine overdoses are relatively rare, but have high mortality requiring rapid treatment. To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab(™)) to protect rats against renal and other injury 24 h after colchicine ingestion. Rats were gavaged with colchicine (5 mg/kg), then 2 h later injected intraperitoneally with 5 ml of sterile saline, or Fab anti-colchicine, a newly available ovine antibody to colchicine. Samples of blood were taken at 1, 2, 5 and 24 h after gavage, and urine was collected from 5 to 24 h after gavage. Concentrations of colchicine in tissue, blood and urine were measured by liquid chromatography/mass spectrometry, concentrations of Fab anti-colchicine, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 or KIM-1 by enzyme-linked immunosorbent assay or ELISA, while concentrations of creatine kinase and creatinine (Cr) were measured enzymatically. Colchicine equilibrated rapidly throughout the body and increased serum creatine kinase. Fab anti-colchicine also rapidly redistributed to the blood and remained at high concentrations over 24 h. Fab anti-colchicine caused a rapid 7.1-fold increase in serum colchicine level, followed by excretion of both colchicine and Fab anti-colchicine through the urine. This was associated with the accumulation of colchicine in the kidney, a reversal of colchicine-induced diarrhoea, and increasing urinary NGAL level; from 168 ± 48 to 477 ± 255 ng/mmol Cr [mean ± standard deviation or SD]. Fab anti-colchicine greatly increased the clearance of colchicine, although increasing NGAL level suggested the presence of mild kidney damage. These data suggest clinical utility for Fab anti-colchicine in the treatment of colchicine overdose.

  2. Different duration of Colchicine for preventing recurrence of Gouty arthritis

    Directory of Open Access Journals (Sweden)

    H Karimzadeh

    2006-05-01

    Full Text Available Background: Gout is a Common recurrent clinical syndrome characterized by increased serum uric acid and recurrent attacks of acute arthritis. Colchicine is used for Prophylaxis against recurrence of arthritis, but the duration of its administration has mentioned variable. In this study, optimal duration of prophylactic colchicine for prevention of gouty arthritis was assessed. Methods : In a clinical trial 190 patients with gouty arthritis divided randomly to group 1,2and 3 and received colchicine for 3 to 6, 7 to 9 and 10 to 12 months then colchicine discontinued and the patients followed one year for recurrence of arthritis. Result assessed by survival analysis with Kaplan –Meier method. Results: The probability of recurrence of arthritis (in order of duration of colchicine prophylaxis was 54%, 27.5% and 23%, respectively. The difference between group one and others was statistically significant, but between group 2 and 3 was not statistically significant. Conclusion: The most suitable duration of colchicine prophylaxis that accompanied with lower recurrence rate was 7-9 months, which seems more cost -effective than 10-12 months regimen. Key words: Gout, Colchicine, Arthritis, Recurrence

  3. Colchicine --- update on mechanisms of action and therapeutic uses

    Science.gov (United States)

    Leung, Ying Ying; Hui, Laura Li Yao; Kraus, Virginia B

    2015-01-01

    Objectives To review the literature and provide an updates on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. Methods We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. Results The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and Familial Mediterranean Fever, to osteoarthritis, pericarditis and atherosclerosis. Conclusion Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions. PMID:26228647

  4. Colchicine--Update on mechanisms of action and therapeutic uses.

    Science.gov (United States)

    Leung, Ying Ying; Yao Hui, Laura Li; Kraus, Virginia B

    2015-12-01

    To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Formulation of colchicine ointment for the treatment of acute gout.

    Science.gov (United States)

    Maduri, Sairam; Atla, Venkateshwar Reddy

    2012-11-01

    In spite of being the fastest acting drug available for the control of an acute gout attack, colchicine is generally considered a last alternative in gout therapy. This is mainly due to the severe adverse effects associated with its administration through the enteral and parenteral routes, as well as its high risk/benefit ratio. The preparation of dosage forms of colchicine that can be administered by alternative routes is therefore a beneficial exercise. Among the formulable substitute dosage forms of colchicine, its ointment seems to be the best option available due to its ability to deliver the drug transdermally as well as its ease of preparation and evaluation. In this study, we prepared and tested 0.2% and 0.5% colchicine ointments for their effectiveness in delivering colchicine transdermally. Colchicine ointment was prepared using a self-formulated water-in-oil type of emulsion ointment base, with the colchicine dissolved in the water portion of the ointment base. In vitro drug release studies were carried out using the Franz diffusion test apparatus and an ultraviolet (UV)-visible spectrophotometer was used to quantify the drug in the samples. Rabbits were used as test animals for in vivo studies and the blood samples were analysed using the UV-visible spectrophotometer. Colchicine was found to be well-absorbed transdermally, although absorption was not 100%. No side effects were associated with its 0.2% formulation. Ointments containing colchicine in low concentrations may be a feasible and effective treatment option for the prevention and treatment of acute gout attacks.

  6. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

    Science.gov (United States)

    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  7. Colchicine in cardiovascular disease: an ancient drug with modern tricks.

    Science.gov (United States)

    Tong, David C; Wilson, Andrew M; Layland, Jamie

    2016-07-01

    From the dark history of being a poison and purgative, colchicine has risen to become one of the few irrefutable positives in the history of pharmacology in the management of myriad inflammatory conditions. Colchicine exerts its action through binding to tubulin, which in turn affects several cellular processes and pathways modulating the inflammatory response. Despite narrow therapeutic-toxicity window and the most common complaint of gastrointestinal upset, its list of medicinal use is expanding in recent years as we continue to unravel the mystery of this ancient remedy. In this review, we summarise the history of colchicine use, discuss its pharmacokinetics and mechanism of actions, and examine the most up-to-date evidence of colchicine in the treatment of various cardiac conditions with a focus on cardiovascular disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. LC-MS/MS quantification of free and Fab-bound colchicine in plasma, urine and organs following colchicine administration and colchicine-specific Fab fragments treatment in Göttingen minipigs.

    Science.gov (United States)

    Fabresse, Nicolas; Allard, Julien; Sardaby, Marine; Thompson, Adrian; Clutton, R Eddie; Eddleston, Michael; Alvarez, Jean-Claude

    2017-08-15

    Clinical evaluation of a colchicine specific antigen-binding fragment (Fab) in order to treat colchicine poisoning required the development of an accurate method allowing quantification of free and Fab-bound colchicine in plasma and urine, and free colchicine in tissues, to measure colchicine redistribution after Fab administration. Three methods have been developed for this purpose, and validated in plasma, urine and liver: total colchicine was determined after denaturation of Fab by dilution in water and heating; free colchicine was separated from Fab-bound colchicine by filtration with 30KDa micro-filters; tissues were homogenized in a tissue mixer. Deuterated colchicine was used as internal standard. Samples were extracted by liquid-liquid extraction and analyzed with a LC-MS/MS. LOQ were 0.5ng/mL in plasma and urine for free and total colchicine and 5pg/mg in tissues. The methods were linear in the 0.5-100ng/mL range in plasma and urine, and 5-300pg/mg in tissues with determination coefficients>0.99. Precision and accuracy of QC samples presented a CVcolchicine and treated with colchicine specific Fab fragments. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Leukopenia associated with long-term colchicine administration.

    Science.gov (United States)

    Beggs, Ashton E; Reeves, David J; Noel, Nancy S

    2012-12-15

    A case of leukopenia in a patient receiving colchicine for calcium pyrophosphate dihydrate deposition disease, or pseudogout, is reported. An 85-year-old man experienced leukopenia likely due to colchicine. His medical history included chronic lymphocytic leukemia (CLL), pseudogout, osteoarthritis, and hypertension. In February 2011, his white blood cell (WBC) count was 2700 cells/μL, and his absolute neutrophil count (ANC) was 2200 cells/μL. Colchicine 0.6 mg orally daily was initiated in March for the prophylaxis of pseudogout. His WBC count decreased, and his colchicine dosage was reduced to 0.6 mg every other day. Despite this decreased dosage, his WBC count and ANC were 600 and 100 cells/μL, respectively, in September. In October, the patient received chemotherapy for presumed worsening of his CLL. One month later, his WBC count and ANC were 400 and 200 cells/μL, respectively. Subcutaneous filgrastim was administered, and colchicine was discontinued. At the end of November, he received another cycle of chemotherapy followed by pegfilgrastim. On the day of pegfilgrastim administration, the patient's WBC count and ANC were 2000 and 1300 cells/μL, respectively. Two weeks later, his WBC count was 8800 cells/μL, and his ANC was 8300 cells/μL. Daily colchicine was restarted at the end of December. Two months later, his WBC count and ANC were 800 and 500 cells/μL, respectively. Given the symptomatic relief with colchicine, therapy was continued with close monitoring. A patient with CLL developed leukopenia in association with colchicine administration for pseudogout.

  10. Colchicine in Renal Medicine: New Virtues of an Ancient Friend.

    Science.gov (United States)

    Solak, Yalcin; Siriopol, Dimitrie; Yildiz, Abdulmecit; Yilmaz, Mahmut Ilker; Ortiz, Alberto; Covic, Adrian; Kanbay, Mehmet

    2017-01-01

    Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function. © 2016 S. Karger AG, Basel.

  11. Colchicine-induced myoneuropathy in a cyclosporine-treated renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Kyungmin Huh

    2013-06-01

    Full Text Available Colchicine is a relatively safe medication that is widely used for both prevention and treatment of gout attack. However, serious adverse events, including myoneuropathy and multiorgan failure, have been reported. We report a case of colchicine-induced myoneuropathy in a female kidney transplant recipient who had been taking cyclosporine. She developed gastrointestinal discomfort and paresthesia 5 days after the initiation of colchicine. She showed signs of myoneuropathy, and hepatic and renal injury. Colchicine toxicity was suspected, and colchicine was discontinued. Her symptoms and laboratory findings improved gradually. Literature was reviewed for previous reports of colchicine-induced myoneuropathy in solid organ transplant recipients.

  12. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-01-01

    Abstract Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  13. Hemophagocytic lymphohistiocytosis and Pelger-Huët anomaly associated with colchicine intoxication

    Directory of Open Access Journals (Sweden)

    Baris Malbora

    2014-06-01

    Full Text Available Colchicine is frequently used in the treatment of familial Mediterranean fever (FMF. First symptoms of colchicine intoxication are gastrointestinal disturbances, such as abdominal cramps, diarrhea, pancytopenia and so on. Herein, we report a female FMF patient with pancytopenia and hemophagocytic lymphohitiocytosis (HLH, following colchicine intoxication for committing suicide. To our knowledge, this is the first reported case of a patient with HLH associated with colchicine intoxication.

  14. Colchicine toxicity in renal patients - Are we paying attention?

    Science.gov (United States)

    Medani, Samar; Wall, Catherine

    2016-08-01

    Colchicine is an approved agent in the management and prophylaxis of gout and familial Mediterranean fever but its therapeutic value is limited by its narrow therapeutic index. Multisystem toxicity is uncommonly reported; and is often associated with renal impairment and/or specific drug interactions. We report two cases of colchicine toxicity marked by severe neuromyopathy in a diabetic with stage 4 chronic kidney disease (CKD) and a renal transplant recipient. Both patients presented with diarrhea, acute on chronic kidney injury and progressive muscle weakness while on colchicine for several weeks or longer. In addition to kidney disease, risk factors for colchicine toxicity included maintenance therapy with simvastatin in the first patient and cyclosporine in the second. Creatine phosphokinase (CPK) was elevated in both cases at presentation and neurophysiologic studies showed a pattern of severe myopathy with axonal sensorimotor neuropathy. The first patient recovered from neurological weakness in a few weeks, but the second patient suffered an extraordinarily protracted and severe neuromuscular disability for a year. The two cases reinforce the need for extra vigilance in prescribing and monitoring colchicine therapy in renal patients with specific attention to drug interactions known to increase the risk of toxicity, thus avoiding such combinations in patients with renal impairment.

  15. Diploidization of cucumber (Cucumis sativus L. haploids by colchicine treatment

    Directory of Open Access Journals (Sweden)

    Vesselina Nikolova

    2014-01-01

    Full Text Available Haploid cucumber plants are totally infertile and do not undergo spontaneous diploidization. The use of haploids depends on the possibility of doubling the chromosome number and the obtaining of stable doubled haploids (DH. Four haploids of different genotypes propagated vegetatively were treated with colchicine in order to obtain DH. The following procedures were used: 1 apical shoot meristem treatment, 2 soaking of shoot explants, 3 placing of shoot explants on medium with colchicine. Plants of the C1 generation were evaluated in respect to morphological and cytological characters and fertility. The best result of 20.9% DH was obtained after repeated treatment of the meristem with colchicine. A large group of chimeras (28.5% was also distinguished as were haploids and tetraploids. DH plants were fertile and gave uniform progeny. Chimeras had a decreased fertility and showed disturbances in meiotic divisions.

  16. Cochrane Corner: Colchicine in acute and recurrent pericarditis.

    Science.gov (United States)

    Caldeira, Daniel; Vaz-Carneiro, António; Costa, João

    2015-11-01

    The potential anti-inflammatory effect of colchicine has been explored in many conditions, including pericarditis. The Cochrane Collaboration Systematic Review included four randomized controlled trials enrolling 564 patients with acute pericarditis (two studies) or recurrent pericarditis (two studies), followed for a period of 20-24 months. Colchicine was associated with a significant reduction in short-term persistence of chest pain and in long-term risk of recurrence of pericarditis. No significant increase in overall adverse events was observed. Despite the available evidence, the use of colchicine in this context remains strictly off-label. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  17. Colchicine aggravates coxsackievirus B3 infection in mice.

    Science.gov (United States)

    Smilde, Bernard J; Woudstra, Linde; Fong Hing, Gene; Wouters, Diana; Zeerleder, Sacha; Murk, Jean-Luc; van Ham, Marieke; Heymans, Stephane; Juffermans, Lynda J M; van Rossum, Albert C; Niessen, Hans W M; Krijnen, Paul A J; Emmens, Reindert W

    2016-08-01

    There is a clinical need for immunosuppressive therapy that can treat myocarditis patients in the presence of an active viral infection. In this study we therefore investigated the effects of colchicine, an immunosuppressive drug which has been used successfully as treatment for pericarditis patients, in a mouse model of coxsackievirus B3(CVB3)-induced myocarditis. Four groups of C3H mice were included: control mice (n=8), mice infected with CVB3 (1×10(5) PFU, n=10), mice with colchicine administration (2mg/kg i.p, n=5) and mice with combined CVB3 infection and colchicine administration (n=10). After three days, the heart, pancreas and spleen were harvested and evaluated using (immuno)histochemical analysis and CVB3 qPCR. Mice were terminated at day 3 post-virus infection as colchicine treatment rapidly resulted in severe illness and mortality in CVB3-infected mice. Colchicine significantly decreased the number of macrophages in the heart in CVB3-infected mice (pcolchicine caused complete destruction of the acini in the CVB3-infected mice and also significantly decreased macrophage (pcolchicine treatment of CVB3-infected mice induced massive apoptosis in the white pulp and significantly inhibited the virus-induced increase of megakaryocytes in the spleen (pcolchicine significantly increased CVB3 levels in both the pancreas and the heart. Colchicine treatment in CVB3-induced myocarditis has a detrimental effect as it causes complete destruction of the exocrine pancreas and enhances viral load in both heart and pancreas. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Optimization of 4-(N-Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site

    Science.gov (United States)

    2015-01-01

    The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a–c and 5a–m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI50 1.9–3.2 nM), significant potency against tubulin assembly (IC50 0.77 μM), and substantial inhibition of colchicine binding (99% at 5 μM). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose. PMID:24502232

  19. Polyploid induction of Allium ascalonicum L. by colchicine

    Directory of Open Access Journals (Sweden)

    SUMINAH

    2002-01-01

    Full Text Available The low production rate of shallot (Allium ascalonicum L. in Indonesia could be caused by rarely excellent cultivars. Colchicine was one of the mutation agents frequently used in plant breeding in order to get polyploidy of cultivars. The aim of this research was to find out the differentiation of morphometric evidences and ploidy of shallot chromosomes induced by colchicines 1%. Preparation was made by squash method and stained by acetocarmine. The results indicated that the amount, length and shape of chromosomes altered by the application of the agent. The polyploids produced could be grouped into tetraploids, pentaploids, hexaploids, octaploids, and nonaploids.

  20. Colchicine intoxication: a report of two suicide cases

    Directory of Open Access Journals (Sweden)

    Erden A

    2013-12-01

    Full Text Available Abdulsamet Erden,1 Hatice Karagoz,1 Hasan Hüseyin Gümüscü,1 Samet Karahan,1 Mustafa Basak,1 Fatma Aykas,1 Kadir Bulut,1 Ali Cetinkaya,1 Deniz Avci,1 Orhan Kürsat Poyrazoglu2 1Internal Medicine Department, 2Gastroenterology Department, Kayseri Training and Research Hospital, Kayseri, Turkey Abstract: Colchicine, an old and well-known drug, is an alkaloid extracted from Colchicum autumnale and related species. Colchicine inhibits the deposition of uric acid crystals and is an inhibitor of mitosis. Nausea, vomiting, abdominal pain, and diarrhea, with a massive loss of fluid and electrolytes are the first clinical symptoms of colchicine poisoning. Stomach lavage and rapid gastric decontamination with activated charcoal are crucial. An acute dose of about 0.8 mg/kg of colchicine is presumed to be fatal. We report the clinical outcomes of two different cases of colchicine intoxication for attempted suicide. The dose required for morbidity or mortality varies significantly. The dose of 1 mg/kg in the first case was directly related with mortality, while the dose of 0.2 mg/kg in the second was related with survival. The other difference between the patients was the time of arrival to hospital after ingestion. This period was 4 hours for case 1 and only 1, hour for case 2. The initiation of treatment later than 2 hours after ingestion of colchicine may significantly impair treatment because the absorption time for colchicine after oral administration is about 30–120 minutes. The rising lactate level and high anion gap metabolic acidosis in our patient (case 1 were attributed to lactic acidosis, so hemodialysis was performed, and the duration of hemodialysis was prolonged. Lactic acidosis in the first case was one of the reasons for mortality. The most important parameters which define the chance of survival are the dose of ingested drugs and the arrival time to hospital after ingestion. The patients must be monitored closely for lactic acidosis

  1. Colchicine-Induced Tetraploidy and Changes in Allele Frequencies in Colchicine-Treated Populations of Diploids Assessed with RAPD Markers in Gossypium arboreum L.

    OpenAIRE

    RAUF, Saeed; KHAN, Iftikhar Ahmad; KHAN, Farooq Ahmad

    2006-01-01

    Two cultivars of cotton G. arboreum L. cv. FDH-228 and HK-113 were treated with colchicine solution (1%) with 3 methods of application. Colchicine application at the seedling stage on shoot apex was successful. Tetraploid plants of arboreum (4x = 2n = 52) had larger vegetative, reproductive parts, but less frequent stomata and higher optical density of DNA than their normal diploid counterparts (2n = 26). Results also showed that individuals that escaped the duplicating effects of colchicine ...

  2. Photoaffinity studies of the tubulin-colchicine binding site

    International Nuclear Information System (INIS)

    Hahn, K.M.

    1987-01-01

    A variety of colchicine derivatives were synthesized and coupled with 3,3,3-trifluoro-2-diazapropionyl chloride (TFDP-Cl) to produce colchicine photoaffinity analogs for use in tubulin labelling studies. Photoaffinity analogs of allocolchicine and podophylotoxin were also made using the same photoreactive moiety. Several labels were found to be effective inhibitors of tubulin polymerization. The approximate tubulin binding constants of the labels, calculated from polymerization inhibition data, varied between 2.2 x 10 5 to 2.5 x 10 3 M -1 . The labels chosen for use in tubulin labelling experiments were (N-TFDP) deacetyl-thiocolchicine 1, (O-TFDP)thiocolchifoline 2, and (O-TFDP)-2-demethylthiocolchicine 3. Compound 1 was found to bind tubulin reversibly and to competitively inhibit colchicine binding. Methods for the incorporation of tritium and 14 C in these labels were developed. Conditions were found which caused labels to insert into solvent without photorearrangement of the colchicine skeleton. Catalytic base caused the α-diazo amide of 1 to rearrange to a triazole

  3. Effect of water stress on growth of colchicine induced polyploid ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-10-20

    Oct 20, 2008 ... Compared with normal diploid plants, the polyploid plants of C. palmata and L. sphaerica inducted in our experiments had short stems. ... Jacobs, 2002) and roots of C. palmata are also edible. (Fox and Norwood Young, 1982; ..... colchicine-treated seedlings by rural farmers will ensure availability of leafy ...

  4. Colchicine aggravates coxsackievirus B3 infection in mice

    NARCIS (Netherlands)

    Smilde, Bernard J.; Woudstra, Linde; Fong Hing, Gene; Wouters, Diana; Zeerleder, Sacha; Murk, Jean-Luc; van Ham, Marieke; Heymans, Stephane; Juffermans, Lynda J. M.; van Rossum, Albert C.; Niessen, Hans W. M.; Krijnen, Paul A. J.; Emmens, Reindert W.

    2016-01-01

    There is a clinical need for immunosuppressive therapy that can treat myocarditis patients in the presence of an active viral infection. In this study we therefore investigated the effects of colchicine, an immunosuppressive drug which has been used successfully as treatment for pericarditis

  5. RAPD analysis of colchicine induced variation of the Dendrobium ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... RAPD analysis of colchicine induced variation of the. Dendrobium Serdang beauty. Khosravi, A. R.1, Kadir, M. A.1, Kadzemin, S. B.2, Zaman, F. Q.3 and De Silva, A. E.4. 1Department of Agrotechnology, Faculty Agriculture, University Putra Malaysia. 2Department of Crop Science, Faculty Agriculture, ...

  6. Genetic variation in colchicine-treated regenerated plants of ...

    Indian Academy of Sciences (India)

    to detect the number of chromosome and to evaluate the ap- plicability of RAPD markers to assess genetic variability in regenerated plants of E. globulus treated by colchicine. *For correspondence. E-mail: zhanghanyao@hotmail.com. Materials and methods. Plant materials. Tissue culture of E. globulus was performed as ...

  7. RAPD analysis of colchicine induced variation of the Dendrobium ...

    African Journals Online (AJOL)

    Variation was detected in Dendrobium Serdang Beauty V (DSB V) plantlets regenerated from protocorm like bodies (plbs) induced by various concentration levels of colchicines in the Murashige and Skoog media (MS) supplemented with 1.5 mg/L IBA. RAPD analysis detected 6 - 26% variation in the regenerants from the ...

  8. Colchicine resistant FMF is not always true resistance

    African Journals Online (AJOL)

    Tawhida Y. Abdel Ghaffar

    Colchicine;. Familial Mediterranean fever. Abstract Crohn's disease and familial Mediterranean fever are both inflammatory diseases char- ... the same chronic relapsing behavior, infil- tration by neutrophils at the site of injury, and abnormal ... moglobin was 9.6 g/dl); white blood cells and platelets were within normal ranges.

  9. Colchicine and amiprophos-methyl (APM) in polyploidy induction in ...

    African Journals Online (AJOL)

    The objective was to assess the colchicine and amiprophos-methyl (APM) concentration and exposure period in the chromosome duplication of breed banana plants diploids. Banana stem tips were used from the following genotypes: breed diploids (1304-04 [Malaccensis x Madang (Musa acuminata spp. banksii)] and ...

  10. Colchicine and amiprophos-methyl (APM) in polyploidy induction in ...

    African Journals Online (AJOL)

    Jane

    2011-10-12

    Oct 12, 2011 ... presented 25% tetraploid plants and in the 8694-15 genotype, the 5.0 mM concentration for 48 h ... dynamic in plant cells (Morejohn and Fosket, 1984) and .... colchicine and APM (amiprophos-methyl) in different exposure periods, after sixty days in vitro. Antimitotic Concentration. Survival (%). Death (%).

  11. Effect of colchicine on mitotic polyploidization and morphological ...

    African Journals Online (AJOL)

    Ajai

    2012-05-15

    May 15, 2012 ... The survival rate and germination percentage is severely affected by various treatments of colchicine. In this investigation, doses related effects of the ploidy treatments on quantitative traits were noticed. Result indicates reduction in plant height, number of leaves per branch, but increase in number of.

  12. Comparison of in vivo and in vitro Colchicine Application for ...

    African Journals Online (AJOL)

    This study was performed to compare the efficiency of different colchicine application methods for doubling of haploid melon plants in melon breeding programs. Doubled haploids assist breeding by reducing time for the recovery of homozygous breeding lines. Irradiated pollen technique provides successful results in ...

  13. Colchicine attenuates renal fibrosis in a murine unilateral ureteral obstruction model.

    Science.gov (United States)

    Itano, Seiji; Satoh, Minoru; Kadoya, Hiroyuki; Sogawa, Yuji; Uchida, Atsushi; Sasaki, Tamaki; Kashihara, Naoki

    2017-06-01

    The present study aimed to assess the effects of colchicine, a known anti‑inflammatory agent, on renal fibrosis using a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6 mice were divided into two groups, vehicle‑ and colchicine‑treated. Colchicine (0.5 mg/kg/day) was administered by osmotic pump, and the UUO procedure was performed on the left kidney 7 days later. The mice were sacrificed at 14 days following UUO. Colchicine treatment suppressed interstitial fibrosis of the UUO kidneys. In addition, fibrogenic gene expression in the UUO kidneys was decreased by colchicine administration. NRK‑49F normal rat kidney fibroblasts were cultured with or without colchicine under angiotensin II stimulation, following which a wound‑healing assay and actin fiber staining were performed to evaluate the effects of colchicine in vitro. Colchicine was demonstrated to inhibit angiotensin II‑induced fibroblast migration in vitro in a concentration‑dependent manner. Colchicine treatment also suppressed the angiotensin II‑induced activation of Ras homolog gene family member A in NRK‑49F cells. In conclusion, colchicine treatment significantly inhibited fibroblast activity in vitro and attenuated renal fibrosis in vivo in UUO‑operated mice. Therefore, the prevention of renal fibrosis following injury may represent a novel therapeutic application for colchicine.

  14. Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines.

    Science.gov (United States)

    Lin, Zu-Yau; Kuo, Chao-Hung; Wu, Deng-Chyang; Chuang, Wan-Long

    2016-02-01

    Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c-nu) experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer. Copyright © 2016. Published by Elsevier Taiwan.

  15. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma.

    Science.gov (United States)

    Wu, Chun-Chieh; Lin, Zu-Yau; Kuoc, Chao-Hung; Chuang, Wan-Long

    2015-05-01

    Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167). The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015). In addition to the well-known direct colchicine-tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience. Copyright © 2015. Published by Elsevier Taiwan.

  16. Efficacy of colchicine in a child with relapsing bullous Henoch-Schönlein purpura.

    Science.gov (United States)

    Allali, Slimane; Fraitag, Sylvie; Terrier, Benjamin; Bodemer, Christine; Chalumeau, Martin

    2016-01-01

    Colchicine is not usually considered a treatment option for cutaneous lesions of Henoch-Schönlein purpura (HSP) in children. We report a case of pediatric HSP with severe chronic and relapsing cutaneous manifestations that were resistant to corticosteroids. Colchicine had remarkable therapeutic efficacy, with positive dechallenge and rechallenge, without any adverse effects. Colchicine should be considered for chronic, severe cutaneous lesions of pediatric HSP. Colchicine is not usually considered a treatment option for cutaneous lesions of Henoch-Schönlein purpura (HSP) in children. What is New: We report a case of pediatric HSP with severe cutaneous manifestations that responded well to colchicine. Colchicine should be considered for chronic cutaneous lesions of HSP in children.

  17. Three-dimensional organization of micronuclei induced by colchicine in PtK sub 1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Geraud, G.; Laquerriere, F.; Masson, C.; Arnoult, J.; Labidi, B.; Hernandez-Verdun, D. (Univ. Pierre et Marie Curie, Paris (France))

    1989-03-01

    In PtK{sub 1} cells micronucleated by colchicine, the authors previously demonstrated that some micronuclei contain a single chromosome. Here, they investigated interphase chromosome organization in micronucleated PtK{sub 1} cells using conventional electron microscopy and three-dimensional computer reconstruction. The distribution of micronuclei was not always polarized, but in some cells they formed a ring. When this occurred, centrioles and Golgi apparatus were located inside the ring. On freeze-fracture replicas, they observed that nuclear pore distinction among the micronuclei was heterogeneous, and on thin sections some micronuclei displayed an incomplete nuclear envelope, with gaps in the double membrane and areas without lamina or condensed chromatin. By autoradiography, they showed that the fibrillar dots were not sites of active transcription. They applied three dimensional reconstruction to one micronucleated cell containing 22 micronuclei whose size indicated that each micronucleus probably contained one chromosome. In this cell they demonstrated that only the smallest micronuclei had an incomplete nuclear envelope. The presence in micronuclei of either nucleoli or fibrillar dots was found to be mutually exclusive. Taken together, these findings indicate that in the diploid nuclei of PtK{sub 1} cells, the three-dimensional organization of the nucleolar domain seems to be directly controlled by the X-chromosome.

  18. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  19. Novel Colchicine Derivatives and their Anti-cancer Activity.

    Science.gov (United States)

    Johnson, Lorelei; Goping, Ing Swie; Rieger, Aja; Mane, Jonathan Y; Huzil, Torin; Banerjee, Asok; Luduena, Richard; Hassani, Bashar; Winter, Philip; Tuszynski, Jack A

    2017-01-01

    In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays are summarized as well as some animal tests conducted on these compounds. It is concluded that an untapped potential exists for exploiting the colchicine scaffold as a pharmacophore with the possibility of increasing its affinity for tubulin isotypes overexpressed in cancer and decreasing it for normal cells thereby widening the therapeutic window. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Radiolabelling of n- and i-colchicines with positron emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Kothari, P.J.; Cai, S.; Finn, R.D. [Memorial Sloan Kettering Cancer Center, NY (United States)] [and others

    1995-05-01

    Colchicine, a naturally occurring alkaloid and a potent inhibitor of cellular mitosis, is a member of the multi-drug resistance family of drugs. As a potential indicator of multi-drug resistance, the C-10 methoxy group of n-colchicine and C-9 methoxy group of i-colchicine have been radiolabelled. The syntheses of {sup 11}C-labelled n- and i-colchicines have been achieved by allowing desmethyl colchicine to react with {sup 11}C-iodomethane. The isomeric colchicines were purified and isolated by reversed phase HPLC in greater than 90% radiochemical and chemical purity. Using {sup 13}C-iodomethane, {sup 13}C-labelled n- and i-colchicines have also been synthesized for their evaluation at magnetic resonance imaging (MRI) agents. The restrictions imposed by short half-life of the carbon-11 compound prompted our investigation into the syntheses of fluorine-18 labelled colchicine analogues. The nucleophilic displacement of trifluoromthanesulfonate by {sup 18}F-anion yielded a mixture of {sup 18}F-labelled desmethoxy colchicines. The data suggest that the isolation of fluorine-18 analogue is possible and the compound potentially applicable to multi-drug resistance evaluations.

  1. Safety and efficacy of colchicine therapy in the prevention of recurrent pericarditis.

    Science.gov (United States)

    Eun, Judy; Smith, Andrew

    2014-08-01

    A review of published data on the safety and efficacy of colchicine therapy for primary and secondary prevention of pericarditis is presented. Colchicine has been used effectively as an antiinflammatory agent for gout and has shown promise as a treatment for acute and recurrent pericarditis. Several small studies have indicated that colchicine can decrease pericarditis symptom persistence at 72 hours and pericarditis recurrence rates at 18 months compared with conventional therapy (corticosteroids and aspirin or ibuprofen). A review of pooled data from four prospective randomized trials concluded that colchicine is safe and efficacious for the management of acute and recurrent pericarditis, with the results indicating lower rates of the respective primary and secondary endpoints of recurrent disease and symptom persistence in colchicine-treated patients. A separate meta-analysis of five studies found a reduced risk of pericarditis with colchicine use, suggesting that the drug may have clinical utility in both primary and secondary prevention. The accumulated evidence suggests that treatment with colchicine in the context of pericarditis is safe and well tolerated, with gastrointestinal intolerance being the most common adverse event documented in the clinical trials to date. Based on a review of the literature, prevention of recurrent pericarditis with colchicine can be considered a safe and effective option, though some patients have experienced gastrointestinal intolerance. Due to evidence that corticosteroids may potentially exacerbate the risk of relapse, colchicine may be a safer and preferable option. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  2. Colchicine Use Is Associated with Decreased Prevalence of Myocardial Infarction in Patients with Gout

    Science.gov (United States)

    Crittenden, Daria B.; Lehmann, R. Aaron; Schneck, Laura; Keenan, Robert T.; Shah, Binita; Greenberg, Jeffrey D.; Cronstein, Bruce N.; Sedlis, Steven P.; Pillinger, Michael H.

    2013-01-01

    Objective The ability of antiinflammatory strategies to alter cardiovascular risk has not been rigorously examined. Colchicine is an antiinflammatory agent that affects macrophages, neutrophils, and endothelial cells, all of which are implicated in the pathogenesis of cardiovascular disease. We examined whether colchicine use was associated with a reduced risk of myocardial infarction (MI) in patients with gout. Methods We conducted a retrospective, cross-sectional study of all patients with an International Classification of Diseases, 9th ed, code for gout in the electronic medical record (EMR) of the New York Harbor Healthcare System Veterans Affairs network and ≥ 1 hospital visit between August 2007 and August 2008. Hospital pharmacy data were used to identify patients who had filled at least 1 colchicine prescription versus those who had not. Demographics and CV comorbidities were collected by EMR review. The primary outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and C-reactive protein (CRP) level. Results In total, 1288 gout patients were identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users also had fewer deaths and lower CRP levels, although these did not achieve statistical significance. Colchicine effects persisted when allopurinol users were excluded from the analysis. Conclusion In this hypothesis-generating study, gout patients who took colchicine had a significantly lower prevalence of MI and exhibited trends toward reduced all-cause mortality and lower CRP level versus those who did not take colchicine. PMID:22660810

  3. Evaluation of Packed-Bed Reactor and Continuous Stirred Tank Reactor for the Production of Colchicine Derivatives

    OpenAIRE

    Dubey, Kashyap Kumar; Kumar, Dhirendra; Kumar, Punit; Haque, Shafiul; Jawed, Arshad

    2013-01-01

    Bioconversion of colchicine into its pharmacologically active derivative 3-demethylated colchicine (3-DMC) mediated by P450BM3 enzyme is an economic and promising strategy for the production of this inexpensive and potent anticancer drug. Continuous stirred tank reactor (CSTR) and packed-bed reactor (PBR) of 3 L and 2 L total volumes were compared for the production of 3-demethylated colchicine (3-DMC) a colchicine derivative using Bacillus megaterium MTCC*420 under aerobic conditions. Statis...

  4. Improvement of colchicine oral bioavailability by incorporating eugenol in the nanoemulsion as an oil excipient and enhancer

    Science.gov (United States)

    Shen, Qi; Wang, Ying; Zhang, Yi

    2011-01-01

    The effect of eugenol on colchicine transport across an isolated rat intestinal membrane was studied using an in vitro diffusion chamber system. We found that eugenol increased the absorptive transport of the drug efficiently. The effect of eugenol on intestinal absorption of colchicine in an oral administrative nanoemulsion formulation was also demonstrated in vivo. The colchicine nanoemulsion was prepared with isopropyl myristate, eugenol, Tween80, ethanol and water, and eugenol was used as an oil phase in the formulation; an average particle size of this nanoemulsion was 41.2 ± 7.2 nm. The permeation of colchicine in the nanoemulsion across the intestinal membrane was significantly different from that of the control group (0.2 mM colchicine). Finally, co-administration of eugenol in colchicine nanoemulsion to enhance the colchicine bioavailability was investigated by an oral administration method. After oral administration of colchicine (8 mg/kg) in the form of either the nanoemulsion or in free colchicine solution, the relative bioavailability of nanoemulsion and eugenol–nanoemulsion were enhanced by about 1.6- and 2.1-fold, respectively, compared with free colchicine solution. The procedure indicated that the intestinal absorption of colchicine was enhanced significantly by eugenol in the tested nanoemulsion. All the results suggested that eugenol is an efficient component in an oral administrative formulation for improving the intestinal absorption of colchicine. PMID:21753875

  5. Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin.

    NARCIS (Netherlands)

    Velden, W. van der; Huussen, J.; Laak, H.J. ter; Sevaux, R.G.L. de

    2008-01-01

    Neuromyopathy is a rare side effect of chronic colchicine therapy, most often occurring in patients with chronic renal failure. Drugs interacting with colchicine metabolism through CYP(3)A(4) and P-glycoprotein can accelerate accumulation and toxicity. We describe a case of an interaction between

  6. Colchicine Improves Survival, Left Ventricular Remodeling, and Chronic Cardiac Function After Acute Myocardial Infarction.

    Science.gov (United States)

    Fujisue, Koichiro; Sugamura, Koichi; Kurokawa, Hirofumi; Matsubara, Junichi; Ishii, Masanobu; Izumiya, Yasuhiro; Kaikita, Koichi; Sugiyama, Seigo

    2017-07-25

    Several studies have reported that colchicine attenuated the infarct size and inflammation in acute myocardial infarction (MI). However, the sustained benefit of colchicine administration on survival and cardiac function after MI is unknown. It was hypothesized that the short-term treatment with colchicine could improve survival and cardiac function during the recovery phase of MI.Methods and Results:MI was induced in mice by permanent ligation of the left anterior descending coronary artery. Mice were then orally administered colchicine 0.1 mg/kg/day or vehicle from 1 h to day 7 after MI. Colchicine significantly improved survival rate (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%, Pcolchicine group at 4 weeks after MI. Histological and gene expression analysis revealed colchicine significantly inhibited the infiltration of neutrophils and macrophages, and attenuated the mRNA expression of pro-inflammatory cytokines and NLRP3 inflammasome components in the infarcted myocardium at 24 h after MI. Short-term treatment with colchicine successfully attenuated pro-inflammatory cytokines and NLRP3 inflammasome, and improved cardiac function, heart failure, and survival after MI.

  7. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2000-01-01

    The majority of liver fibrosis and liver cirrhosis cases in the Western World is caused by alcohol and hepatotoxic viruses. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients...

  8. Differential Effects of Colchicine on Cardiac Cell Viability in an in vitro Model Simulating Myocardial Infarction.

    Science.gov (United States)

    Margolis, Gilad; Hertzberg-Bigelman, Einat; Levy, Ran; Ben-Shoshan, Jeremy; Keren, Gad; Entin-Meer, Michal

    2016-01-01

    We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFα or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI. © 2016 S. Karger AG, Basel.

  9. Colchicine reduces restenosis after balloon angioplasty treatment for in-stent restenosis.

    Science.gov (United States)

    Kong, Junying; Deng, Ying; Dong, Qiang; Liu, Wenhua; Lu, Ying

    2015-02-01

    Treatment of coronary in-stent restenosis (ISR) is hampered by a high incidence of recurrent ISR. Colchicine is an old drug with known anti-inflammatory and antiproliferative actions. We evaluated the strategy of colchicine combined with conventional balloon angioplasty for the treatment of ISR. Sixty coronary arteries of 60 mini-pigs underwent oversized bare-metal stent implantation to induce ISR. After 28 days, vessels with ISR (≥50% diameter stenosis) were randomly divided into three groups: control (conventional balloon angioplasty combined with placebo), colchicine (conventional balloon angioplasty combined with colchicine) and drug-eluting balloon (DEB). Restenosis and neointima formation were elevated with angiography and histological and morphometric analysis at 28 days after different interventions. Late lumen loss and percent area stenosis at follow-up were lower in colchicine group compared to control group but were similar to those of DEB group. There was no significant difference in proliferating cell nuclear antigen-positive vascular smooth muscle cells and inflammatory score between the colchicine group and the DEB group. The efficacy of colchicine combined with conventional balloon angioplasty for treatment of ISR was comparable to that of DEB. Treatment of ISR might not require a second stent implantation, and colchicine combined with conventional balloon angioplasty seemed to be another consideration. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  10. The Effect of Colchicine on Mean Platelet Volume in Behcet's Disease.

    Science.gov (United States)

    Ataş, Hatice; Cemil, Bengü Cevirgen; Canpolat, Filiz; Gönül, Müzeyyen

    2015-01-01

    Patients with Behcet's Disease are recognized to be at an increased risk for venous and/or arterial thrombosis. Colchicine reduces the initiation and amplification of inflammation and is believed to suppress secretion of cytokines and chemokines and in vitro platelet aggregation. To evaluate the effect of colchicine on levels of mean platelets volume, platelets, erythrocyte sedimentation rate, and C-reactive protein in patients with Behcet's Disease. Patients with Behcet's Disease were evaluated for mean platelets volume before colchicine therapy (Group 1) and after 6-month from beginning of colchicine treatment (Group 2). Fifty-two subjects were evaluated. The mean age was 38.3 years and the female/male ratio was 28/24=1.16. Laboratory tests were evaluated in Group 1 and Group 2. The median level of mean platelets volume was 9.2±0.8 fl in Group 1 and 8.9±0.9 fl in Group 2. Levels of mean platelets volume was found as significant between Group 1 and 2 (p=0.001). Given the proposed relationship between MPV and platelet activity, MPV may serve as a surrogate essay for Behcet's response to colchicine. Colchicine might suppress platelet function and be used in vascular involvement together with immunosuppressant agents in Behcet's Disease. Further studies in large population are needed to evaluate the role of colchicine in platelet function and the effect of colchicine on thrombosis in BD. © 2015 by the Association of Clinical Scientists, Inc.

  11. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...

  12. 11C-Colchicine distribution in tissues of colchicine -sensitive and -resistant neuroblastoma xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, B.M.; Levchenko, A.; Broussard, E. [Memorial Sloan Kettering Cancer Center, NY (United States)] [and others

    1995-05-01

    Multidrug resistance (MDR), a major obstacle in chemotherapy of cancer is thought to be due to the overexpression of a membrane P-glycoprotein (Pgp). P-glycoprotein acts as an energy activated efflux pump, reducing the effective drug concentrations from the MDR tumors. Our earlier studies using neuroblastoma cell lines BE(2)-C (-sensitive), and BE(2)-C/CHCb (-resistant) to colchicine (CHC), showed that uptake of 3H-CHC as well as 14C-CHC in sensitive tumors was twice as much as in resistant tumors. In view of this finding we synthesized 11C-CHC to study the distribution in xenografted animals, since 11C-CHC can be used a a Positron Emission Tomography (PET) tracer in humans. Two groups of Balb/c nude mice (5 animals each) xenografted with BE(2)-C and BE(2)-C/CHCb cells (10 x 10{sup 6} cells per animal) were injected iv retroorbitally with 200 {mu}Ci/100 {mu}l of 11C-CHC per animal. One hour after injection animals were sacrificed by cervical dislocation and blood, tissues and tumors were excised to determine the amount of radioactivity. 11C-CHC biodistribution compared well with 3H-CHC and 14C-CHC distribution. Tumor uptake in sensitive was 1.21 {plus_minus} 0.84% ID/g compared to 0.76 {plus_minus} 0.43% ID/g in resistant tumors. Tumor to blood ratios is sensitive and resistant tumors were 1.62 {plus_minus} 0.41 and 0.69 {plus_minus}0.30 respectively. 11C-Isocolchicine, a byproduct of 11C-CHC synthesis, on the other hand had only 25% uptake as compared to 11C-CHC in both sensitive and resistant tumors. We interpret these results to mean that 11C-CHC behaves similarly to other forms of CHC as a marker of the MDR phenotype. In the future, we plan to use 11C-CHC for identification of MDR status of tumors in vivo using PET scanning.

  13. Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

    2017-05-31

    Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

  14. Patient awareness, knowledge and use of colchicine: an exploratory qualitative study in the Counties Manukau region, Auckland, New Zealand.

    Science.gov (United States)

    Rebello, Caraliese; Thomson, Maree; Bassett-Clarke, Deborah; Martini, Nataly

    2016-06-01

    INTRODUCTION Treatment of gout, specifically with colchicine, varies globally. Colchicine can be fatal due to its narrow therapeutic index and potential for interactions. In New Zealand, cases of intentional and unintentional colchicine overdose have been documented. AIMS To explore patients' knowledge on the use of gout medicines, and in particular their awareness of the maximum dose of colchicine, the dangers of colchicine overdose, and their opinions on restricting colchicine dispensing. The study also investigates where patients receive gout information. METHODS Thirty people with gout presenting to their regular gout clinic in Auckland currently or previously taking colchicine were invited to participate in a 30-min semi-structured interview. Data were analysed using a general inductive thematic approach. FINDINGS Overall, participants had a lack of knowledge regarding colchicine and used variable doses during an acute gout attack. Participants were unsure of the maximum dose of colchicine and several took more than prescribed. The prophylactic use of colchicine and allopurinol varied from 3 weeks to 15 years. Mixed views were reported on restricting colchicine supply. Most participants received gout information from their general practitioner (GP). CONCLUSION Poor understanding of colchicine contributed to inappropriate use and highlights the need for targeted patient education. Considerable inter-patient variability exists in the use of colchicine for acute gout, suggesting the efficacy of low dose regimens be explored. The length of adjunctive colchicine use, as part of a prophylaxis regimen, needs to be regularly reviewed and tailored to each patient. Further research is required on limiting the amount of colchicine dispensed.

  15. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2009-01-01

    Full Text Available Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o. for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.

  16. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Science.gov (United States)

    Kumar, Anil; Dogra, Samrita; Prakash, Atish

    2009-01-01

    Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage. PMID:20798885

  17. Colchicine in prevention of atrial fibrillation following cardiac surgery: Systematic review and meta-analysis

    Science.gov (United States)

    Trivedi, Chintan; Sadadia, Mihir

    2014-01-01

    Objectives: Inflammation is one of the predictors of atrial fibrillation (AF) following surgical or interventional cardiac procedures. Recent evidence suggests that colchicine may represent a new strategy to prevent AF following cardiac procedures. This study aims to assess the antiinflammatory efficacy of colchicine in prevention of early AF event (EAFE). Materials and Methods: We reviewed all available studies that assessed the effectiveness of colchicine therapy on the occurrence of AF in patients undergoing cardiac procedures. Meta-analysis was performed by random effect inverse variance-weighted method by entering AF events and the total population from each study. Results: After thorough review of the databases, we found three studies comparing colchicine and placebo which had EAFE as the outcome. Of 584 patients, 286 patients were on colchicine and 298 on placebo. All the three studies were randomized. After pooled analysis, colchicine was associated with significant reduction in AF events compared to placebo (odds ratio = 0.44 [0.29, 0.66], P Colchicine may prove beneficial in the prevention of AF following cardiac surgery. Further research is warranted. PMID:25538328

  18. Acute pancreatitis related to therapeutic dosing with colchicine: a case report

    Directory of Open Access Journals (Sweden)

    Ting Joseph

    2007-08-01

    Full Text Available Abstract Background Colchicine is used in the treatment and prophylaxis of gout. It possesses a narrow therapeutic window, frequently resulting in dose-limiting gastrointestinal side-effects such as diarrhoea and emesis. As colchicine is a cellular anti-mitotic agent, the most serious effects include myelosuppression, myoneuropathy and multiple organ failure. This occurs with intentional overdose or with therapeutic dosing in patients with reduced clearance of colchicine due to pre-existing renal or hepatic impairment. Acute pancreatitis has rarely been reported, and only in association with severe colchicine overdose accompanied by multi-organ failure. Case presentation We report a case of acute pancreatitis without other organ toxicity related to recent commencement of colchicine for acute gout, occurring in an elderly male with pre-existing renal impairment. Conclusion 1 Colchicine should be used with care in elderly patients or patients with impaired renal function. 2 Aside from myelosuppression, myoneuropathy and multiple organ failure, colchicine may now be associated with acute pancreatitis even with therapeutic dosing; this has not previously being reported.

  19. Colchicine modulates calcium homeostasis and electrical property of HL-1 cells.

    Science.gov (United States)

    Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Lin, Yung-Kuo; Yeh, Yung-Hsin; Chen, Shih-Ann; Chen, Yi-Jen

    2016-06-01

    Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca(2+) ) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole-cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL-1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine-treated HL-1 cells had a longer action potential duration with smaller intracellular Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) content by 10% and 47%, respectively. Colchicine-treated HL-1 cells showed a smaller L-type Ca(2+) current, reverse mode sodium-calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra-rapid activating outward potassium current and apamin-sensitive small-conductance Ca(2+) -activated potassium current compared with control cells. Colchicine-treated HL-1 cells expressed less SERCA2a, total, Thr17-phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16-phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen-induced action potential duration in HL-1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca(2+) regulation and attenuates the electrical effects of collagen, which may contribute to its anti-AF activity. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Assessment of 17 Pediatric Cases With Colchicine Poisoning in a 2-Year Period.

    Science.gov (United States)

    Alaygut, Demet; Kilic, Suar Caki; Kaya, Ali; Oflaz, Mehmet Burhan; Bolat, Fatih; Cevit, Ömer; Icagasioglu, Fusun Dilara

    2016-03-01

    The aim of the study is to discuss clinical effects, treatments, and outcomes of pediatric colchicine poisoning. This study was designed as an observational case series study. The medical records of children aged between 0 and 18 years, who were hospitalized for colchicine poisoning at the Department of Pediatric Intensive Care Unit, Cumhuriyet University Faculty of Medicine, between January 2010 and January 2012, were retrospectively evaluated. We presented 17 children with colchicine poisoning. The mean (SD, range) age of patients was 71.5 (69.19, 18-204) months. The period to apply to the hospital after taking the medications was 7.3 hours (7.97, 30 minutes-26 hours) on average. The use of colchicine was due to diagnosis of Familial Mediterranean fever (FMF) in the families of 8 patients, diagnosis of Behçet disease in 1 patient's father, diagnosis of Behçet disease in 1 patient herself, and diagnosis of FMF in 6 patients themselves. Thirteen patients had taken colchicine at the dose of less than 0.5 mg/kg known as subtoxic and 1 patient had taken colchicine at the dose of greater than 0.8 mg/kg, and doses taken by 3 patients were not known. Fourteen patients (82.4%) had involuntary drug intake. Fifty percent of them were symptomatic at the moment of application and all had gastrointestinal complaints. All patients were observed in intensive care unit upon first admission and received supportive care. One of patients showed total alopecia, one showed leucocytosis, and another one showed acute abdomen picture. None of the patients showed mortality. Mortality of colchicine toxicity is high and quick assessment is absolutely required. In regions where FMF is common and the use of colchicine is high, clinicians should pay attention to symptoms and findings related to colchicine intoxication and keep them in mind in differential diagnosis.

  1. Structure-cytotoxicity relationships for dietary flavonoids

    DEFF Research Database (Denmark)

    Breinholt, V.; Dragsted, L.O.

    1998-01-01

    The cytotoxicity of a large series of dietary flavonoids was tested in a non-tumorigenic mouse and two human cancer cell lines, using the neutral red dye exclusion assay. All compounds tested exhibited a concentration-dependent cytotoxic action in the employed cell lines. The relative cytotoxicity...... of the flavonoids, however, Tvas found to vary greatly among the different cell Lines. With a few exceptions, the investigated flavonoids were more cytotoxic to the human cancer cell lines, than the mouse cell line. The differences in cytotoxicity were accounted for in part by differences in cellular uptake...... and metabolic capacity among the different cell types. In 3T3 cells fairly consistent structure-cytotoxicity relationships were found. The most cytotoxic structures tested in 3T3 cells were flavonoids with adjacent 3',4' hydroxy groups on the B-ring, such as luteolin, quercetin, myricetin, fisetin, eriodictyol...

  2. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Chun-Chieh Wu

    2015-05-01

    Full Text Available Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment. Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p < 0.0001. Nude mouse (BALB/c-nu experiments showed that the increased tumor volume ratios in colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167. The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015. In addition to the well-known direct colchicine–tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience.

  3. Cytotoxic activity of four Mexican medicinal plants.

    Science.gov (United States)

    Vega-Avila, Elisa; Espejo-Serna, Adolfo; Alarcón-Aguilar, Francisco; Velasco-Lezama, Rodolfo

    2009-01-01

    Ibervillea sonorae Greene, Cucurbita ficifolia Bouché, Tagetes lucida Cav and Justicia spicigera Scheltdd are Mexican native plants used in the treatment of different illnesses. The ethanolic extract of J. spicigera and T. lucida as well as aqueous extracts from I. sonorae, C. ficifolia, T. lucida and J. spicigera were investigated using sulforhodamine B assay. These extracts were assessed using two cell line: T47D (Human Breast cancer) and HeLa (Human cervix cancer). Colchicine was used as the positive control. Data are presented as the dose that inhibited 50% control growth (ED50). All of the assessed extracts were cytotoxic (ED50 < 20 microg/ml) against T47D cell line, meanwhile only the aqueous extract from T. lucida and the ethanolic extract from J. spicigera were cytotoxic to HeLa cell line. Ethanolic extract from J. spicigera presented the best cytotoxic effect. The cytotoxic activity of J. spicigera correlated with one of the popular uses, the treatment of cancer.

  4. Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

    Directory of Open Access Journals (Sweden)

    Richard C Wang

    Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

  5. Synthesis of colchicine and isocolchicine labelled with carbon-11 or carbon-13

    Energy Technology Data Exchange (ETDEWEB)

    Kothari, P.J.; Finn, R.D.; Larson, S.M. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    1995-06-01

    The syntheses of isotopically labelled (-)-10-[{sup 11}C/{sup 13}C]-colchicine and (-)-9-[{sup 11}C/{sup 13}C]-isocolchicine have been achieved from the reaction of (-)desmethylcolchicine with [{sup 11}C/{sup 13}C]-iodomethane. The radiolabelled compounds, (-)-10-[{sup 11}C]-colchicine ({sup 11}C-n-colchicine) and (-)-9-[{sup 11}C]-isocolchicine ({sup 11}C-i-colchicine), were isolated by reversed phase HPLC. The total synthesis time was approximately 60 minutes for both radiolabelled compounds with an average specific activity of 240 mCi/{mu}mol calculated to EOB. Utilizing a similar synthetic strategy, we also reported the synthesis of milligram quantities of the carbon-13 enriched compounds and the magnetic resonance signal assignment for (-)-9-[{sup 13}C] isocolchicine. (Author).

  6. An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

    Science.gov (United States)

    Lu, Yan; Chen, Jianjun; Xiao, Min; Li, Wei

    2013-01-01

    Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs. PMID:22814904

  7. Microbial Catalyzed Regio-Selective Demethylation of Colchicine by Streptomyces griseus ATCC 13273.

    Science.gov (United States)

    Zhang, Chao; Sun, Xian; Xu, Shao Hua; Yu, Bo Yang; Zhang, Jian

    2017-11-01

    Colchicinoids and their derivatives are of great importance in pharmaceutical applications, and colchicine is usually used as the first choice for the treatment of gout. To expand the structural diversities and clinical application of colchicinoids, many attempts have been established for the derivatives with better activity or less toxicity. Herein, in this paper, we report a direct microbial transformation of colchicine into 2-O-demethyl-colchicine (M1) and 3-O-demethl-colchicine (M2) by Streptomyces griseus ATCC 13273. It is noteworthy that when DMF was used as co-solvent, the yield of M1 and M2 could reach up to 51 and 31%, respectively. All the structures of the metabolites were elucidated unambiguously by ESI-MS, 1 H-NMR, 13 C-NMR, and 2D-NMR spectroscopy.

  8. Neuroprotective role of vitamin D3 in colchicine-induced Alzheimerâ ...

    African Journals Online (AJOL)

    Adham R. Mohamed

    2014-06-14

    . Recent ... memory. Colchicine-induced cognitive impairment has been established as an animal model of sporadic dementia of Alzhei- mer's type.4. Oxidative stress, due to .... pH 7.4 to remove any red blood cells and clots.

  9. Association Between Colchicine and Risk of Diabetes Among the Veterans Affairs Population With Gout.

    Science.gov (United States)

    Wang, Liya; Sawhney, Monika; Zhao, Yingnan; Carpio, Gandahari Rosa; Fonseca, Vivian; Shi, Lizheng

    2015-06-01

    This study aimed to determine the association between colchicine use and the incidence of diabetes in a cohort of patients with gout. This is a retrospective study of 27,876 adults with gout identified via the Veterans Integrated Services Network 16 data warehouse. Patients had up to 11 years of follow-up (January 1999 through December 2010). The final study sample consisted of 1046 pairs of 1:1 propensity score-matched patients from the colchicine treated and control cohorts. Time to first diabetes development since the first gout diagnosis was modeled. After the propensity score matching, the 12-month baseline variables (eg, age, sex, race, index year, body mass index, serum uric acid, antigout drug use, and health care use) were comparable between the matched cohorts (P > 0.05 for all). Among the 1046 matched pairs, 234 patients who had taken colchicine and 224 patients who had never taken colchicine developed diabetes; the incidence rates were 38.95 and 39.02 per 1000 patient-years, respectively. In Poisson and Cox proportional hazards regression, the risk of incident diabetes was reduced with increased duration of colchicine use, but the difference was not statistically significant (P > 0.05). In a time-varying Cox proportional hazards model, the hazard ratio for incident diabetes among patients who had taken colchicine was 0.877 (95% CI, 0.662-1.163; P = 0.362) compared with those who had not taken colchicine. This study suggests a possible duration- or dose-related association between colchicine use and reduced risk of diabetes in adults with gout even though the risk reduction was not significant. Further studies are needed to confirm findings from this study. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  10. Protective effect of colchicine on ovarian ischemia-reperfusion injury: an experimental study.

    Science.gov (United States)

    Kurt, Raziye Keskin; Dogan, Ayse Citil; Dogan, Murat; Albayrak, Aynur; Kurt, Sefika Nur; Eren, Furkan; Okyay, Ayse Guler; Karateke, Atilla; Duru, Mehmet; Fadillioglu, Ersin; Delibasi, Tuncay

    2015-05-01

    The aim of the present study is to investigate the efficiency of colchicine in the experimental rat ovarian torsion model in the light of histological and biochemical data. A total of 35 Wistar albino female rats were randomly divided into 5 groups, group 1: (control-sham operated, n = 7); group 2: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion; group 3: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion; group 4: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion and a signal dose of oral 1 mL/kg colchicine; and group 5: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion and 5 days of oral 1 mg/kg colchicine. Histopathologic evaluation was performed by a scoring that assesses congestion, bleeding, edema, and cellular degeneration in the ovarian tissue. Catalase, tissue malondialdehyde (MDA), and protein carbonyl levels were calculated. The histopathologic scores, MDA, and protein carbonyl levels in the control and colchicine groups were significantly lower than groups 2 and 3 (P colchicine groups than in groups 2 and 3 (P colchicine treatment persisted up to 5 days. Our study results revealed that colchicine reduced ovarian ischemia-reperfusion injury in experimental rat ovarian torsion model. As the ovarian detorsion is the first choice of the treatment modality in the early phase, antioxidant and anti-inflammatory treatment modalities like colchicine might be used to reduce ovarian ischemia-reperfusion injury. © The Author(s) 2014.

  11. Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin.

    Science.gov (United States)

    Kwon, Oh Chan; Hong, Seokchan; Ghang, Byeongzu; Kim, Yong-Gil; Lee, Chang-Keun; Yoo, Bin

    2017-05-01

    The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. In gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. Of 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P colchicine dose (HR 20.960; 95% CI, 1.835-239.481; P = .014), and concomitant CYP3A4 inhibitor (HR 12.027; 95% CI, 2.743-52.725; P = .001) were associated with increased risk of myopathy. Concomitant use of statins, however, was not, even after adjusting for confounders (HR 1.123; 95% CI, 0.262-4.814; P = .875; IPTW-adjusted HR 0.321; 95% CI, 0.077-1.345; P = .120). Concomitant use of statin and colchicine was not associated with increased risk of myopathy. Thus, concomitant use of statin with colchicine seems to be safe from myotoxicity in gout patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Colchicine Increases Ventricular Vulnerability in an Experimental Whole-Heart Model.

    Science.gov (United States)

    Frommeyer, Gerrit; Krawczyk, Julius; Dechering, Dirk G; Kochhäuser, Simon; Leitz, Patrick; Fehr, Michael; Eckardt, Lars

    2017-05-01

    The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in two concentrations (1 and 3 μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion. Furthermore, there was no significant increase in dispersion of repolarization. However, colchicine induced a dose-dependent significant decrease of effective refractory period (ERP; 1 μM: -19 ms, 3 μM: -22 ms; p colchicine in isolated rabbit hearts resulted in a reduction of ERP in the presence of a stable myocardial repolarization. This led to a significantly elevated inducibility of ventricular fibrillation. In 4 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a pro-arrhythmic or toxic effect of colchicine and underline that further clinical studies on potential adverse effects should be conducted before the drug can be recommended for routine use after atrial fibrillation ablation. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  13. Colchicine in addition to conventional therapy for pericarditis recurrence : An update meta-analysis.

    Science.gov (United States)

    Li, Y-L; Qiao, S-B; Wang, J-Y; Chen, Y-M; Luo, J; Zhang, H-F

    2016-11-01

    Randomized controlled trials (RCTs) have investigated the use of colchicine and conventional therapy for reducing the recurrence of pericarditis in patients with acute pericarditis or post-pericardiotomy syndrome. However, the benefits of these treatments are variable. Studies were retrieved from PubMed, the Cochrane Library, and the EMBASE database. We identified nine RCTs with 1832 patients and a mean follow-up of 13.1 months. Overall, colchicine therapy significantly decreased the risk of pericarditis recurrence (odds ratio, OR 0.42; 95 % confidence interval, CI 0.33-0.52; P Colchicine therapy was associated with significantly lower rates of pericarditis-associated rehospitalization (OR 0.29; 95 % CI 0.16-0.53; P colchicine group (relative risk, RR 1.48; 95 % CI, 1.06-2.07; P = 0.02; I 2  = 0.0 %). Subgroup analysis showed that recurrence of pericarditis was significantly lower in the colchicine therapy group, irrespective of prednisone use and the cause of pericarditis. Colchicine significantly decreases the rate of pericarditis recurrence, regardless of prednisone use and the cause of pericarditis. Larger studies are needed to confirm this effect.

  14. Approach to the patients with inadequate response to colchicine in familial Mediterranean fever.

    Science.gov (United States)

    Gül, Ahmet

    2016-04-01

    Familial Mediterranean fever (FMF) is the most common form of monogenic autoinflammatory conditions, and response to colchicine has been considered as one of its distinctive features among other hereditary periodic fever disorders. Prophylactic colchicine has been shown to be effective in the prevention of inflammatory attacks and development of amyloidosis. However, the highest tolerable doses of colchicine may not be adequate enough to manage these goals in approximately 5% of FMF patients. Inadequate response to colchicine in fully compliant FMF patients may be associated with genetic and/or environmental factors affecting disease severity and colchicine bioavailability. Clarification of the molecular pathogenic mechanisms of FMF has revealed that interleukin-1 beta (IL-1β) cytokine is the most likely target to attack, and several case reports and case series have already documented the efficacy and safety of available anti-IL-1 agents, such as anakinra, rilonacept, and canakinumab in those patients inadequately responding to colchicine. Characterization and early identification of those FMF patients with uncontrolled inflammatory activity have become more important after the availability of new treatment options for the prevention of disease-associated complications and permanent damages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Colchicine for prevention and treatment of cardiac diseases: A meta-analysis.

    Science.gov (United States)

    Papageorgiou, Nikolaos; Briasoulis, Alexandros; Lazaros, George; Imazio, Massimo; Tousoulis, Dimitris

    2017-02-01

    Colchicine has been suggested to be beneficial in preventing recurrent pericarditis. The goal of this study was to review all randomized controlled trials that assess the use of colchicine for the prevention and treatment of cardiac diseases. We performed a meta-analysis of the effects of colchicine on pericarditis, postpericardiotomy syndrome and postprocedural atrial fibrillation recurrence, in-stent restenosis, gastrointestinal adverse effects, and treatment discontinuation rates. We conducted an EMBASE and MEDLINE search for prospective controlled trials. We identified 17 prospective controlled randomized studies with 2082 patients that received colchicine and 1982 controls with an average follow-up duration of 12 months. Treatment with colchicine is associated with reduced risk of pericarditis recurrence/postpericardiotomy syndrome (OR: 0.37; 95% CI: 0.29-0.47; Pcolchicine (OR: 2.6; 95% CI: 1.82-3.72; Pcolchicine. Colchicine appears to be efficacious and well tolerated for recurrent pericarditis/postpericardiotomy syndrome and recurrence of postprocedural atrial fibrillation. However, its efficacy may be limited by its gastrointestinal adverse events and treatment discontinuation rates particularly in postoperative patients. © 2016 John Wiley & Sons Ltd.

  16. Pharmacotherapeutic considerations for using colchicine to treat idiopathic pericarditis in the USA.

    Science.gov (United States)

    Schwier, Nicholas C

    2015-10-01

    The clinical significance of colchicine in the treatment of acute idiopathic (viral) pericarditis (IP) was only elucidated less than a decade ago. Multiple trials have shown the benefit of colchicine in decreasing the rate of recurrence, primarily in the European population. However, the colchicine formulation used in these trials is not available in Western countries such as the USA. In the USA, two formulations are available: the 0.6 mg capsule and the 0.6 mg tablet. As a result, higher doses than administered in the European trials must be utilized to treat IP. However, the use of these dosage forms has never been studied in the treatment of IP. Pharmacokinetic and pharmacodynamic knowledge of colchicine germane to clinicians such as drug disposition and drug-drug or drug-disease interactions have not been extensively reviewed in recent years. Furthermore, the safety of colchicine in the treatment of IP has not been extensively studied, and literature regarding adverse drug events originates from data in patients treated for familial Mediterranean fever and gout. This review will help the clinician understand pharmacotherapeutic considerations and thereby optimize therapy and ensure patient safety when using colchicine to treat IP.

  17. Effects of colchicine on pericardial diseases: a review of the literature and current evidence

    Directory of Open Access Journals (Sweden)

    Syed Raza Shah

    2016-07-01

    Full Text Available Colchicine, extracted from the colchicum autumnale plant, used by the ancient Greeks more than 20 centuries ago, is one of the most ancient drugs still prescribed even today. The major mechanism of action is binding to microtubules thereby interfering with mitosis and subsequent modulation of polymorphonuclear leukocyte function. Colchicine has long been of interest in the treatment of cardiovascular disease; however, its efficacy and safety profile for specific conditions have been variably established in the literature. In the subset of pericardial diseases, colchicine has been shown to be effective in recurrent pericarditis and post-pericardiotomy syndrome (PPS. The future course of treatment and management will therefore highly depend on the results of the ongoing large randomized placebo-controlled clinical trial to evaluate the efficacy and safety of colchicine for the primary prevention of several postoperative complications and in the perioperative period. Also, given the positive preliminary outcomes of colchicine usage in pericardial effusions, the future therapeutical use of colchicine looks promising. Further study is needed to clarify its role in these disease states, as well as explore other its role in other cardiovascular conditions.

  18. Vortex rings

    CERN Document Server

    Akhmetov, D G

    2009-01-01

    This text on vortex rings covers their theoretical foundation, systematic investigations, and practical applications such as the extinction of fires at gushing oil wells. It pays special attention to the formation and motion of turbulent vortex rings.

  19. Two Cases of Acute Leukopenia Induced by Colchicine with Concurrent Immunosuppressants Use in Behçet's Disease

    Science.gov (United States)

    Lee, Kyu-Yeop; Kim, Do Young; Chang, Jae Yong

    2008-01-01

    Colchicine-induced leukopenia usually occurrs in intentional or accidental overdoses or inappropriate use in combination with intravenous and oral colchine; however, there have been several reports of hematologic toxicity in short-term and small-dose colchicine medication courses. We present two cases of leukopenia induced by colchicine use concurrent with immunosuppressants in Behçet's disease. We postulate that the mechanism of colchicine-induced leukopenia might be the destruction of circulating leukocytes and an inhibition of leukocyte production by the immediate and direct toxic effect of colchicine on idiosyncrasies unique to each patient. The concurrently administered immunosuppressant might decrease the threshold for hematologic toxicity of colchicine in the leukocytes and their precursor cells. PMID:18306487

  20. BZML, a novel colchicine binding site inhibitor, overcomes multidrug resistance in A549/Taxol cells by inhibiting P-gp function and inducing mitotic catastrophe.

    Science.gov (United States)

    Bai, Zhaoshi; Gao, Meiqi; Zhang, Huijuan; Guan, Qi; Xu, Jingwen; Li, Yao; Qi, Huan; Li, Zhengqiang; Zuo, Daiying; Zhang, Weige; Wu, Yingliang

    2017-08-28

    Multidrug resistance (MDR) interferes with the efficiency of chemotherapy. Therefore, developing novel anti-cancer agents that can overcome MDR is necessary. Here, we screened a series of colchicine binding site inhibitors (CBSIs) and found that 5-(3, 4, 5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl) imidazol (BZML) displayed potent cytotoxic activity against both A549 and A549/Taxol cells. We further explored the underlying mechanisms and found that BZML caused mitosis phase arrest by inhibiting tubulin polymerization in A549 and A549/Taxol cells. Importantly, BZML was a poor substrate for P-glycoprotein (P-gp) and inhibited P-gp function by decreasing P-gp expression at the protein and mRNA levels. Cell morphology changes and the expression of cycle- or apoptosis-related proteins indicated that BZML mainly drove A549/Taxol cells to die by mitotic catastrophe (MC), a p53-independent apoptotic-like cell death, whereas induced A549 cells to die by apoptosis. Taken together, our data suggest that BZML is a novel colchicine binding site inhibitor and overcomes MDR in A549/Taxol cells by inhibiting P-gp function and inducing MC. Our study also offers a new strategy to solve the problem of apoptosis-resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. In vivo uptake of carbon-14-colchicine for identification of tumor multidrug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, B.M.; Rosa, E.; Biedler, J.L. [Nuclear Medicine Research Lab., New York, NY (United States)] [and others

    1994-07-01

    A major limitation in the treatment of cancer with natural product chemotherapeutic agents is the development of multidrug resistance (MDR). Multidrug resistance is attributed to enhanced expression of the multidrug resistance gene MDR1. Colchicine (CHC) is known to be one of the MDR drugs. The authors have previously demonstrated that it is possible to distinguish multidrug resistant tumors from the multidrug-sensitive tumors in vivo on the basis of tritium ({sup 3}H) uptake following injection of {sup 3}H-CHC. The present studies were carried out in xenografted animals using {sup 14}C-CHC which may be more indicative of {sup 11}C-labeled CHC distribution with regard to circulating metabolites, since metabolic processes following injection of (ring C, methoxy-{sup 11}C)-CHC may produce significant amounts of circulating 1l-carbon fragments (i.e., methanol and/or formaldehyde). Experiments were carried out at a dose of 2 mg/kg. Activity concentration per injected dose was approximately twice as great in sensitive as in resistant tumors (p < 0.05) at 60 min following intravenous injection of {sup 14}C-CHC. About 75% of total activity was CHC in the sensitive tumors. The findings are further confirmed by the quantitative autoradiographic evaluation of resistant and sensitive tumors. These studies confirm our previous observations that it is possible to noninvasively distinguish multidrug-resistant tumors from sensitive tumors in vivo based on uptake of an injected MDR drug using a{sup 14}C-labeled CHC at the same position and of comparable specific activity to a {sup 11}C-CHC tracer used for PET imaging. 16 refs., 5 figs., 2 tabs.

  2. Planetary Rings

    Science.gov (United States)

    Tiscareno, Matthew S.

    Planetary rings are the only nearby astrophysical disks and the only disks that have been investigated by spacecraft (especially the Cassini spacecraft orbiting Saturn). Although there are significant differences between rings and other disks, chiefly the large planet/ring mass ratio that greatly enhances the flatness of rings (aspect ratios as small as 10- 7), understanding of disks in general can be enhanced by understanding the dynamical processes observed at close range and in real time in planetary rings.We review the known ring systems of the four giant planets, as well as the prospects for ring systems yet to be discovered. We then review planetary rings by type. The A, B, and C rings of Saturn, plus the Cassini Division, comprise our solar system's only dense broad disk and host many phenomena of general application to disks including spiral waves, gap formation, self-gravity wakes, viscous overstability and normal modes, impact clouds, and orbital evolution of embedded moons. Dense narrow rings are found both at Uranus (where they comprise the main rings entirely) and at Saturn (where they are embedded in the broad disk) and are the primary natural laboratory for understanding shepherding and self-stability. Narrow dusty rings, likely generated by embedded source bodies, are surprisingly found to sport azimuthally confined arcs at Neptune, Saturn, and Jupiter. Finally, every known ring system includes a substantial component of diffuse dusty rings.Planetary rings have shown themselves to be useful as detectors of planetary processes around them, including the planetary magnetic field and interplanetary impactors as well as the gravity of nearby perturbing moons. Experimental rings science has made great progress in recent decades, especially numerical simulations of self-gravity wakes and other processes but also laboratory investigations of coefficient of restitution and spectroscopic ground truth. The age of self-sustained ring systems is a matter of

  3. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study.

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-12-01

    Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.

  4. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    Science.gov (United States)

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  5. Competitive binding of phenylbutazone and colchicine to serum albumin in multidrug therapy: A spectroscopic study

    Science.gov (United States)

    Sułkowska, A.; Maciążek-Jurczyk, M.; Bojko, B.; Równicka, J.; Zubik-Skupień, I.; Temba, E.; Pentak, D.; Sułkowski, W. W.

    2008-06-01

    The binding sites for phenylbutazone and colchicine were identified in tertiary structure of bovine and human serum albumin with the use of spectrofluorescence analysis. It was found that phenylbutazone has two binding sites in both sera albumins (HSA and BSA), while colchicine has one binding site in BSA as well as in HSA. The comparison of the quenching effect of BSA and HSA fluorescence by phenylbutazone and colchicine allows us to identify subdomain IIA in protein as the binding site for these two drugs. In this subdomain tryptophan 214 is located. The participation of tyrosyl and tryptophanyl residues of protein was also estimated in the drug-albumin complex. The comparison of quenching of fluorescence of HSA and BSA excited at 280 nm with that at 295 nm allowed us to state that the participation of tyrosyl residues of albumin in the phenylbutazone-serum albumin interaction is significant. The analysis of quenching of fluorescence of BSA in the binary and ternary systems showed that phenylbutazone does not affect the complex formed between colchicine and BSA. Similarly, colchicine has no effect on the Phe-BSA complex. However marked differences were observed for the complex with HSA. On the basis of Ka and KQ values it was concluded that colchicine may probably cause displacement of phenylbutazone from its complex with serum albumin (SA). Static and dynamic quenching for the binary and ternary systems is also discussed. The competition of phenylbutazone and colchicine in binding to serum albumin should be taken into account in the multi-drug therapy.

  6. Induction of micronuclei and nuclear abnormalities by cyclophosphamide and colchicine in Xenotoca melanosoma (Pisces, Goodeidae) from Lake La Alberca in Michoacan, Mexico.

    Science.gov (United States)

    Zavala-Aguirre, Jose Luis; Torres-Bugarin, Olivia; Buelna-Osben, Hector Rene; Flores-Kehn, Lola Paulina; Ramos-Ibarra, Maria Luisa; Zuniga-Gonzalez, Guillermo; Ogura, Tetsuya

    2010-01-01

    This study is a follow-up of previous research in which we described the frequency of spontaneous micronucleated erythrocytes (MNE) in the Goodeid Xenotocoa melanosoma collected from Lake La Alberca, located in the state of Michoacan, Mexico. In the present work, we measured micronuclei (MN) and nuclear abnormalities (NA) in erythrocytes of peripheral blood. Bioassays taken at 24 or 96 hours in either the cyclophosfamide (CP) or colchicine (COL) showed a significant increase in MN and BC (P values ranging from 0.0499 to 0.0036) compared with information from wild organisms collected over 3 years. Concentrationdependent and time-dependent responses support the proposal of using endemic Xenotoca melanosoma as a bioindicator of genotoxicity and cytotoxicity with a high transcendence for the health of the entire ecosystem and evaluation of the Lerma-Chapala watershed.

  7. Evaluation of commercial ginkgo and echinacea dietary supplements for colchicine using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Li, Wenkui; Sun, Yongkai; Fitzloff, John F; van Breemen, Richard B

    2002-09-01

    In response to concerns that commercial dietary supplements containing Ginkgo biloba (ginkgo) and Echinacea purpurea, Echinacea angustifolia, or Echinacea pallida (echinacea) might be contaminated with colchicine, a highly selective and sensitive assay was developed for colchicine that is based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The method utilizes reversed-phase HPLC separation of compounds in a methanolic extract of the dietary supplement or botanical sample followed by positive ion electrospray ionization with collision-induced dissociation and multiple reaction monitoring of three characteristic fragmentation pathways of the protonated molecule of colchicine, m/z 400 --> 358, 400 --> 326, and 400 --> 310. The minimal detectable concentration of colchicine using this assay was 10 pg on-column, which is equivalent to 20 ppb colchicine in a 0.5 g ginkgo leaf sample. The method was validated by analyzing 0.5 g samples spiked with colchicine and determining the recovery. A total of 26 commercial ginkgo and echinacea dietary supplements were purchased from pharmacies in Chicago, IL, and analyzed for colchicine. In contrast to a recent report, no colchicine was detected in any of the samples. In addition, authenticated ginkgo leaves were collected, assayed, and found to contain no colchicine, which is consistent with the botanical literature. On the basis of the results obtained using this new LC-MS-MS assay, which is more sensitive and more selective than previously published methods for colchicine, we find no cause for concern regarding colchicine contamination of ginkgo or echinacea dietary supplements.

  8. Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population.

    Science.gov (United States)

    Kesselheim, Aaron S; Franklin, Jessica M; Kim, Seoyoung C; Seeger, John D; Solomon, Daniel H

    2015-11-01

    A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.

  9. Effects of colchicine and irradiation in Spathoglottis 'yellow' (Orchidiaceae)

    International Nuclear Information System (INIS)

    Rosario, T.L.; Maningas, A.D.

    1998-01-01

    Spathoglottis 'Yellow' is usually grown as a flowering plant. The big yellow flowers are borne on thin long spikes and if improved can be used as cut flowers. One method to accomplish this is by mutation breeding. One set of embryos from selfed flowers were cultured in germinating media with colchicines, another set were irradiated with gamma rays and another one treated with colchicine and gamma rays combined. Germination of embryos grown in media with 0.01 percent and 0.05 percent colchicine germinated 5 weeks later than the control. In addition, they did not develop roots. Plants in 0.05 percent colchicine are shorter with thicker leaves. On the other hand, embryos irradiated with gamma rays (500 r, 800 r, 1 Kr and 2 Kr) germinated 5 months after planting. Although no root formation was observed among the treated plants, shoot development is the same as the control. Combined colchicine and irradiation treatments caused much delayed germination (10 months) and no root formation. Higher doses resulted in failure to germinate

  10. Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis.

    Science.gov (United States)

    Wang, Ming-Xuan; Deng, Xiao-Long; Mu, Bing-Yao; Cheng, Yong-Jing; Chen, Ying-Juan; Wang, Qian; Huang, Jia; Zhou, Rong-Wei; Huang, Ci-Bo

    2016-09-01

    Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70-1.13; p = 0.33, I (2) = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52-1.13; p = 0.18, I (2) = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF.

  11. Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori.

    Science.gov (United States)

    Cohen, Oren; Locketz, Garrett; Hershko, Alon Y; Gorshtein, Alexander; Levy, Yair

    2015-11-01

    Chronic administration of colchicine remains a mainstay of therapy for patients with Familial Mediterranean Fever (FMF). As this medication is a strong CYP3A4 inhibitor, it has the potential to interact with many routinely used medications. One such medication is clarithromycin, itself a strong inhibitor of the same enzyme, and a typical choice for triple therapy eradication of H. pylori. Various sequelae of colchicine-clarithromycin interaction have been documented and can be expected by prescribing physicians, with rhabdomyolysis, though rare, being among the most serious. Review of cases from a tertiary academic medical center and full PubMed/MEDLINE literature review. Despite the prevalence of diseases treated with clarithromycin and the expected drug interaction with colchicine, only two cases in the literature document clinical rhabdomyolysis due to colchicine-clarithromycin interaction. In neither case, however, were patients undergoing treatment for FMF. Herein, we describe the first two cases in the literature of clinical rhabdomyolysis in FMF patients under colchicine therapy after administration of clarithromycin as part of therapy treating H. pylori infection.

  12. Reduction of intraarticular adhesion by topical application of colchicine following knee surgery in rabbits

    Science.gov (United States)

    Sun, Yu; Liang, Yuan; Hu, Jinlong; Wang, Jingcheng; Wang, Daxin; Li, Xiaolei; Yan, Lianqi

    2014-01-01

    The aim of this study was to investigate the efficacy of topical application of colchicine in reducing intraarticular adhesion in rabbits. Thirty-six rabbits were randomly and equally divided into three groups. An approximately 10 × 10 mm2 area of cortical bone was removed from both sides of the left femoral condyle, and the cancellous bone underneath was exposed. Cotton pads soaked with different concentrations of colchicine or saline were applied to the decorticated areas for 10 minutes. The surgical limb was fixed in a flexed position for 4 weeks postoperatively. To evaluate knee intraarticular adhesion, we performed macroscopic evaluation, histological and collagen density analyses, hydroxyproline content determination, fibroblast counting and densitometric analyses. The results showed that loose collagen tissues with little or no adhesion were present around the decorticated areas in the group treated with 0.5 mg/ml colchicine. The intraarticular adhesion score, hydroxyproline content, number of fibroblasts and densitometric value in this group were also significantly lower than those in the other groups. There was moderate intraarticular adhesion in the group treated with 0.1 mg/ml colchicine. However, dense scar tissue with dense adhesions was found in the control group. In conclusion, topical application of 0.5 mg/ml colchicine may reduce knee intraarticular adhesion. PMID:25245566

  13. Colchicine may assist in reducing granulation tissue in junctional epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Minhee Kim, MBBS

    2016-06-01

    Full Text Available Epidermolysis bullosa (EB is a rare, inherited blistering genodermatosis. Patients with junctional EB (JEB due to LAMB3 mutations have widespread blisters and erosions of skin, mucosae, and nails, creating significant physical, emotional, and psychosocial burdens. Here we report the use of colchicine for ameliorating hypergranulating wounds in a 41-year-old female with JEB generalized intermediate. Her skin wounds and granulation tissue gradually exacerbated under silicone dressings such that she became profoundly anemic. Subsequently, she was commenced on colchicine 500 μg daily on the basis that it may inhibit cell proliferation and be anti-inflammatory. After a 6-month trial of colchicine, she had an objective and subjective improvement in her validated EB Disease Activity and Scarring Index activity and damage scores and Quality Of Life in EB score with less skin erosions, granulation tissue, and erythema. In addition, her anemia resolved. She denied any gastrointestinal side effects. The exact mechanism of colchicine in assisting reduction of the blistering, erosions, and granulation in JEB is unclear, but the anti-inflammatory and antimitotic properties of colchicine may be partially responsible for this process.

  14. To Investigate the Effect of Colchicine in Prevention of Adhesions Caused by Serosal Damage in Rats

    Directory of Open Access Journals (Sweden)

    İhsan Yıldız

    2015-01-01

    Full Text Available Introduction and Aim. Adhesion formation is a process which starts with an inflammation caused by a number of factors and eventually results in fibrosis. Colchicine prevents adhesion formation which is antifibrous process. The effectivity of colchicine in the prevention of adhesions was investigated. Materials and Methods. A total of 36 rats were equally divided into three groups: (I control group 1 (n=12, (II abrasion group 2 (n=12, and (III abrasion + colchicine group 3 (n=12. Group 1 underwent laparotomy and was orally given physiological serum 2 cc/day for 10 days. In Group 2, injury was created in the cecum serosa following laparotomy and they were orally given physiological serum 2 cc/day for 10 days. In Group 3, injury was created in the cecum serosa following laparotomy and the rats were orally given colchicine 50 mcg kg/day mixed with physiological serum 2 cc/day for 10 days. Laparotomy was performed and adhesions were examined both macroscopically and microscopically. Both macroscopic and microscopic examinations were performed using Zühlke’s score. Results. A significant difference was observed among the adhesion scores of the groups both macroscopically and microscopically. Macroscopic score was lower in group 3 than group 2. Microscopic score was lower in group 3 than group 2. Conclusion. Oral administration of colchicine is effective in the prevention of adhesions.

  15. Mutagenic influences of colchicine on phenological and molecular diversity of Calendula officinalis L.

    Science.gov (United States)

    El-Nashar, Y I; Ammar, M H

    2016-04-26

    Six different colchicine concentrations: 0, 400, 800, 1200, 1600, and 2000 ppm, in combination with four soaking time treatments (1, 2, 3, and 4 h), were selected to assess the effects on germination, vegetative growth, and flower yield components in calendula plants. The molecular diversity among the treatments was assessed using ten SRAP marker combinations. Seed soaking in colchicine significantly enhanced both the fresh and the dry shoot and root masses, flowering date, number of flowers per plant, and flower diameter. At 1200-ppm colchicine combined with a 4-h soaking time, a superior effect on seed germination was observed, whereas 800 ppm for 4 h produced the highest number of flowers and the largest flower diameter. The earliest flowering time was found at 800 ppm combined with a short soaking time (1 h), while the 4-h soaking time with 800 ppm, is recommended for growing calendula outdoors, since it enhances flower development. At the molecular level, 752 fragments were successfully amplified using the SRAP primers, with 280 genetic loci found throughout the calendula genome. The polymorphism percentage ranged from 79 to 100% and the polymorphic information content (PIC) values ranged between 0.85 and 0.97. The high number of detected loci and PIC values suggests a great power of SRAP markers in detecting mutant molecular diversity. Our results clearly show the existence of genetic variation among colchicine treated calendula plants and the clustering of the studied mutants was concordant with the colchicine concentration used.

  16. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Science.gov (United States)

    Bañales-Martínez, Luis R.; Lemus-Varela, María de Lourdes; Trujillo, Xóchitl; Sánchez-Parada, María G.; Armendáriz-Borunda, Juan; Zúñiga-González, Guillermo M.

    2016-01-01

    Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects. PMID:28018917

  17. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Directory of Open Access Journals (Sweden)

    Belinda C. Gómez-Meda

    2016-01-01

    Full Text Available Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs and micronucleated polychromatic erythrocytes (MNPCEs in the samples from pups in the experimental groups (P<0.02 and increased MNPCE frequencies in the samples from the dams (P<0.05. These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.

  18. Low dose Colchicine in prevention of atrial fibrillation after coronary artery bypass graft: a double blind clinical trial

    Directory of Open Access Journals (Sweden)

    Mahmoodreza Sarzaeem

    2014-06-01

    Conclusion: Colchicine is an anti-inflammatory medication and has very few side effects at low doses. According to the 48% reduction in the incidence of atrial fibrillation in Colchicine patients undergoing coronary artery bypass grafting surgery, this drug can be prescribed as a prophylaxis for prevention of post-CABG atrial fibrillation.

  19. Storage rings

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Gerald K.

    1963-04-15

    The development of storage rings is discussed. Advantages of such devices are pointed out as well as their limits, requirements, and design and fabrication problems. Information gained by the operation of small electron storage rings is included, and three experiments are proposed for colliding-beam facilities. (D.C.W.)

  20. Tubulin inhibitors targeting the colchicine binding site: a perspective of privileged structures.

    Science.gov (United States)

    Li, Wenlong; Sun, Honghao; Xu, Shengtao; Zhu, Zheying; Xu, Jinyi

    2017-10-01

    The vital roles of microtubule in mitosis and cell division make it an attractive target for antitumor therapy. Colchicine binding site of tubulin is one of the most important pockets that have been focused on to design tubulin-destabilizing agents. Over the past few years, a large number of colchicine binding site inhibitors (CBSIs) have been developed inspired by natural products or synthetic origins, and many moieties frequently used in these CBSIs are structurally in common. In this review, we will classify the CBSIs into classical CBSIs and nonclassical CBSIs according to their spatial conformations and binding modes with tubulin, and highlight the privileged structures from these CBSIs in the development of tubulin inhibitors targeting the colchicine binding site.

  1. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.

    Science.gov (United States)

    Imazio, Massimo; Brucato, Antonio; Ferrazzi, Paolo; Pullara, Alberto; Adler, Yehuda; Barosi, Alberto; Caforio, Alida L; Cemin, Roberto; Chirillo, Fabio; Comoglio, Chiara; Cugola, Diego; Cumetti, Davide; Dyrda, Oleksandr; Ferrua, Stefania; Finkelstein, Yaron; Flocco, Roberto; Gandino, Anna; Hoit, Brian; Innocente, Francesco; Maestroni, Silvia; Musumeci, Francesco; Oh, Jae; Pergolini, Amedeo; Polizzi, Vincenzo; Ristic, Arsen; Simon, Caterina; Spodick, David H; Tarzia, Vincenzo; Trimboli, Stefania; Valenti, Anna; Belli, Riccardo; Gaita, Fiorenzo

    2014-09-10

    Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in

  2. Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin

    Directory of Open Access Journals (Sweden)

    Ashwani Sharma

    2017-06-01

    Full Text Available Quinolin-6-yloxyacetamides (QAs are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole. Together, our data establish QAs as colchicine-site ligands and explain the molecular mechanism of microtubule destabilization by this class of compounds. They further extend our structural knowledge on antitubulin agents and thus should aid in the development of new strategies for the rational design of ligands against multidrug-resistant cancer cells.

  3. ZnT3 Gene Deletion Reduces Colchicine-Induced Dentate Granule Cell Degeneration

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2017-10-01

    Full Text Available Our previous study demonstrated that colchicine-induced dentate granule cell death is caused by blocking axonal flow and the accumulation of intracellular zinc. Zinc is concentrated in the synaptic vesicles via zinc transporter 3 (ZnT3, which facilitates zinc transport from the cytosol into the synaptic vesicles. The aim of the present study was to identify the role of ZnT3 gene deletion on colchicine-induced dentate granule cell death. The present study used young (3–5 months mice of the wild-type (WT or the ZnT3−/− genotype. Colchicine (10 µg/kg was injected into the hippocampus, and then brain sections were evaluated 12 or 24 h later. Cell death was evaluated by Fluoro-Jade B; oxidative stress was analyzed by 4-hydroxy-2-nonenal; and dendritic damage was detected by microtubule-associated protein 2. Zinc accumulation was detected by N-(6-methoxy-8-quinolyl-para-toluenesulfonamide (TSQ staining. Here, we found that ZnT3−/− reduced the number of degenerating cells after colchicine injection. The ZnT3−/−-mediated inhibition of cell death was accompanied by suppression of oxidative injury, dendritic damage and zinc accumulation. In addition, ZnT3−/− mice showed more glutathione content than WT mice and inhibited neuronal glutathione depletion by colchicine. These findings suggest that increased neuronal glutathione by ZnT3 gene deletion prevents colchicine-induced dentate granule cell death.

  4. Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

    Directory of Open Access Journals (Sweden)

    Camila Stuchi Zarpelon

    2016-01-01

    Full Text Available Abstract Background: The high prevalence of atrial fibrillation (AF in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271. There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363 and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490. However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007. Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

  5. Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization.

    Science.gov (United States)

    Zarpelon, Camila Stuchi; Netto, Miguel Chomiski; Jorge, José Carlos Moura; Fabris, Cátia Carolina; Desengrini, Dieli; Jardim, Mariana da Silva; Silva, Diego Guedes da

    2016-07-01

    The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

  6. Activated charcoal significantly reduces the amount of colchicine released from Gloriosa superba in simulated gastric and intestinal media.

    Science.gov (United States)

    Zawahir, Shukry; Gawarammana, Indika; Dargan, Paul I; Abdulghni, Mahfoudh; Dawson, Andrew H

    2017-09-01

    Poisoning with Gloriosa superba, a plant containing colchicine, is common in Sri Lanka. This study was to estimate release of colchicine from 5 g of different parts of Gloriosa superba in simulated gastric and intestinal media, and examine the binding efficacy of activated charcoal (AC) to colchicine within this model. A USP dissolution apparatus-II was used to prepare samples for analysis of colchicine using HPLC. Cumulative colchicine release from tuber in gastric media at 120 minutes was significantly higher (2883 μg/g) than in intestinal media (1015 μg/g) (p colchicine concentration over 2 hours from tuber, leaves and trunk in gastric medium was 2883.15 ± 1295.63, 578.25 ± 366.26 and 345.60 ± 200.08 μg/g respectively and the release in intestinal media was 1014.75 ± 268.16, 347.40 ± 262.61 and 251.55 ± 285.72 μg/g respectively. Introduction of 50 g of AC into both media made colchicine undetectable (colchicine. The colchicine release and elapse time to achieve saturated, equilibrium dissolution mainly depends on physicochemical properties of plant part. Significant in vitro binding of colchicine to AC suggests that AC has a role in decontamination of patients presenting to hospital after ingestion of Gloriosa superba.

  7. Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-04-01

    To investigate the potential interaction between grapefruit juice (GFJ) and the oral microtubule polymerization inhibitor colchicine, a P-gp and CYP3A4 substrate. Colchicine intestinal epithelial transport was investigated across Caco-2 cell monolayers in both AP-BL and BL-AP directions, in the absence/presence of known P-gp inhibitors (verapamil and quinidine). The concentration-dependent effects of GFJ and its major constituents (6'-7'-dihydroxybergamottin, naringin and naringenin) on colchicine Caco-2 mucosal secretion were examined. The effect of GFJ on colchicine intestinal-permeability was then investigated in-situ in the rat perfusion model, in both jejunum and ileum. Colchicine exhibited 20-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion, which was reduced by verapamil/quinidine. Colchicine AP-BL permeability was increased and BL-AP was decreased by GFJ in a concentration-dependent manner (IC(50) values of 0.75% and 0.46% respectively), suggesting inhibition of efflux transport, rather than metabolizing enzyme. Similar effects obtained following pre-experiment incubation with GFJ, even though the juice was not present throughout the transepithelial study. 6'-7'-Dihydroxybergamottin, naringin and naringenin displayed concentration-dependent inhibition on colchicine BL-AP secretion (IC(50) values of 90, 592 and 11.6 microM respectively). Ten percent GFJ doubled colchicine rat in-situ ileal permeability, and increased 1.5-fold jejunal permeability. The data suggest that GFJ may augment colchicine oral bioavailability. Due to colchicine narrow therapeutic-index and severely toxic side-effects, awareness of this interaction is prudent.

  8. Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents.

    Science.gov (United States)

    Eroglu, Fehime Kara; Beşbaş, Nesrin; Topaloglu, Rezan; Ozen, Seza

    2015-10-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the

  9. Determinantal rings

    CERN Document Server

    Bruns, Winfried

    1988-01-01

    Determinantal rings and varieties have been a central topic of commutative algebra and algebraic geometry. Their study has attracted many prominent researchers and has motivated the creation of theories which may now be considered part of general commutative ring theory. The book gives a first coherent treatment of the structure of determinantal rings. The main approach is via the theory of algebras with straightening law. This approach suggest (and is simplified by) the simultaneous treatment of the Schubert subvarieties of Grassmannian. Other methods have not been neglected, however. Principal radical systems are discussed in detail, and one section is devoted to each of invariant and representation theory. While the book is primarily a research monograph, it serves also as a reference source and the reader requires only the basics of commutative algebra together with some supplementary material found in the appendix. The text may be useful for seminars following a course in commutative ring theory since a ...

  10. ring system

    African Journals Online (AJOL)

    1,3,2-DIAZABORACYCLOALKANE. RING SYSTEM. Negussie Retta" and Robert H. Neilson. 'Department of Chemistry, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia. Department of Chemistry, Texas Christian University.

  11. Vascular ring

    Science.gov (United States)

    ... trachea) and esophagus can lead to breathing and digestive problems. The more the ring presses down, the more severe the symptoms will be. Breathing problems may include: ... Digestive symptoms are rare, but may include: Choking Difficulty ...

  12. Impact of Periprocedural Colchicine on Postprocedural Management in Patients Undergoing a Left Atrial Appendage Ligation Using LARIAT.

    Science.gov (United States)

    Gunda, Sampath; Reddy, Madhu; Nath, Jayant; Nagaraj, Hosakote; Atoui, Moustapha; Rasekh, Abdi; Ellis, Christopher R; Badhwar, Nitish; Lee, Randall J; DI Biase, Luigi; Mansour, Moussa; Ruskin, Jeremy N; Natale, Andrea; Earnest, Matthew; Lakkireddy, Dhanunjaya R

    2016-01-01

    Left atrial appendage (LAA) can be effectively and safely excluded using a novel percutaneous LARIAT ligation system. However, due to pericardial catheter manipulation and LAA ligation and subsequent necrosis, postprocedural course is complicated by pericarditis. We intended to evaluate the preprocedural use of colchicine on the incidence of postprocedural pericardial complications. In this multicenter observational study, we included all consecutive patients who underwent LARIAT procedure at the participating centers. Many patients received periprocedural colchicine at the discretion of the physician. We compared the postprocedural outcomes of patients who received prophylactic periprocedural colchicine (colchicine group) with those who did not receive colchicine (standard group). A total of 344 consecutive patients, 243 in the "colchicine group" and 101 in the "standard group," were included. The mean age, median CHADS2VASc score, and HASBLED scores were 70 ± 11 years, 3 ± 1.7, and 3 ± 1.1, respectively. There were no significant differences in major baseline characteristics between the two groups. Severe pericarditis was significantly lower in the "colchicine group" compared to the "standard group" (10 [4%] vs. 16 [16%] Pcolchicine group, compared to the standard group, had lesser pericardial drain output (186 ± 84 mL vs. 351 ± 83, Pcolchicine periprocedurally was associated with significant reduction in postprocedural pericarditis and associated complications. © 2015 Wiley Periodicals, Inc.

  13. Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats

    International Nuclear Information System (INIS)

    Pavelka, M.; Gangl, A.

    1983-01-01

    The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, researchers have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [ 14 C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that colchicine causes significant changes in enterocyte ultrastructure and colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte

  14. Induced Polyploidy in Diploid Ornamental Ginger (Hedychium muluense) Using Colchicine and Oryzalin

    Science.gov (United States)

    The ploidy level of H. muluense, a diploid (2n = 2x = 34) and dwarf ornamental ginger species, has been determined and is reported for the first time. Oryzalin and colchicine were successfully used to induce polyploidy in Hedychium muluense in vitro. Embryogenic cell lines were treated with oryzalin...

  15. Interaction of Pseudolaric Acid B with The Colchicine Site of Tubulin

    Science.gov (United States)

    Sarkar, Taradas; Nguyen, Tam Luong; Su, Zhi-Wei; Hao, Jun; Bai, Ruoli; Gussio, Rick; Qiu, Samuel X.; Hamel, Ernest

    2012-01-01

    We purified pseudolaric acid B (PAB) from the root and stem bark of Pseudolarix kaempferi (Lindl.) Gorden. Confirming previous findings, we found that the compound had high nanomolar IC50 antiproliferative effects in several cultured cell lines, causing mitotic arrest and the disappearance of intracellular microtubules. PAB strongly inhibited tubulin assembly (IC50, 1.1 μM) but weakly inhibited the binding of colchicine to tubulin, as demonstrated by fluorescence and with [3H]colchicine. Kinetic analysis demonstrated that the mechanism of inhibition was competitive, with an apparent Ki of 12-15 μM. Indirect studies demonstrated that PAB bound rapidly to tubulin and dissociated more rapidly from tubulin than the colchicine analog 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl)tropone, whose complex with tubulin is known to have a half-life of 17 s at 37 °C. We modeled PAB into the colchicine site of tubulin, using the crystal structure 1SA0 that contains two αβ-tubulin heterodimers, both bound to a colchicinoid and to a stathmin fragment. The binding model of PAB revealed common pharmacophoric features between PAB and colchicinoids, not readily apparent from their chemical structures. PMID:22634405

  16. Enantiomeric separation of the antiuremic drug colchicine by electrokinetic chromatography. Method development and quantitative analysis.

    Science.gov (United States)

    Menéndez-López, Nuria; Valimaña-Traverso, Jesús; Castro-Puyana, María; Salgado, Antonio; García, María Ángeles; Marina, María Luisa

    2017-05-10

    Two analytical methodologies were developed by CE enabling the enantiomeric separation of colchicine, an antiuremic drug commercialized as pure enantiomer. Succinyl-γ-CD and Sulfated-γ-CD were selected as chiral selectors after a screening with different anionic CDs. Under the optimized conditions, chiral resolutions of 5.6 in 12min and 3.2 in 8min were obtained for colchicine with Succinyl-γ-CD and Sulfated-γ-CD, respectively. An opposite enantiomeric migration order was observed with these two CDs being S-colchicine the first-migrating enantiomer with Succinyl-γ-CD and the second-migrating enantiomer with Sulfated-γ-CD. H NMR experiments showed a 1:1 stoichiometry for the enantiomer-CD complexes in both cases. However, the apparent and averaged equilibrium constants for the enantiomer-CD complexes could be calculated only for Succinyl-γ-CD. The developed methods were applied to the analysis of pharmaceutical formulations but only the use of Succinyl-γ-CD enabled to detect a 0.1% of enantiomeric impurity in colchicine formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Colchicine-protein interactions revealed by transient absorption spectroscopy after in situ photoisomerization to lumicolchicines

    Science.gov (United States)

    Bartovský, Pavel; Tormos, Rosa; Miranda, Miguel A.

    2009-10-01

    Irradiation of colchicine (COL) inside serum albumins (SAs) at 350 nm, results in an efficient isomerization to β- and γ-lumicolchicines (LCs). Laser flash photolysis of pre-irradiated COL/SA complexes leads to detection of long-lived LC-derived triplet excited states ( λmax = 370 and 600 nm, τT > 10 μs).

  18. Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

    Science.gov (United States)

    Morel, N; Bonjour, M; Le Guern, V; Le Jeunne, C; Mouthon, L; Piette, J-C; Costedoat-Chalumeau, N

    2015-12-01

    Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up. © The Author(s) 2015.

  19. Polygamain, a New Microtubule Depolymerizing Agent That Occupies a Unique Pharmacophore in the Colchicine Site

    Science.gov (United States)

    Hartley, R. M.; Peng, J.; Fest, G. A.; Dakshanamurthy, S.; Frantz, D. E.; Brown, M. L.

    2012-01-01

    Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant mitotic spindles that led to G2/M arrest. Polygamain has potent antiproliferative activities against a wide range of cancer cell lines, with an average IC50 of 52.7 nM. Clonogenic studies indicate that polygamain effectively inhibits PC-3 colony formation and has excellent cellular persistence after washout. In addition, polygamain is able to circumvent two clinically relevant mechanisms of drug resistance, the expression of P-glycoprotein and the βIII isotype of tubulin. Studies with purified tubulin show that polygamain inhibits the rate and extent of purified tubulin assembly and displaces colchicine, indicating a direct interaction of polygamain within the colchicine binding site on tubulin. Polygamain has structural similarities to podophyllotoxin, and molecular modeling simulations were conducted to identify the potential orientations of these compounds within the colchicine binding site. These studies suggest that the benzodioxole group of polygamain occupies space similar to the trimethoxyphenyl group of podophyllotoxin but with distinct interactions within the hydrophobic pocket. Our results identify polygamain as a new microtubule destabilizer that seems to occupy a unique pharmacophore within the colchicine site of tubulin. This new pharmacophore will be used to design new colchicine site compounds that might provide advantages over the current agents. PMID:22169850

  20. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2015-10-01

    Full Text Available Objective To observe the clinical effect of small dose of colchicine combined with glucocorticoid for acute gouty arthritis. Methods Ninety-two patients with acute gouty arthritis were equally and randomly divided into small doses of colchicine combined with dexamethasone treatment group (treatment group and conventional large dose colchicine treatment group (control group between January 2009 and December 2013. The articular lesion scoring and clinical efficacy evaluation were performed at 3, 6, 12, 24, 48, and 72h after treatment. Erythrocyte sedimentation rate (ESR, white blood cells, hepatorenal function and glomerular filtration rate (GFR were determined before and 72h after treatment respectively. The gastrointestinal adverse events and recurrence rate were observed within one month after treatment. Results The articular lesion scores were significantly decreased at 6, 12, 48, and 72h after treatment in treatment group compared with control group (P0.05. Serum uric acid, glutamic-pyruvic transaminase in serum (SGPT, and GFR did not show any change before and 72h after the treatment, and there was also no significant difference between groups (P>0.05. The incidence of gastrointestinal adverse events were obviously higher in control group (76.1% compared with that of the treatment group (P<0.05, and the differences was statistically significant. There was no statistical difference in recurrence rate between the control group and treatment group after a follow-up of one month. Conclusions Compared with conventional large dose colchicine, small dose of colchicine combined with dexamethasone can more rapidly and effectively control acute gouty arthritis, with good tolerability and safety, thus being worthy of popularization clinically. DOI: 10.11855/j.issn.0577-7402.2015.08.10

  1. Enhanced stability of microtubules contributes in the development of colchicine resistance in MCF-7 cells.

    Science.gov (United States)

    Rai, Ankit; Kapoor, Sonia; Naaz, Afsana; Kumar Santra, Manas; Panda, Dulal

    2017-05-15

    Understanding the mechanism of resistance to tubulin-targeted anticancer drugs is important for improved chemotherapy. In this work, a colchicine-resistant MCF-7 cell line (MCF-7 Col30 ) was generated by the gradual increment of colchicine treatment and the MCF-7 Col30 showed ∼8-fold resistance towards colchicine. MCF-7 Col30 cells showed ∼2.5-fold resistance against microtubule depolymerizing agents, vinblastine, and nocodazole. In contrast, it displayed more sensitivity towards paclitaxel, a microtubule-polymerizing agent. MCF-7 and MCF-7 Col30 cells showed similar sensitivity towards cisplatin. Further, the level of P-glycoprotein did not increase in MCF-7 Col30 cells. MCF-7 Col30 cells resisted the microtubule depolymerizing effects of colchicine. The time-lapse imaging of individual microtubules in live cells showed that the dynamics of microtubules in MCF-7 Col30 cells was suppressed as compared to the parent MCF-7 cells. The levels of tubulin acetylation and glutamylation increased in MCF-7 Col30 cells than the parent MCF-7 cells suggesting that microtubules are stabilized in MCF-7 Col30 cells. Interestingly, the level of βIII tubulin was increased by 2.3 folds whereas that of βII and βIV tubulin was decreased by 55 and 150%, respectively in MCF-7 Col30 cells. The results suggested that the changes in the level of β-tubulin isoforms and the post-translational modifications of microtubules altered the stability and dynamics of microtubules and contributed to the development of colchicine-resistance in MCF-7 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats.

    Science.gov (United States)

    Atasever, Ayhan; Yaman, Duygu

    2014-10-01

    This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl4) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200-250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl4 (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl4 as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl4. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl4 induced acute hepatic damage. Copyright © 2014 Elsevier GmbH. All rights reserved.

  3. Ring accelerators

    International Nuclear Information System (INIS)

    Gisler, G.; Faehl, R.

    1983-01-01

    We present two-dimensional simulations in (r-z) and r-theta) cylinderical geometries of imploding-liner-driven accelerators of rings of charged particles. We address issues of azimuthal and longitudinal stability of the rings. We discuss self-trapping designs in which beam injection and extraction is aided by means of external cusp fields. Our simulations are done with the 2-1/2-D particle-in-cell plasma simulation code CLINER, which combines collisionless, electromagnetic PIC capabilities with a quasi-MHD finite element package

  4. Topological rings

    CERN Document Server

    Warner, S

    1993-01-01

    This text brings the reader to the frontiers of current research in topological rings. The exercises illustrate many results and theorems while a comprehensive bibliography is also included. The book is aimed at those readers acquainted with some very basic point-set topology and algebra, as normally presented in semester courses at the beginning graduate level or even at the advanced undergraduate level. Familiarity with Hausdorff, metric, compact and locally compact spaces and basic properties of continuous functions, also with groups, rings, fields, vector spaces and modules, and with Zorn''s Lemma, is also expected.

  5. Effect of ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Trial.

    Science.gov (United States)

    Tabbalat, Ramzi A; Hamad, Nidal M; Alhaddad, Imad A; Hammoudeh, Ayman; Akasheh, Bassam F; Khader, Yousef

    2016-08-01

    Atrial fibrillation (AF) is a common arrhythmia in patients undergoing cardiac surgery and may result in significant morbidity and increased hospital stay. This study was conducted to determine if colchicine administered preoperatively to patients undergoing cardiac surgery and continued during hospitalization is effective in reducing the incidence of postoperative AF. In this multicenter prospective randomized open-label study, consecutive patients with no history of AF and scheduled to undergo elective cardiac surgery (n = 360) were randomized to colchicine (n = 179) or no-colchicine (n = 181). Main exclusion criteria were history of AF or supraventricular arrhythmias or absence of sinus rhythm at enrolment, and contraindications to colchicine. Colchicine was orally administered 12 to 24 hours preoperatively and continued until hospital discharge. The primary efficacy end point was documented AF lasting more than 5 minutes. Safety end point was colchicine adverse effects. In-hospital mortality was 3.3%. The primary end point of AF occurred in 63 patients (17.5%): 26 (14.5%) in the colchicine group and 37 (20.5%) in the no-colchicine group (relative risk reduction 29.3% [P = .14]). Diarrhea occurred in 54 patients, 44 (24.6%) on colchicine and 10 (5.5%) on no-colchicine (P colchicine in 23 (52%) of the 44 patients. Colchicine administered preoperatively to patients undergoing cardiac surgery and continued until hospital discharge failed to significantly reduce the incidence of early postoperative AF. Diarrhea was the most common adverse effect of colchicine leading to its discontinuation in more than half of the patients with this adverse effect. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Ring interferometry

    CERN Document Server

    Malykin, Grigorii B; Zhurov, Alexei

    2013-01-01

    This monograph is devoted to the creation of a comprehensive formalism for quantitative description of polarized modes' linear interaction in modern single-mode optic fibers. The theory of random connections between polarized modes, developed in the monograph, allows calculations of the zero shift deviations for a fiber ring interferometer. The monograph addresses also the

  7. COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.

    Science.gov (United States)

    Akodad, Mariama; Lattuca, Benoît; Nagot, Nicolas; Georgescu, Vera; Buisson, Mathilde; Cristol, Jean-Paul; Leclercq, Florence; Macia, Jean-Christophe; Gervasoni, Richard; Cung, Thien-Tri; Cade, Stéphane; Cransac, Frédéric; Labour, Jessica; Dupuy, Anne-Marie; Roubille, François

    Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context. To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI). All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization. Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79). In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular colchicine injection.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Rupsa; Sanyal, Moumita; Guha, Debjani; Ghosh, Tusharkanti

    2016-01-01

    Colchicine induces neurodegeneration, but the extent of neurodegeneration in different areas of the brain in relation to neuroinflammation remains unclear. Such information may be useful to allow for the development of a model to compare colchicine-induced neurodegeneration with other neurodegenerative diseases such as Alzheimer's Disease (AD). The present study was designed to investigate the extent of neurodegeneration along with neuroinflammation in different areas of the brain, e.g. frontal cortex, parietal cortex, occipital cortex, corpus striatum, amygdala and hippocampus, in rats along with memory impairment 21 days after a single intracerebroventricular (icv) injection of colchicine. Memory parameters were measured before and after icv colchicine injection in all test groups of rats (control, sham-operated, colchicine-injected [ICIR] rats). On Day 21 post-injection, rats from all groups were anesthesized and tissues from the various brain areas were collected for assessment of biomarkers of neuroinflammation (i.e. levels of ROS, nitrite and proinflammatory cytokines TNFα and IL-1β) and neurodegeneration (assessed histologically). The single injection of colchicine resulted in impaired memory and neurodegeneration (significant presence of plaques, Nissl granule chromatolysis) in various brain areas (frontal cortex, amygdala, parietal cortex, corpus striatum), with maximum severity in the hippocampus. While IL-1β, TNFα, ROS and nitrite levels were altered in different brain areas in the ICIR rats, these parameters had their greatest change in the hippocampus. This study showed that icv injection of colchicine caused strong neurodegeneration and neuroinflammation in the hippocampus of rats and the increases in neurodegeneration were corroborated with those of neuroinflammation at the site. The present study also showed that the extent of neurodegeneration and neuroinflammation in different brain areas of the colchicine-injected rats were AD-like and

  9. Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model.

    Science.gov (United States)

    Akodad, Mariama; Fauconnier, Jérémy; Sicard, Pierre; Huet, Fabien; Blandel, Florence; Bourret, Annick; de Santa Barbara, Pascal; Aguilhon, Sylvain; LeGall, Marion; Hugon, Gérald; Lacampagne, Alain; Roubille, François

    2017-08-01

    Inflammation is deeply involved in the pathophysiology of ischemia-reperfusion (I/R) lesions and ventricular remodeling due to an acute myocardial infarction (AMI). Colchicine as a pleiotropic anti-inflammatory molecule may exert cardioprotective effects under acute ischemia. Here, we aimed to evaluate the impact of colchicine on reperfusion injury in a mouse model. Myocardial ischemia/reperfusion (I/R) injury was induced in C57BL/6 male mice, after 45min ligation of the left coronary artery followed by reperfusion. 400μg/kg of colchicine or the vehicle was administrated intraperitoneally (i.p.) 25min before the reperfusion (blinded administration). Mice were sacrificed at 24h after the acute myocardial ischemia (AMI) and the infarct size was determined. Circulating level of troponin and cytokines profile were assessed 4h after the AMI. An echocardiography was performed in a follow-up group mice, 48h and 8weeks after the AMI. The infarct size was reduced in colchicine treated mice (39.8±3.5% versus 52.9±3.2%, pcolchicine treated mice (7015.7±1423.7pg/mL, n=5 vs 30,723.7±7959.9pg/mL in the placebo group, n=6; pColchicine group (24.51±3.13% vs 11.38±2.46%, p=0.03). In the follow-up group mice (n=8), there were no differences between mice treated with placebo (n=9) and mice treated with colchicine (n=9) regarding to cardiac remodeling parameters but outflow approximated by the ITV was higher in the colchicine group. In conclusion, colchicine allowed a significant reduction of infarct size in mice, improves hemodynamic parameters and decrease cardiac fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis.

    Science.gov (United States)

    Hemkens, Lars G; Ewald, Hannah; Gloy, Viktoria L; Arpagaus, Armon; Olu, Kelechi K; Nidorf, Mark; Glinz, Dominik; Nordmann, Alain J; Briel, Matthias

    2016-04-01

    Colchicine is an old anti-inflammatory drug that has shown substantial cardiovascular benefits in recent trials. We systematically reviewed cardiovascular benefits and harms of colchicine in any population and specifically in patients with high cardiovascular risk. We evaluated randomised controlled trials comparing colchicine over at least 6 months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction and adverse events. Cardiovascular mortality was a secondary outcome. We included 39 trials with 4992 patients. The quality of evidence for mortality outcomes and myocardial infarction was moderate but lower for adverse events. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; I(2)=27%; 30 trials). Cardiovascular mortality was reduced in some but not all meta-analytical models (random-effects RR 0.34, 0.09 to 1.21, I(2)=9%; Peto's OR 0.24, 0.09 to 0.64, I(2)=15%; Mantel-Haenszel fixed-effect RR 0.20, 0.06 to 0.68, I(2)=0%; 7 trials). The risk for myocardial infarction was reduced (RR 0.20, 0.07 to 0.57; 2 trials). There was no effect on total adverse events (RR 1.52, 0.93 to 2.46, I(2)=45%; 11 trials) but gastrointestinal intolerance was increased (RR 1.83, 1.03 to 3.26, I(2)=74%; 11 trials). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects in high cardiovascular risk populations were similar (4 trials; 1230 patients). We found no evidence supporting colchicine doses above 1 mg/day. Colchicine may have substantial cardiovascular benefits; however, there is sufficient uncertainty about its benefit and harm to indicate the need for large-scale trials to further evaluate this inexpensive, promising treatment in cardiovascular disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Effect of oral Colchicine on Peripapillary retinal nerve fiber layer thickness in patients with familial Mediterranean fever.

    Science.gov (United States)

    Tanyıldız, Burak; Tezcan, Mehmet Engin; Kandemir, Baran; Günaydın, Nesrin Tutaş; Göktaş, Eren; Tangılntız, Aise; Arsan, Aysu Karatay

    2018-02-05

    The purpose of this study is to investigate whether oral colchicine has an effect on peripapillary retinal nerve fiber layer (pRNFL) thickness of familial Mediterranean fever (FMF) patients. We conducted a cross sectional study by comparing pRNFL thickness of FMF patients on colchicine (treated group), newly diagnosed colchicine naïve FMF patients (untreated group) and healthy controls. The study included 66 FMF patients and 32 healthy control subjects. Treated FMF patients were grouped according to colchicine use, duration of use and dosage. pRNFL thickness of the patients and controls were measured by using optical coherence tomography and the measurements were compared. No statistically significant difference was found between the pRNFL thickness in untreated group, treated group and the healthy control group (all p > 0.05). No statistically significant difference was found between pRNFL thickness in the healthy control group and FMF patients grouped according to duration or dosage of colchicine use (all p > 0.05). According to our study, FMF and oral colchicine use had no statistically significant effect on pRNFL thickness.

  12. Remnant motility of macrophages treated with cytochalasin B in the presence of colchicine

    Energy Technology Data Exchange (ETDEWEB)

    Bhisey, A.N. (Tata Memorial Centre, Bombay); Freed, J.J.

    1975-01-01

    It has previously been observed that mouse peritoneal macrophages cultured for 48 h and treated with colchicine to depolymerize cytoplasmic microtubules become ameboid and cease to migrate by gliding on the substratum. It has now been found that when such cells were further exposed to both colchicine and cytochalasin B, the induced ameboid movements were reversibly inhibited. Cells treated concomitantly with both drugs did not become motionless, but exhibited a remnant motility that took the form of zeiosis (blebbing). The zeiotic blebs contained ribosomes and fibrous material, but lacked organized microfilament arrays and rarely included other cytoplasmic organelles. Zeiosis appears to be a form of surface movement independent both of cytoplasmic microtubules and of the cytochalasin-sensitive contractile system. These observations imply an additional mechanism that can reversibly alter the from of the cell.

  13. Effect of irradiation and colchicine on callus and somatic embryo formation in cassava (Manihot esculenta Crantz)

    International Nuclear Information System (INIS)

    Dzimega, D. A.

    2012-06-01

    A study was conducted to assess the mutagenic effect of gamma radiation on sprouting and height in four local cassava accessions. The four cassava accessions were assessed for their callus induction and somatic embryo formation ability from leaf lobes from gamma irradiated stakes as well as colchicine treated leaf lobes on different concentrations of plant growth regulators, incorporated into Murashige and skoog, (1962) (MS) basal medium. The cassava accessions were irradiated at 0, 32, 35, 45 and 50 Gy and planted in pots filled with loamy soil. The height of the shoots was measured with rule after sprouting. The leaf lobes were collected from the shoots and cultured on MS medium supplemented with 8 mg/l 2, 4-D and 16 mg/l Picloram. Another set of leaf lobes were treated with 0.0, 0.05, 0.1, 0.2, 0.25 g/l colchicine for one hour and thereafter culture on MS medium supplemented with 8 mg/l 2,4-D and 16 mg/l Picloram as described above. Callus induction from leaf lobes in 45 and 50 Gy were significantly (p≤0.05) affected by the irradiation. On the other hand, Callus induction from leaf lobes in 0.1-0.25 g/l colchicine were significantly (p≤0.05) affected by the mutagenic treatment whereas callus induced from leaf lobes in 0.05 g/l colchicine was not significantly (p≤0.05) affected. Callus induced on 8 mg/l 2, 4-D and 16 mg/l picloram gave the best response in Ankrah and all control tested while Tomfa recorded the least. Colchicine at a concentration of 0.05 g/l and radiation dose of 32 Gy treatments gave the best response of callusing. Callus induction decreased with increasing colchicine concentration and gamma irradiation. Callus derived from irradiated and colchicine leaf lobes appeared soft but friable and tiny, compact, respectively, predominately with creamy to brown colouration. Calli obtained were sub-cultures on embryo regeneration medium consisting of MS supplemented with 0.01mg/1 NAA and o.1 mg/1 BAP. There was no plantlet regeneration. Instead

  14. [A case of colchicine-responsive Mollaret's meningitis with MEFV gene mutation].

    Science.gov (United States)

    Kinohshita, Tomomi; Matsushima, Akira; Satoh, Shunichi; Hoshi, Kenichi; Kishida, Dai; Yahikozawa, Hiroyuki

    2014-01-01

    A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinal fluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF, neuro-Behçet's disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases.

  15. Treatment with aspirin, NSAID, corticosteroids, and colchicine in acute and recurrent pericarditis.

    Science.gov (United States)

    Imazio, Massimo; Adler, Yehuda

    2013-05-01

    Empiric anti-inflammatory therapy for acute and recurrent pericarditis is warranted for viral and idiopathic cases that represent most cases of pericarditis in developed countries. For specific uncomplicated etiologies, such as systemic autoimmune diseases and postpericardiotomy syndromes, the same drugs are also indicated. Aspirin and non-steroidal anti-inflammatory drugs (NSAID) are mainstay of therapy with the possible adjunct of colchicine, especially for recurrences. Corticosteroids are a second choice for difficult cases requiring multi-drug therapies and specific medical conditions (i.e., specific cases with systemic autoimmune diseases, postpericardiotomy syndrome, and pregnancy). Medical therapy of pericarditis should be individualized as much as possible providing the attack dose every 8 h to ensure full daily control of symptoms and till remission and C-reactive protein normalization, and then tapering should be considered. The present paper will review current evidence for the treatment of acute and recurrent pericarditis with aspirin, NSAID, corticosteroids, and colchicine.

  16. Successful Treatment of Scleredema Diabeticorum by Combining Local PUVA and Colchicine: A Case Report

    Directory of Open Access Journals (Sweden)

    Chayada Kokpol

    2012-11-01

    Full Text Available Scleredema is a rare condition of unknown pathogenesis. It is classically divided into three types, based on its association with postinfection (usually streptococcal, monoclonal gammopathy and diabetes mellitus (scleredema diabeticorum. Scleredema diabeticorum often has a subtle onset, persistent involvement and is refractory to therapies. Numerous therapies have been tried, with mixed and inconsistent results. We report herein a case of scleredema diabeticorum that was successfully treated by combining local PUVA with colchicine.

  17. Colchicine therapy in amyloidosis related with plasmacytic castleman disease presenting with nephrotic syndrome

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    Saime Paydas

    2015-01-01

    Full Text Available Castleman disease (CD is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery.

  18. Injection of colchicine intra-hippocampal cortical area 1 enhances novelty seeking behavior

    Science.gov (United States)

    Karami, Manizheh; Riahi, Nosaibeh; Nadoushan, Mohammad Reza Jalali

    2013-01-01

    Objective: Colchicine, a potent neurotoxin derived of plant has been recently identified as a degenerative toxin of small pyramidal cells in the hippocampal cortical area 1 (CA1). In this study, the effect of the alkaloid intra hippocampal CA1 on the novelty seeking behavior in the conditioning task was measured. Materials and Methods: Injections of colchicine (1-75 μg/rat, intra-CA1) were performed in cannulated male Wistar rats while being settled in the stereotaxic apparatus. Control group was solely injected saline (1 μl/rat, intra-CA1). One week later, after recovery, all the animals passed the novelty seeking paradigm using an unbiased conditioning task. They were habituated with the conditioned place preference (CPP) apparatus on day 1. Then they were confined in one part of the CPP box for 3 more days. Finally, the animals were tested in the last day. To evaluate, the possible cell injury effect of the toxin on the pyramidal cells of the CA1 both the motivational staying signal in the parts of the box and the non-motivational locomotive signs of the rats were measured. Results: Based on the present study, the alkaloid caused significant novelty seeking behavior at higher doses. It also affected the compartment entering behavior in the colchicine received group. However, the alkaloid did not show the significant effect on sniffing, rearing or grooming in the rats. Conclusion: Injection of colchicine intra-CA1 may impair the neuronal transmission of motivational information by the pyramidal cells in the dorsal hippocampus. PMID:23833372

  19. Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome.

    Science.gov (United States)

    Butbul Aviel, Yonatan; Tatour, Sameh; Gershoni Baruch, Ruth; Brik, Riva

    2016-02-01

    To evaluate the efficacy of colchicine in reducing the frequency of attacks in patients with PFAPA. We conducted a 6-month open label, randomized, controlled study among patients with PFAPA who attend the Pediatric Rheumatology Clinic at the Rambam Medical Center in Israel. A total of 18 patients aged4 -11 years (males:females ratio = 11:7) were randomized into a control group (I, 10 children) and a study group (II, 8 children). Group I was followed for 6 months without any intervention, and group II was initially followed for 3 months and was thereafter treated with colchicine for 3 additional months, according to standard regimen. During the 6-month period of the study the patients and their physician recorded all the episodes of PFAPA in a constructed log. DNA analyses for the 5 common FMF mutations in Israel were performed in 17 out of the 18 patients. The number of episodes during the first 3 months was similar in both groups (group I 3.2 ± 1.5, group II 4.9 ± 2.3; p ≤ 0.12). Group II had significantly less PFAPA attacks in the second period while on colchicine therapy (4.9 ± 2.3 vs. 1.6 ± 1.2; p ≤ 0.01), in opposition to group I, where no difference in the number of attacks was noted between the first and second period of follow-up (3.2 ± 1.5 vs. 2.7 ± 1.5; p = 0.33). Of the 17 patients tested, 8 were carriers for FMF mutations (2 in group I and 6 in group II). Colchicine prophylaxis seems to be effective in reducing the number of attacks in PFAPA. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay

    Science.gov (United States)

    Seiliez, Iban; Belghit, Ikram; Gao, Yujie; Skiba-Cassy, Sandrine; Dias, Karine; Cluzeaud, Marianne; Rémond, Didier; Hafnaoui, Nordine; Salin, Bénédicte; Camougrand, Nadine; Panserat, Stéphane

    2016-01-01

    ABSTRACT Monitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of β-oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo “autophagometer.” PMID:26902586

  1. Lithium + Colchicine: A Potential Strategy to Reduce Pro-inflammatory Effects of Lithium Treatment.

    Science.gov (United States)

    Mooney, John J; Brady, Roscoe O

    2018-02-01

    Rosenblat and McIntyre (Acta Psychiatr Scand. 2015;132: 180-191) propose that immune disorders are important mediators between bipolar disorders and medical comorbidities. Rosenblat et al (Bipolar Disord. 2016;18:89-101) present a meta-analysis showing that adjunctive anti-inflammatory agents could evoke moderate antidepressant responses in bipolar disorders. We propose using the anti-inflammatory drug colchicine to improve the long-term safety and efficacy of lithium treatment for bipolar disorders. This report is based on searches of the PubMed and Web of Science databases. Bipolar disorders are associated with significant medical comorbidities such as hypertension, overweight/obesity, diabetes mellitus, metabolic syndrome, and arteriosclerosis, accompanied by enhanced release of pro-inflammatory markers during changes in mood state. During lithium therapy, granulocyte-colony stimulating factor, CD34+ hematopoietic stem/progenitor cells, and neutrophil elastase enter the circulation with activated neutrophils to promote the extravascular migration of activated neutrophils and enhance tissue inflammation. Concurrent treatment with lithium and low-dose colchicine could facilitate the responsiveness of bipolar patients to lithium by reducing leukocyte tissue emigration, the release of neutrophil elastase, and the release of leukocyte pro-inflammatory cytokines such as IL-1β that are regulated by the NLRP3 inflammasome assembly complex. Concurrent therapy with lithium and low-dose colchicine could reduce complications involving leukocyte-mediated inflammatory states in bipolar patients and promote patient acceptance and responsiveness to lithium therapy.

  2. Colchicine protects rat skeletal muscle from ischemia/reperfusion injury by suppressing oxidative stress and inflammation

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    Liangrong Wang

    2016-06-01

    Full Text Available Objective(s: Neutrophils play an important role in ischemia/reperfusion (IR induced skeletal muscle injury. Microtubules are required for neutrophil activation in response to various stimuli. This study aimed to investigate the effects of colchicine, a microtubule-disrupting agent, on skeletal muscle IR injury in a rat hindlimb ischemia model. Materials and Methods: Twenty-one Sprague-Dawley rats were randomly allocated into three groups: IR group, colchicine treated-IR (CO group and sham operation (SM group. Rats of both the IR and CO groups were subjected to 3 hr of ischemia by clamping the right femoral artery followed by 2 hr of reperfusion. Colchicine (1 mg/kg was administrated intraperitoneally prior to hindlimb ischemia in the CO group. After 2 hr of reperfusion, we measured superoxide dismutase (SOD and myeloperoxidase (MPO activities, and malondialdehyde (MDA, tumor necrosis factor (TNF-α and interleukin (IL-1β levels in the muscle samples. Plasma creatinine kinase (CK and lactate dehydrogenase (LDH levels were measured. We also evaluated the histological damage score and wet/dry weight (W/D ratio. Results: The histological damage score, W/D ratio, MPO activity, MDA, TNF-α and IL-1β levels in muscle tissues were significantly increased, SOD activity was decreased, and plasma CK and LDH levels were remarkably elevated in both the IR and CO groups compared to the SM group (P

  3. A prospective investigation into the effect of colchicine on tuberculous pericarditis.

    Science.gov (United States)

    Liebenberg, Jurgens Jacobus; Dold, Catherine Jane; Olivier, Lourens Rasmus

    Tuberculous (TB) pericarditis carries significant mortality and morbidity rates, not only during the primary infection, but also as part of the granulomatous scar-forming fibrocalcific constrictive pericarditis so commonly associated with this disease. Numerous therapies have previously been investigated as adjuvant strategies in the prevention of pericardial constriction. Colchicine is well described in the treatment of various aetiologies of pericarditis. The aim of this research was to investigate the merit for the use of colchicine in the management of tuberculous pericarditis, specifically to prevent constrictive pericarditis. This pilot study was designed as a prospective, double-blinded, randomised, control cohort study and was conducted at a secondary level hospital in the Northern Cape of South Africa between August 2013 and December 2015. Patients with a probable or definite diagnosis of TB pericarditis were included (n = 33). Study participants with pericardial effusions amenable to pericardiocentesis underwent aspiration until dryness. All patients were treated with standard TB treatment and corticosteroids in accordance with the South African Tuberculosis Treatment Guidelines. Patients were randomised to an intervention and control group using a web-based computer system that ensured assignment concealment. The intervention group received colchicine 1.0 mg per day for six weeks and the control group received a placebo for the same period. Patients were followed up with serial echocardiography for 16 weeks. The primary outcome assessed was the development of pericardial constriction. Upon completion of the research period, the blinding was unveiled and data were presented for statistical analysis. TB pericarditis was found exclusively in HIV-positive individuals. The incidence of pericardial constriction in our cohort was 23.8%. No demonstrable benefit with the use of colchicine was found in terms of prevention of pericardial constriction (p = 0

  4. A prospective investigation into the effect of colchicine on tuberculous pericarditis

    Science.gov (United States)

    Liebenberg, Jurgens; Dold, Catherine Jane; Olivier, Lourens Rasmus

    2016-01-01

    Summary Introduction Tuberculous (TB) pericarditis carries significant mortality and morbidity rates, not only during the primary infection, but also as part of the granulomatous scar-forming fibrocalcific constrictive pericarditis so commonly associated with this disease. Numerous therapies have previously been investigated as adjuvant strategies in the prevention of pericardial constriction. Colchicine is well described in the treatment of various aetiologies of pericarditis. The aim of this research was to investigate the merit for the use of colchicine in the management of tuberculous pericarditis, specifically to prevent constrictive pericarditis. Methods This pilot study was designed as a prospective, double-blinded, randomised, control cohort study and was conducted at a secondary level hospital in the Northern Cape of South Africa between August 2013 and December 2015. Patients with a probable or definite diagnosis of TB pericarditis were included (n = 33). Study participants with pericardial effusions amenable to pericardiocentesis underwent aspiration until dryness. All patients were treated with standard TB treatment and corticosteroids in accordance with the South African Tuberculosis Treatment Guidelines. Patients were randomised to an intervention and control group using a webbased computer system that ensured assignment concealment. The intervention group received colchicine 1.0 mg per day for six weeks and the control group received a placebo for the same period. Patients were followed up with serial echocardiography for 16 weeks. The primary outcome assessed was the development of pericardial constriction. Upon completion of the research period, the blinding was unveiled and data were presented for statistical analysis. Results TB pericarditis was found exclusively in HIV-positive individuals. The incidence of pericardial constriction in our cohort was 23.8%. No demonstrable benefit with the use of colchicine was found in terms of prevention of

  5. Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects.

    Science.gov (United States)

    Shah, Binita; Allen, Nicole; Harchandani, Bhisham; Pillinger, Michael; Katz, Stuart; Sedlis, Steven P; Echagarruga, Christina; Samuels, Svetlana Krasnokutsky; Morina, Pajazit; Singh, Prabhjot; Karotkin, Liza; Berger, Jeffrey S

    2016-02-01

    The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

  6. In vitro colchicine-induced polyploid plantlet production and regeneration from leaf explants of the diploid pear (Pyrus communis L.) cultivar, 'Fertility'

    Science.gov (United States)

    Polyploid plantlets, including triploid, tetraploid and other polyploids, were induced from in vitro leaves of a European pear (Pyrus communis L.) cultivar 'Fertility' by a colchicine treatment. In vitro leaves were incubated in 0.4% colchicine solution for 24, 48 or 72 h, and transferred to an adv...

  7. Comparative Analyses of the β-Tubulin Gene and Molecular Modeling Reveal Molecular Insight into the Colchicine Resistance in Kinetoplastids Organisms

    Science.gov (United States)

    Luis, Luis; Serrano, María Luisa; Hidalgo, Mariana; Mendoza-León, Alexis

    2013-01-01

    Differential susceptibility to microtubule agents has been demonstrated between mammalian cells and kinetoplastid organisms such as Leishmania spp. and Trypanosoma spp. The aims of this study were to identify and characterize the architecture of the putative colchicine binding site of Leishmania spp. and investigate the molecular basis of colchicine resistance. We cloned and sequenced the β-tubulin gene of Leishmania (Viannia) guyanensis and established the theoretical 3D model of the protein, using the crystallographic structure of the bovine protein as template. We identified mutations on the Leishmania   β-tubulin gene sequences on regions related to the putative colchicine-binding pocket, which generate amino acid substitutions and changes in the topology of this region, blocking the access of colchicine. The same mutations were found in the β-tubulin sequence of kinetoplastid organisms such as Trypanosoma cruzi, T. brucei, and T. evansi. Using molecular modelling approaches, we demonstrated that conformational changes include an elongation and torsion of an α-helix structure and displacement to the inside of the pocket of one β-sheet that hinders access of colchicine. We propose that kinetoplastid organisms show resistance to colchicine due to amino acids substitutions that generate structural changes in the putative colchicine-binding domain, which prevent colchicine access. PMID:24083244

  8. Stimulation effects of γ-irradiation combined with colchicine on callus formation and green plant regeneration in rice anther culture

    International Nuclear Information System (INIS)

    Jin Wei; Chen Qiufang; Wang Cailian; Lu Yimei

    1999-09-01

    The ability of callus formation and green plant regeneration was very different for various rice types and varieties in rice anther culture. It was quite effective that rice anthers were irradiated with 10-40 Gy of γ-rays after 30 d incubation on induction medium and calli were treated on differentiation medium contained 10-75 mg/L of colchicine for increase of callus formation and green plant regeneration. Among these treatments, 10 Gy of γ-rats was the best for callus formation, and 20 Gy of γ-rays or 30 mg/L of colchicine was the most favourable for green plant regeneration. The simulation effect of 20 Gy of γ-irradiation combined with 30 mg/L of colchicine on green plant regeneration was much better than that of their separate use in rice anther culture

  9. The Role of Colchicine in Pericarditis--A Systematic Review and Meta-analysis of Randomised Trials.

    Science.gov (United States)

    Raval, Jwalant; Nagaraja, Vinayak; Eslick, Guy D; Denniss, A Robert

    2015-07-01

    Colchicine has been used in diverse clinical settings. Primary idiopathic pericarditis is complicated by recurrence in 15 to 30% of cases. Aspirin, non-steroidal anti-inflammatory drugs, colchicine and steroids are the commonly prescribed medications. We synthesised the available evidence from the randomised trials to assess the efficacy and safety of colchicine in primary and recurrent pericarditis. A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate an odds ratio (OR) and 95% confidence interval (95% CI). Seven randomised trials comprising 1275 patients met full criteria for analysis. Two open label randomised controlled trials and five double-blind randomised controlled trials were included. Colchicine was useful in reducing the incidence of primary pericarditis (OR: 0.38, 95% CI: 0.22- 0.65) as well as recurrent pericarditis (OR: 0.31, 95% CI: 0.22-0.44). The most common side-effects were related to the gastrointestinal system and no severe adverse events were observed. Colchicine cessation either by patient or physician was similar in both groups (OR: 1.53, 95% CI: 0.86-2.71). Colchicine is effective in preventing both primary and recurrent episodes of pericarditis. The number needed to treat for preventing recurrent pericarditis was five. Gastrointestinal side-effects were the most common adverse events. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  10. Familial Mediterranean fever in children and adolescents: factors for colchicine dosage and predicting parameters for dose increase.

    Science.gov (United States)

    Knieper, Anne-Marie; Klotsche, Jens; Lainka, Elke; Berger, Thomas; Dressler, Frank; Jansson, Annette F; Rietschel, Christoph; Oommen, Prasad T; Berendes, Rainer; Niehues, Tim; Neudorf, Ulrich; Foell, Dirk; Wittkowski, Helmut; Kallinich, Tilmann

    2017-09-01

    The aim was to analyse factors influencing the individual colchicine dose in children with FMF, to evaluate the impact of dose adjustment on the clinical course and inflammation and to identify clinical parameters and biomarkers that predict dose increase in the near future. Data from 409 paediatric FMF patients (4566 visits) derived from the national auto-inflammatory diseases registry were analysed. Serum concentrations of S100 molecules were determined by ELISA. The age-dependent colchicine dose is influenced by the present genotype. The body surface area is the anthropometric parameter that correlates best with the applied dosages. Colchicine introduction and dose increase lead to significant reduction of clinical symptoms and inflammation. During established colchicine therapy, an increase of one single biomarker increases the likelihood of a dose increment in the next 12 months with a factor of 1.62-1.94. A combination of biomarkers including S100 molecules increases this odds ratio up to 4.66 when analysing all patients and up to 7.27 when analysing patients with a high risk of severe disease. Colchicine therapy is currently guided mainly by the occurrence of clinical symptoms and serological inflammation. Other factors, such as the genotype, the body surface area and biomarkers, will help to manage colchicine therapy in a more individualized fashion. The additional analysis of S100 molecules as sensitive biomarkers will help to identify patients at risk for dose increases in the near future. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  11. Colchicine induces apoptosis in HT‑29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways.

    Science.gov (United States)

    Huang, Zhen; Xu, Ye; Peng, Wei

    2015-10-01

    Colchicine is a natural compound, which belongs to the botanical family Colchicaceae and prevents growth of cancer cells via antimitotic activity by interacting with microtubules. Although numerous studies have demonstrated that the effect of colchicine on cell apoptosis is mediated by the activation of caspase‑3, the signaling pathways involved in the process remain unknown. In the current study, evidence is presented regarding the missing information using HT‑29 human colon cancer cells. The effect of colchicine on apoptosis in HT‑29 cells and the apoptosis‑associated signaling pathways were determined using various methods, including cell viability assay, Annexin V/propidium idodide (PI) binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential (Δψm) assay, reactive oxygen species (ROS) assay and western blot analysis. Colchicine was observed to induce a dose‑dependent reduction in cell viability in HT‑29 cells and early apoptosis occurred when the cells were treated with 1 µg/ml colchicine. Furthermore, colchicine treatment induced a loss of Δψm, increased ROS production, activated caspase‑3, upregulated BAX expression and downregulated Bcl‑2 expression, which evidenced the colchicine activity on apoptosis, potentially by acting via the intrinsic apoptotic signaling pathway. Colchicine increased phosphorylation of p38, although not phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, which indicates that colchicine activates the p38 signaling pathway in order to induce cell apoptosis. Therefore, colchicine exhibited significant growth inhibition of the HT‑29 colon cancer cell line and induced apoptosis in the cells via the mitochondrial pathway, which is regulated by p38 signaling pathways.

  12. Uniparental disomy of chromosome 16 in offsprings of Familial Mediterranean Fever (FMF) patients treated with colchicine

    Energy Technology Data Exchange (ETDEWEB)

    Korenstein, A.; Avivi, L. [Tel-Avivi University (Israel); Ravia, Y. [Sheba Medical Center, Tel-Hashomer (Israel)

    1994-09-01

    Uniparental disomy (UPD), an altered mode of Mendelian inheritance, may reveal expression of recessive alleles due to the loss of heterozygosity, as well as imprinted genes. The mechanism causing UPD can be best elucidated in offsprings of individuals at high risk for chromosomal non-disjunction. Such individuals are Familial Mediterranean Fever (FMF) patients, who are routinely treated with the antimitotic agent colchicine, and, therefore, are expected to be at an increased risk for aneuploidy. A dominant mode of inheritance was observed in four FMF offsprings having one parent exhibiting the FMF phenotype (homozygote recessive) while the other was free of the mutant allele (as assumed from his ethnic background). Out of these, two exhibited UPD of chromosome 16, which carries the FMF gene, as judged from four different RFLP markers along this chromosome. Since in both case the UPD was of maternal origin, it is suggested that the colchicine-treated FMF mothers contributed two doses of chromosome 16, presumably due to meiotic non-disjunction, followed by a somatic loss of the paternal chromosome 16 in the embryo. The somatic chromosome loss is also assumed to be caused by the antimitotic drug since the mother continued to receive it during pregnancy. Whether the UPD arises from the colchicine treatment, from the high tendency of chromosome 16 to maternal non-disjunction or from both remains to be elucidated. Our results highlighted the importance of taking UPD into account when counseling individuals who are either treated with antimitotic agents or are carriers of recessive mutant alleles which are mapped to chromosomes prone to aneuploidy.

  13. Ringing phenomenon of the fiber ring resonator.

    Science.gov (United States)

    Ying, Diqing; Ma, Huilian; Jin, Zhonghe

    2007-08-01

    A resonator fiber-optic gyro (R-FOG) is a high-accuracy inertial rotation sensor based on the Sagnac effect. A fiber ring resonator is the core sensing element in the R-FOG. When the frequency of the fiber ring resonator input laser is swept linearly with time, ringing of the output resonance curve is observed. The output field of the fiber ring resonator is derived from the superposition of the light transmitted through the directional coupler directly and the multiple light components circulated in the fiber ring resonator when the frequency of the laser is swept. The amplitude and phase of the output field are analyzed, and it is found that the difference in time for different light components in the fiber ring resonator to reach a point of destructive interference causes the ringing phenomenon. Finally the ringing phenomenon is observed in experiments, and the experimental results agree with the theoretical analysis well.

  14. Induction of Tetraploid Male Sterile Tagetes erecta by Colchicine Treatment and Its Application for Interspecific Hybridization

    Directory of Open Access Journals (Sweden)

    Yanhong He

    2016-09-01

    Full Text Available Tagetes erecta is an annual multifunctional plant which can be cultivated under a broad range of climatic conditions. Polyploidization and interspecific hybridization are applied to facilitate breeding cultivars of T. erecta with improved ornamental qualities. Colchicine treatment to the germinating seeds was proved to be a useful tool for chromosome doubling of the male sterile two-type line ‘M525AB’, with the resulting frequency of polyploid seedlings ranging from 88.89% (following 0.05% w/v colchicine applied for a 3–6 h exposure period to a maximum of 100.00% (following 0.1% for 3–6 h, or 0.2% for 3 h. Morphological observation, stomatal size and density analysis, flow cytometric analysis and chromosome counting were conducted to identify the tetraploid plants. Distinctive morphological changes were observed in a notable proportion of polyploid plants. The colchicine-treated polyploid T. erecta plants showed dwarfed and more robust growth, thicker, larger and greener leaves, larger inflorescences and florets. The mutant plants identified through morphological observation all aligned as polyploid plants, thus morphological observation could be an effective method for the detection of polyploidy. The polyploid plants had significant larger stomata size over the abaxial leaf surface, whereas the density of stomata distribution was remarkably reduced. The survival rate of tetraploid cuttings (i.e. 38% was greatly reduced compared to that of diploid plants. The fertility of tetraploid plants was also decreased, as shown by cross-pollination yields. Interspecific hybridizations between colchicine-induced tetraploid plants of a male sterile T. erecta line and the naturally tetraploid fully fertile Tagetes patula species resulted in hybrid progeny. Most of these hybrids displayed the dwarfed growth stature and compact, larger-flower morphology which is the typical ideotype of herbaceous flowers. Thus, polyploidization may be employed

  15. ASSOCIATIVE RINGS SOLVED AS LIE RINGS

    Directory of Open Access Journals (Sweden)

    M. B. Smirnov

    2011-01-01

    Full Text Available The paper has proved that an associative ring which is solvable of a n- class as a Lie ring has a nilpotent ideal of the nilpotent class not more than 3×10n–2  and a corresponding quotient ring satisfies an identity [[x1, x2, [x3, x4

  16. Radical theory of rings

    CERN Document Server

    Gardner, JW

    2003-01-01

    Radical Theory of Rings distills the most noteworthy present-day theoretical topics, gives a unified account of the classical structure theorems for rings, and deepens understanding of key aspects of ring theory via ring and radical constructions. Assimilating radical theory's evolution in the decades since the last major work on rings and radicals was published, the authors deal with some distinctive features of the radical theory of nonassociative rings, associative rings with involution, and near-rings. Written in clear algebraic terms by globally acknowledged authorities, the presentation

  17. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation

    Science.gov (United States)

    Demidowich, Andrew P.; Davis, Angela I.; Dedhia, Nicket; Yanovski, Jack A.

    2016-01-01

    Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. PMID:27241260

  18. Stirling engine piston ring

    Science.gov (United States)

    Howarth, Roy B.

    1983-01-01

    A piston ring design for a Stirling engine wherein the contact pressure between the piston and the cylinder is maintained at a uniform level, independent of engine conditions through a balancing of the pressure exerted upon the ring's surface and thereby allowing the contact pressure on the ring to be predetermined through the use of a preloaded expander ring.

  19. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  20. Field performance of vegetative form traits of neopolyploids produced by in vitro colchicine treatment in Pyrus communis

    Science.gov (United States)

    The induction of polyploidy to improve agronomically and economically useful characters is a process commonly used in crop plants. Neopolyploids were obtained from pear diploid cultivar ‘Fertility’ by in vitro colchicine treatment. Different ploidy clones were rooted to be transferred to the field...

  1. Quantum-chemical, NMR, FT IR, and ESI MS studies of complexes of colchicine with Zn(II).

    Science.gov (United States)

    Jankowski, Wojciech; Kurek, Joanna; Barczyński, Piotr; Hoffmann, Marcin

    2017-04-01

    Colchicine is a tropolone alkaloid from Colchicinum autumnale. It shows antifibrotic, antimitotic, and anti-inflammatory activities, and is used to treat gout and Mediterranean fever. In this work, complexes of colchicine with zinc(II) nitrate were synthesized and investigated using DFT, 1 H and 13 C NMR, FT IR, and ESI MS. The counterpoise-corrected and uncorrected interaction energies of these complexes were calculated. We also calculated their 1 H, 13 C NMR, and IR spectra and compared them with the corresponding experimentally obtained data. According to the ESI MS mass spectra, colchicine forms stable complexes with zinc(II) nitrate that have various stoichiometries: 2:1, 1:1:1, and 2:1:1 with respect to colchichine, Zn(II), and nitrate ion. All of the complexes were investigated using the quantum theory of atoms in molecules (QTAIM). The calculated and the measured spectra showed differences before and after the complexation process. Calculated electron densities and bond critical points indicated the presence of bonds between the ligands and the central cation in the investigated complexes that satisfied the quantum theory of atoms in molecules. Graphical Abstract DFT, NMR, FT IR, ESI MS, QTAIM and puckering studies of complexes of colchicine with Zn(II).

  2. Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants?

    Science.gov (United States)

    Gunes, Muhammed; Cekic, Sukru; Kilic, Sara Sebnem

    2017-06-01

    Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most frequent repetitive fever syndrome in childhood. It is characterized by fever episodes lasting for approximately 3-6 days, once every 3-8 weeks. Clinical and laboratory data for PFAPA syndrome patients between January 2010 and December 2014 followed up at a tertiary pediatric care hospital were reviewed. Four hundred children (256 male, 144 female; mean age at diagnosis, 4.2 ± 2.2 years), were enrolled in the study. During the episodes, mean leukocyte number was high (12 725/mm 3 ) with predominant neutrophils. The mean number of monocytes was 1256/mm 3 , and 90.2% had monocytosis. Serum amyloid A and C-reactive protein were high in 84.6% and in 77.8% of the patients, respectively. Mediterranean fever (MEFV) gene heterozygous mutation was identified in 57 of the 231 patients (24.7%) in whom genetic analysis had been performed. The most frequent mutation was heterozygous M694V (10%, n = 23). Extension of between-episode interval following prophylaxis was noted in 85% of those on regular colchicine treatment (n = 303). In the colchicine group, between-episode interval was prolonged from 18.8 ± 7.9 days (before colchicine treatment) to 49.5 ± 17.6 days on prophylactic colchicine therapy; also, prophylactic treatment was more effective in reducing episode frequency in patients with MEFV gene variant (n = 54, 96%) than in those without (n = 122, 80%; P = 0.003). This study has involved the largest number of PFAPA syndrome patients in the literature. It is particularly important to assess and to demonstrate the high rate of response to colchicine prophylaxis in PFAPA syndrome patients, especially those with MEFV variant. On blood screening, neutrophilia associated with monocytosis and low procalcitonin could contribute to diagnosis. © 2017 Japan Pediatric Society.

  3. Colchicine application significantly affects plant performance in the second generation of synthetic polyploids and its effects vary between populations.

    Science.gov (United States)

    Münzbergová, Zuzana

    2017-08-01

    Understanding the direct consequences of polyploidization is necessary for assessing the evolutionary significance of this mode of speciation. Previous studies have not studied the degree of between-population variation that occurs due to these effects. Although it is assumed that the effects of the substances that create synthetic polyploids disappear in second-generation synthetic polyploids, this has not been tested. The direct consequences of polyploidization were assessed and separated from the effects of subsequent evolution in Vicia cracca , a naturally occurring species with diploid and autotetraploid cytotypes. Synthetic tetraploids were created from diploids of four mixed-ploidy populations. Performance of natural diploids and tetraploids was compared with that of synthetic tetraploids. Diploid offspring of the synthetic tetraploid mothers were also included in the comparison. In this way, the effects of colchicine application in the maternal generation on offspring performance could be compared independently of the effects of polyploidization. The sizes of seeds and stomata were primarily affected by cytotype, while plant performance differed between natural and synthetic polyploids. Most performance traits were also determined by colchicine application to the mothers, and most of these results were largely population specific. Because the consequences of colchicine application are still apparent in the second generation of the plants, at least the third-generation polyploids should be considered in future comparisons. The specificities of the colchicine-treated plants may also be caused by strong selection pressures during the creation of synthetic polyploids. This could be tested by comparing the initial sizes of plants that survived the colchicine treatments with those of plants that did not. High variation between populations also suggests that different polyploids follow different evolutionary trajectories, and this should be considered when

  4. Real Closed Rings and Real Closed * Rings

    OpenAIRE

    Capco, Jose

    2007-01-01

    Here we try to distinguish and compare different notions of real closedness mainly one developed by N. Schwartz in his Habilitationschrift and the other developed by A. Sankaranand K. Varadarajan which we shall call real closed *. We stick to the definition of real closed rings as defined and characterized N. Schwartz and we try to determine and characterize real closed rings that are real closed *. The main result is that real closed rings have unique real closure * and that real closure of ...

  5. A calorimetric study on interactions of colchicine with human serum albumin

    Science.gov (United States)

    Zhao, Qiang; Xu, Xiang-Yu; Sun, Xiang-Jun; Liu, Min; Sun, De-Zhi; Li, Lin-Wei

    2009-08-01

    Interaction of colchicine (COL) with human serum albumin (HSA) in buffer solutions (pH 7.2) has been investigated by isothermal titration calorimetry (ITC) combined with circular dichroism (CD) and UV-vis spectra. Heats of the interactions have been determined at 298.15 K. Based on the calorimetric data and reasonable suppositions for the bio-macromolecule - ligand binding process, the equilibrium constants, standard changes of enthalpy, entropy and Gibbs free energy of the processes are obtained. The results show that there are two classes of ligand binding sites. The first-class binding is mainly driven by entropy, while the second-class binding is synergistically driven by entropy and enthalpy. Circular dichroism (CD) and UV-vis spectra show that COL can change the secondary structure of HSA molecule.

  6. Inhibitory effect of pironetin analogue/colchicine hybrids on the expression of the VEGF, hTERT and c-Myc genes.

    Science.gov (United States)

    Vilanova, Concepción; Díaz-Oltra, Santiago; Murga, Juan; Falomir, Eva; Carda, Miguel; Marco, J Alberto

    2015-08-15

    A small group of hybrid molecules composed of a colchicine moiety and a pironetin analogue fragment have been investigated for their ability to inhibit the expression of the VEGF, hTERT and c-Myc genes. The VEGF gene is involved in the generation of the vascular endothelial growth factor (VEGF) and thus in the angiogenic process whereas the two latter ones are related to the activation of telomerase. All three genes therefore may be of paramount importance in the cancer generation process. It has been found that colchicine and some of its derivatives display a measurable ability to inhibit the expression of the VEGF and the two other telomerase-related genes. In the case of some of the hybrids, the available data point to the colchicine fragment being responsible for the observed biological activities. It is the first time that the last biological feature has been reported for colchicine or derivatives thereof. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The first F-ring modified ciguatoxin analogue showing significant toxicity.

    Science.gov (United States)

    Ishihara, Yuuki; Lee, Nayoung; Oshiro, Naomasa; Matsuoka, Shigeru; Yamashita, Shuji; Inoue, Masayuki; Hirama, Masahiro

    2010-05-07

    Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are potent neurotoxic polycyclic ethers. We report herein the total synthesis of a 10-membered F-ring analogue of 51-hydroxyCTX3C, which constitutes the first example of an F-ring modified ciguatoxin that exhibits potent cytotoxicity as well as mouse acute toxicity.

  8. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  9. Genetic changes in oral premalignant lesion, condition, and oral squamous cell carcinoma - A study based on inhibition of G2M phase by colchicines

    Directory of Open Access Journals (Sweden)

    Santosh Kanwar

    2017-01-01

    Full Text Available Aims: To assess the percentage of cell arrested in G2M phase by colchicine in the early detection and prognosis of oral cancer, by comparison of oral squamous cell with leukoplakia and oral submucous fibrosis (OSMF using flow cytometry analysis. Materials and Methods: Biopsy samples 5 each of clinically diagnosed and histopathologically confirmed case of leukoplakia, OSMF, and squamous cell carcinoma (SCC are included in the study. Results: Colchicines significantly inhibited the growth of oral SCC-9 cell line by arresting G2M phase of the cell cycle (94.90%. This cell cycle result indicated that doubling of DNA is a characteristic feature of cancer. Colchicines significantly inhibited the G2M phase of the cell cycle in leukoplakia (33.51% as compared to control (23.60%. Colchicines marginally inhibited the G2M phase of the cell cycle in OSMF (31.83% as compared to control (28.36%. Colchicines significantly inhibited the G2M phase of the cell cycle in SCC (63.05% as compared to control (26.40%. Conclusion: DNA analysis by inhibition of G2M phase of cell cycle using colchicine facilitates early detection and also helps determine the prognosis of leukoplakia, OSMF, and oral cancer.

  10. Birth Control Ring

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Birth Control Ring KidsHealth / For Teens / Birth Control Ring What's in this article? What Is ... español Anillo vaginal anticonceptivo What Is It? The birth control ring is a soft, flexible, doughnut-shaped ...

  11. Physics of quantum rings

    CERN Document Server

    Fomin, Vladimir M

    2013-01-01

    This book deals with a new class of materials, quantum rings. Innovative recent advances in experimental and theoretical physics of quantum rings are based on the most advanced state-of-the-art fabrication and characterization techniques as well as theoretical methods. The experimental efforts allow to obtain a new class of semiconductor quantum rings formed by capping self-organized quantum dots grown by molecular beam epitaxy. Novel optical and magnetic properties of quantum rings are associated with non-trivial topologies at the nanoscale. An adequate characterization of quantum rings is po

  12. Synthesis, antimicrobial and cytotoxic activities of sulfonamidomethane linked heterocycles.

    Science.gov (United States)

    Swapna, Mukkara; Premakumari, Chokkappagari; Reddy, Sanapalli Nagi; Padmaja, Adivireddy; Padmavathi, Venkatapuram; Kondaiah, Paturu; Krishna, Narra Siva

    2013-01-01

    A new class of sulfonamidomethane pyrrolyl-oxadiazoles/thiadiazoles and pyrazolyl-oxadiazoles/thiadiazoles was prepared from arylsulfonylaminoacetic acid hydrazides and E-cinnamic acid. The lead compounds were tested for antimicrobial and cytotoxic activities. The thiadiazole compounds having chloro substituent on the aromatic ring 4c, 8c and 10c exhibited comparable antibacterial activity against Pseudomonas aeruginosa and also antifungal activity against Penicillium chrysogenum. The styryl oxadiazole compound 3c showed appreciable cytotoxic activity on A549 lung carcinoma cells which can be used as a lead compound in the future studies.

  13. Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery.

    Science.gov (United States)

    Wang, Yuxi; Zhang, Hang; Gigant, Benoît; Yu, Yamei; Wu, Yangping; Chen, Xiangzheng; Lai, Qinhuai; Yang, Zhaoya; Chen, Qiang; Yang, Jinliang

    2016-01-01

    Microtubules are dynamic assemblies of αβ-tubulin heterodimers and have been recognized as highly attractive targets for cancer chemotherapy. A broad range of agents bind to tubulin and interfere with microtubule assembly. Despite having a long history of characterization, colchicine binding site inhibitors (CBSIs) have not yet reached the commercial phase as anti-cancer drugs to date. We determined the structures of tubulin complexed with a set of structurally diverse CBSIs (lexibulin, nocodazole, plinabulin and tivantinib), among which nocodazole and tivantinib are both binary-function inhibitors targeting cancer-related kinases and microtubules simultaneously. High resolution structures revealed the detailed interactions between these ligands and tubulin. Our results showed that the binding modes of the CBSIs were different from previous docking models, highlighting the importance of crystal structure information in structure-based drug design. A real structure-based pharmacophore was proposed to rationalize key common interactions of the CBSIs at the colchicine domain. Our studies provide a solid structural basis for developing new anti-cancer agents for the colchicine binding site. The atomic coordinates and structure factors for tubulin complexed with lexibulin, nocodazole, plinabulin and tivantinib have been deposited in the Protein Data Bank under accession codes 5CA0, 5CA1, 5C8Y and 5CB4, respectively. © 2015 FEBS.

  14. Proteomic analysis of the low mutation rate of diploid male gametes induced by colchicine in Ginkgo biloba L.

    Directory of Open Access Journals (Sweden)

    Nina Yang

    Full Text Available Colchicine treatment of G. biloba microsporocytes results in a low mutation rate in the diploid (2n male gamete. The mutation rate is significantly lower as compared to other tree species and impedes the breeding of new economic varieties. Proteomic analysis was done to identify the proteins that influence the process of 2n gamete formation in G. biloba. The microsporangia of G. biloba were treated with colchicine solution for 48 h and the proteins were analyzed using 2-D gel electrophoresis and compared to protein profiles of untreated microsporangia. A total of 66 proteins showed difference in expression levels. Twenty-seven of these proteins were identified by mass spectrometry. Among the 27 proteins, 14 were found to be up-regulated and the rest 13 were down-regulated. The identified proteins belonged to five different functional classes: ATP generation, transport and carbohydrate metabolism; protein metabolism; ROS scavenging and detoxifying enzymes; cell wall remodeling and metabolism; transcription, cell cycle and signal transduction. The identification of these differentially expressed proteins and their function could help in analysing the mechanism of lower mutation rate of diploid male gamete when the microsporangium of G. biloba was induced by colchicine.

  15. Influence of dose-death interval on colchicine and metabolite distribution in decomposed skeletal tissues.

    Science.gov (United States)

    Imfeld, Anic B; Watterson, James H

    2016-03-01

    The semi-quantitative analysis of decomposed bone of rats exposed to colchicine and euthanized following different time intervals postexposure (i.e., dose-death interval, DDI) is described. Rats received colchicine (50 mg/kg, i.p.) and were euthanized 30 min (DDI1; n = 4), 60 min (DDI2; n = 4), or 180 min (DDI3; n = 4) postdose. Drug-free animals (n = 3) served as negative controls. Perimortem heart plasma was collected. Remains were decomposed to skeleton outdoors and then collected and sorted (skull, vertebrae, rib, pelvis, femur, tibia). Bones were dried, pulverized, and prepared by microwave-assisted extraction and microplate solid-phase extraction (MAE-MPSPE), followed by analysis for colchicine, 3-demethylcolchicine (3DMC), and 2-demethylcolchicine (2DMC) by ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA) at 350 nm. Bone type was a main effect (Kruskall-Wallis, p < 0.05) with respect to drug level (expressed as mass-normalized response ratio, RR/m) for each analyte, at each DDI. For all samples, DDI was a main effect (Kruskall-Wallis, p < 0.05) with respect to analyte level, and the ratio of analyte levels (RR3DMC/RRCOLCH, RR2DMC/RRCOLCH, and RR2DMC/RR3DMC). Bone COLCH levels varied by 19-fold, 12-fold, and 60-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 3DMC levels varied by 12-fold, 11-fold and 17-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 2DMC levels varied by 20-fold, 14-fold, and 14-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR3DMC/RRCOLCH varied by 16-fold, 5-fold, and 5-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR2DMC/RRCOLCH varied by 10-fold, 6-fold, and 12-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR2DMC/RR3DMC varied by 3-fold, 5-fold, and 2-fold across all bone types in the DDI1, DDI2, and DDI3 groups

  16. The Effects of Colchicine on Risk of Cardiovascular Events and Mortality Among Patients with Gout: A Cohort Study Using Electronic Medical Records Linked with Medicare Claims

    Science.gov (United States)

    Solomon, Daniel H.; Liu, Chih-Chin; Kuo, I-Hsin; Zak, Agnes; Kim, Seoyoung C.

    2016-01-01

    Background Colchicine may have beneficial effects on cardiovascular (CV) disease, but there are sparse data on its CV effect among patients with gout. We examined the potential association between colchicine and CV risk and all-cause mortality in gout. Methods The analyses used data from an electronic medical record (EMR) database linked with Medicare claims (2006–2011). To be eligible for the study cohort, subjects must have had a diagnosis of gout in the EMR and Medicare claims. New users of colchicine were identified and followed-up from the first colchicine dispensing date. Non-users had no evidence of colchicine prescriptions during the study period and were matched to users on the start of follow-up, age, and gender. Both groups were followed for the primary outcome, a composite of myocardial infarction (MI), stroke or transient ischemic attack (TIA). We calculated hazard ratios (HRs) in Cox regression, adjusting for potential confounders. Results We matched 501 users with an equal number of non-users with a median follow-up of 16.5 months. During follow-up, 28 primary CV events were observed among users and 82 among non-users. Incidence rates per 1,000 person-years were 35.6 for users and 81.8 for non-users. After full adjustment, colchicine use was associated with a 49% lower risk (HR 0.51, 95% CI 0.30 – 0.88) in the primary CV outcome as well as a 73% reduction in all-cause mortality (HR 0.27, 95% CI 017 – 0.43). Conclusion Colchicine use was associated with a reduced risk of a CV event among patients with gout. PMID:26582823

  17. Improved production of doubled haploids of winter and spring triticale hybrids via combination of colchicine treatments on anthers and regenerated plants.

    Science.gov (United States)

    Ślusarkiewicz-Jarzina, Aurelia; Pudelska, Hanna; Woźna, Jolanta; Pniewski, Tomasz

    2017-08-01

    Double haploids (DH), obtained during androgenesis in vitro or by genome diploidisation in regenerated haploids, are one type of basic materials used in triticale breeding programmes. The aim of this study was to improve DH production by a combination of colchicine treatment methods on a sample of five winter and five spring triticale hybrids. Colchicine was applied in vitro either in the C17 medium to induce embryo-like structures (ELS) or in the 190-2 medium for green plant (GP) development. Regenerants which remained haploid were immersed in a colchicine solution either when placed on the medium prior to transferring to soil or when growing in pots, followed by the application or absence of cooling. Colchicine treatment during anther culture affected neither ELS nor GP development, but significantly increased the number of DH plants in comparison to spontaneous chromosome doubling. The highest efficiency was recorded when colchicine was applied in the induction medium (55%) versus the regeneration medium (44.5%) or no colchicine treatment (30%). The effectiveness of chromosome duplication in haploid plants ranged from 32 to 64.5% and it was the highest for the treatment on the medium followed by cooling. Individual hybrids differed regarding their capability of regeneration and chromosome doubling, which were consistent only to a low or moderate extent. However, taken together, winter and spring hybrids did not differ significantly. Combined colchicine application resulted in a high yield of DH production, 82.6% for all triticale hybrids, and can provide a considerable number of fertile DH lines for triticale breeding programmes.

  18. Cytotoxicity of fluorographene

    Czech Academy of Sciences Publication Activity Database

    Teo, W. Z.; Sofer, Z.; Šembera, Filip; Janoušek, Zbyněk; Pumera, M.

    2015-01-01

    Roč. 5, č. 129 (2015), s. 107158-107165 ISSN 2046-2069 R&D Projects: GA ČR(CZ) GA15-09001S Institutional support: RVO:61388963 Keywords : fluorinated graphene * viability assays * cytotoxicity Subject RIV: CC - Organic Chemistry Impact factor: 3.289, year: 2015

  19. Brane world black rings

    International Nuclear Information System (INIS)

    Sahay, Anurag; Sengupta, Gautam

    2007-01-01

    Five dimensional neutral rotating black rings are described from a Randall-Sundrum brane world perspective in the bulk black string framework. To this end we consider a rotating black string extension of a five dimensional black ring into the bulk of a six dimensional Randall-Sundrum brane world with a single four brane. The bulk solution intercepts the four brane in a five dimensional black ring with the usual curvature singularity on the brane. The bulk geodesics restricted to the plane of rotation of the black ring are constructed and their projections on the four brane match with the usual black ring geodesics restricted to the same plane. The asymptotic nature of the bulk geodesics are elucidated with reference to a bulk singularity at the AdS horizon. We further discuss the description of a brane world black ring as a limit of a boosted bulk black 2 brane with periodic identification

  20. Token Ring Project

    Directory of Open Access Journals (Sweden)

    Adela Ionescu

    2007-01-01

    Full Text Available Ring topology is a simple configuration used to connect processes that communicate among themselves. A number of network standards such as token ring, token bus, and FDDI are based on the ring connectivity. This article will develop an implementation of a ring of processes that communicate among themselves via pipe links. The processes are nodes in the ring. Each process reads from its standard input and writes in its standard output. N-1 process redirects the its standard output to a standard input of the process through a pipe. When the ring-structure is designed, the project can be extended to simulate networks or to implement algorithms for mutual exclusion

  1. Token ring technology report

    CERN Document Server

    2013-01-01

    Please note this is a Short Discount publication. This report provides an overview of the IBM Token-Ring technology and products built by IBM and compatible vendors. It consists of two sections: 1. A summary of the design trade-offs for the IBM Token-Ring. 2. A summary of the products of the major token-ring compatible vendors broken down by adapters and components, wiring systems, testing, and new chip technology.

  2. Spannungsgesteuerter Ring-Oszillator

    OpenAIRE

    Wang, Z.; Thiede, A.

    1999-01-01

    The oscillator (1) of integrated monolithic design has several analogue amplifier units (2) connected in a ring. The individual amplifiers are frequency selective in regard to a resonance frequency. The phase displacements of the amplifiers are chosen so that the total phase displacement over the ring at the resonance frequencies of the amplifiers amounts to 3600 or a whole number multiple of that. The number of amplifiers selected corresponds to the overall quality factor for the ring oscill...

  3. Radioactive gold ring dermatitis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, R.A.; Aldrich, J.E. (Dalhousie Univ., Halifax, Nova Scotia (Canada))

    1990-08-01

    A superficial squamous cell carcinoma developed in a woman who wore a radioactive gold ring for more than 30 years. Only part of the ring was radioactive. Radiation dose measurements indicated that the dose to basal skin layer was 2.4 Gy (240 rad) per week. If it is assumed that the woman continually wore her wedding ring for 37 years since purchase, she would have received a maximum dose of approximately 4600 Gy.

  4. Vortex and source rings

    DEFF Research Database (Denmark)

    Branlard, Emmanuel Simon Pierre

    2017-01-01

    The velocity field, vector potential and velocity gradient of a vortex ring is derived in this chapter. The Biot-Savart law for the vector potential and velocity is expressed in a first section. Then, the flow is derived at specific locations: on the axis, near the axis and in the far field where...... is dedicated to vortex rings. Source rings are only briefly mentioned....

  5. Radioactive gold ring dermatitis

    International Nuclear Information System (INIS)

    Miller, R.A.; Aldrich, J.E.

    1990-01-01

    A superficial squamous cell carcinoma developed in a woman who wore a radioactive gold ring for more than 30 years. Only part of the ring was radioactive. Radiation dose measurements indicated that the dose to basal skin layer was 2.4 Gy (240 rad) per week. If it is assumed that the woman continually wore her wedding ring for 37 years since purchase, she would have received a maximum dose of approximately 4600 Gy

  6. The ring laser gyro

    Science.gov (United States)

    Chow, W. W.; Gea-Banacloche, J.; Pedrotti, L. M.; Sanders, V. E.; Schleich, W.; Scully, M. O.

    1985-01-01

    This paper presents a review of both active and passive ring laser devices. The operating principles of the ring laser are developed and discussed, with special emphasis given to the problems associated with the achievement of greater sensitivity and stability. First-principle treatments of the nature of quantum noise in the ring laser gyro and various methods designed to avoid low-rotation-rate lock-in are presented. Descriptions of state-of-the-art devices and current and proposed applications (including a proposed test of metric theories of gravity using a passive cavity ring laser) are given.

  7. Cytotoxic Cardenolides from Calotropis Species: A Short Review

    Directory of Open Access Journals (Sweden)

    Eric Wei Chiang Chan

    2017-07-01

    Full Text Available From different plant parts of Calotropis species (C. gigantea and C. procera, various classes of compounds such as oxy pregnanes, terpenoids, sterols, cardenolides and flavonoids have been isolated. Of these compounds, the cardenolides stand out as many of them have anticancer properties. Cardenolides are C 23 steroids with a five-membered unsaturated butyrolactone ring consisting of a steroid nucleus, a lactone moiety at C-17 and a sugar moiety at C-3. The roles of cardenolides in the treatment of human cancer have been established as they can induce apoptosis and inhibit the growth of cancer cells. Structure‒activity relationship analyses have yielded some interesting findings on their cytotoxicity. Compounds with six-membered ring sugar groups generally have significantly stronger inhibitory activity than those with five-membered ring sugar groups. A formyl or methyl-hydroxyl group at C-10 enhances cytotoxicity while the presence of a 4´-OH or 16-OH group decreases cytotoxicity. Chemical modification of 2”-oxovoruscharin, a novel cardenolide extracted from the root bark of C. procera, has led to the synthesis of UNBS1450. The compound is characterized by more potent anti-proliferative activity, lower toxicity, and is a strong sodium pump inhibitor and inducer of non-apoptotic cell death. UNBS1450 is currently in Phase I clinical trials.

  8. Medication errors with the use of allopurinol and colchicine: a retrospective study of a national, anonymous Internet-accessible error reporting system.

    Science.gov (United States)

    Mikuls, Ted R; Curtis, Jeffrey R; Allison, Jeroan J; Hicks, Rodney W; Saag, Kenneth G

    2006-03-01

    To more closely assess medication errors in gout care, we examined data from a national, Internet-accessible error reporting program over a 5-year reporting period. We examined data from the MEDMARX database, covering the period from January 1, 1999 through December 31, 2003. For allopurinol and colchicine, we examined error severity, source, type, contributing factors, and healthcare personnel involved in errors, and we detailed errors resulting in patient harm. Causes of error and the frequency of other error characteristics were compared for gout medications versus other musculoskeletal treatments using the chi-square statistic. Gout medication errors occurred in 39% (n = 273) of facilities participating in the MEDMARX program. Reported errors were predominantly from the inpatient hospital setting and related to the use of allopurinol (n = 524), followed by colchicine (n = 315), probenecid (n = 50), and sulfinpyrazone (n = 2). Compared to errors involving other musculoskeletal treatments, allopurinol and colchicine errors were more often ascribed to problems with physician prescribing (7% for other therapies versus 23-39% for allopurinol and colchicine, p < 0.0001) and less often due to problems with drug administration or nursing error (50% vs 23-27%, p < 0.0001). Our results suggest that inappropriate prescribing practices are characteristic of errors occurring with the use of allopurinol and colchicine. Physician prescribing practices are a potential target for quality improvement interventions in gout care.

  9. EBT ring physics

    International Nuclear Information System (INIS)

    Uckan, N.A.

    1980-04-01

    This workshop attempted to evaluate the status of the current experimental and theoretical understanding of hot electron ring properties. The dominant physical processes that influence ring formation, scaling, and their optimal behavior are also studied. Separate abstracts were prepared for each of the 27 included papers

  10. Children of Sex Rings.

    Science.gov (United States)

    Hunt, Patricia; Baird, Margaret

    1990-01-01

    Outlines three major differentiating categories of children who were sexually abused by sex rings: level of fear, ability to trust, and disclosure confusion. Addresses denial and resistance regarding child sexual exploitation by a ring among practitioners in the child welfare system. (Author/BB)

  11. Illustration of Saturn's Rings

    Science.gov (United States)

    2001-01-01

    This illustration shows a close-up of Saturn's rings. These rings are thought to have formed from material that was unable to form into a Moon because of tidal forces from Saturn, or from a Moon that was broken up by Saturn's tidal forces.

  12. Relativistic ring models

    Energy Technology Data Exchange (ETDEWEB)

    Ujevic, Maximiliano [Universidade Federal do ABC (UFABC), Santo Andre, SP (Brazil). Centro de Ciencias Naturais e Humanas; Letelier, Patricio S.; Vogt, Daniel [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Matematica, Estatistica e Computacao Cientifica. Dept. de Matematica Aplicada

    2011-07-01

    Full text: Relativistic thick ring models are constructed using previously found analytical Newtonian potential-density pairs for flat rings and toroidal structures obtained from Kuzmin-Toomre family of discs. This was achieved by inflating previously constructed Newtonian ring potentials using the transformation |z|{yields}{radical}z{sup 2} + b{sup 2}, and then finding their relativistic analog. The models presented have infinite extension but the physical quantities decays very fast with the distance, and in principle, one could make a cut-off radius to consider it finite. In particular, we present systems with one ring, two rings and a disc with a ring. Also, the circular velocity of a test particle and its stability when performing circular orbits are presented in all these models. Using the Rayleigh criterion of stability of a fluid at rest in a gravitational field, we find that the different systems studied present a region of non-stability that appears in the intersection of the disc and the ring, and between the rings when they become thinner. (author)

  13. Imaging rings in ring imaging Cherenkov counters

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliff, Blair N

    2002-11-25

    The general concepts used to form images in Ring Imaging Cherenkov (RICH) counters are described and their performance properties compared. Particular attention is paid to issues associated with imaging in the time dimension, especially in Detectors of Internally Reflected Cherenkov light (DIRCs).

  14. Flavonoids of Calligonum polygonoides and their cytotoxicity.

    Science.gov (United States)

    Ahmed, Hayam; Moawad, Abeer; Owis, Asmaa; AbouZid, Sameh; Ahmed, Osama

    2016-10-01

    Context Calligonum polygonoides L. subsp. comosum L' Hér. (Polygonaceae), locally known as "arta", is a slow-growing small leafless desert shrub. Objective Isolation, structure elucidation and evaluation of cytotoxic activity of flavonoids from C. polygonoides aerial parts. Materials and methods Flavonoids in the hydroalcoholic extract of the of C. polygonoides were isolated and purified using column chromatography and preparative HPLC. The structures of the isolated flavonoids were elucidated on the basis of spectroscopic data including 2D NMR techniques. The cytotoxic activity of the isolated flavonoids (6.25, 25, 50 and 100 μg/mL) was evaluated against liver HepG2 and breast MCF-7 cancer cell lines using sulphorhodamine-B assay. Results A new flavonoid, kaempferol-3-O-β-D-(6″-n-butyl glucuronide) (1), and 13 known flavonoids, quercetin 3-O-β-D-(6″-n-butyl glucuronide) (2), kaempferol-3-O-β-D-(6″-methyl glucuronide) (3), quercetin-3-O-β-D-(6″-methyl glucuronide) (4), quercetin-3-O-glucuronide (5), kaempferol-3-O-glucuronide (6), quercetin-3-O-α-rhamnopyranoside (7), astragalin (8), quercetin-3-O-glucopyranoside (9), taxifolin (10), (+)-catechin (11), dehydrodicatechin A (12), quercetin (13), and kaempferol (14), were isolated from the aerial parts of C. polygonoides. Quercetin showed significant cytotoxic activity against HepG2 and MCF-7 cell lines with IC50 values of 4.88 and 0.87 μg/mL, respectively. Structure-activity relationships were analyzed by comparing IC50 values of several pairs of flavonoids differing in one structural element. Discussion and conclusion The activity against breast cancer cell lines decreased by glycosylation at C-3. The presence of 2,3-double bond in ring C, carbonyl group at C-4 and 3',4'-dihydroxy substituents in ring B are essential structural requirements for the cytotoxic activity against breast cancer cells.

  15. Cytotoxicity assay automation

    Science.gov (United States)

    Levinthal, E. C.; Payne, R. O.

    1971-01-01

    The design and construction of a system to automatically test HLP antigens are described. Major efforts were made to test and evaluate the performance of such a system, and compare its performance with nonautomatic tissue typing techniques. The system is based on the fluorochromatic cytotoxicity assay. Results show the system will work but is subject to malfunctions after a few samplings, and poses problems in showing correctly the necessary readings.

  16. Rings and their modules

    CERN Document Server

    Bland, Paul E

    2011-01-01

    This book is an introduction to the theory of rings and modules that goes beyond what one normally obtains in a graduate course in abstract algebra. In addition to the presentation of standard topics in ring and module theory, it also covers category theory, homological algebra and even more specialized topics like injective envelopes and projective covers, reflexive modules and quasi-Frobenius rings, and graded rings and modules. The book is a self-contained volume written in a very systematic style: allproofs are clear and easy for the reader to understand and allarguments are based onmaterials contained in the book. A problem sets follow each section. It is suitable for graduate and PhD students who have chosen ring theory for their research subject.

  17. Biochemical studies of mouse brain tubulin: colchicine binding (DEAE-cellulose filter) assay and subunits (α and β) biosynthesis and degradation (in newborn brain)

    International Nuclear Information System (INIS)

    Tse, C.F.

    1978-01-01

    A DEAE-cellulose filter assay, measuring [ 3 H]colchicine bound to colchicine binding protein (CBP) absorbed on filter discs, has been modified to include lM sucrose in the incubation medium for complexing colchicine to CBP in samples before applying the samples to filter discs (single point assay). Due to the much greater stability of colchicine binding capacity in the presence of lM sucrose, multiple time-point assays and least squares linear regression analysis were not necessary for accurate determination of CBP in hybrid mouse brain at different stages of development. The highest concentrations of CBP were observed in the 160,000g supernatant and pellet of newborn brain homogenate. Further studies of the modified filter assay documented that the assay has an overall counting efficiency of 27.3%, that DEAE-cellulose filters bind and retain all tubulin in the assay samples, and that one molecule of colchicine binds approximately one molecule of tubulin dimer. Therefore, millimoles of colchicine bound per milligram total protein can be used to calculate tubulin content. With this technique tubulin content of brain supernatant was found to be 11.9% for newborn, and 7.15% for 11 month old mice. Quantitative densitometry was also used to measure mouse brain supernatant actin content for these two stages. In vivo synthesis and degradation rates of tubulin α and β subunits of two day mouse brain 100,000g supernatant were studied after intracerebral injection of [ 3 H]leucine. Quantitative changes of the ratio of tritium specific activities of tubulin α and β subunits with time were determined. The pattern of change was biphasic. During the first phase the ratio decreased; during the second phase the ratio increased continuously. An interpretation consistent with all the data in this study is that the α subunit is synthesized at a more rapid rate than the β subunit

  18. Biochemical studies of mouse brain tubulin: colchicine binding (DEAE-cellulose filter) assay and subunits ( α and β) biosynthesis and degradation (in newborn brain)

    Energy Technology Data Exchange (ETDEWEB)

    Tse, Cek-Fyne [Univ. of Rochester, NY (United States)

    1978-01-01

    A DEAE-cellulose filter assay, measuring (3H)colchicine bound to colchicine binding protein (CBP) absorbed on filter discs, has been modified to include lM sucrose in the incubation medium for complexing colchicine to CBP in samples before applying the samples to filter discs (single point assay). Due to the much greater stability of colchicine binding capacity in the presence of lM sucrose, multiple time-point assays and least squares linear regression analysis were not necessary for accurate determination of CBP in hybrid mouse brain at different stages of development. The highest concentrations of CBP were observed in the 160,000g supernatant and pellet of newborn brain homogenate. Further studies of the modified filter assay documented that the assay has an overall counting efficiency of 27.3%, that DEAE-cellulose filters bind and retain all tubulin in the assay samples, and that one molecule of colchicine binds approximately one molecule of tubulin dimer. Therefore, millimoles of colchicine bound per milligram total protein can be used to calculate tubulin content. With this technique tubulin content of brain supernatant was found to be 11.9% for newborn, and 7.15% for 11 month old mice. Quantitative densitometry was also used to measure mouse brain supernatant actin content for these two stages. In vivo synthesis and degradation rates of tubulin ..cap alpha.. and ..beta.. subunits of two day mouse brain 100,000g supernatant were studied after intracerebral injection of (3H)leucine. Quantitative changes of the ratio of tritium specific activities of tubulin ..cap alpha.. and ..beta.. subunits with time were determined. The pattern of change was biphasic. During the first phase the ratio decreased; during the second phase the ratio increased continuously. An interpretation consistent with all the data in this study is that the ..cap alpha.. subunit is synthesized at a more rapid rate than the ..beta.. subunit. (ERB)

  19. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...... with the probe L1.26 confirmed the derivation from chromosome 13 and DNA polymorphism analysis showed maternal origin of the ring chromosome. Our results, together with a review of previous reports of cases with ring chromosome 13 with identified breakpoints, could neither support the theory of distinct clinical...

  20. Faithfully quadratic rings

    CERN Document Server

    Dickmann, M

    2015-01-01

    In this monograph the authors extend the classical algebraic theory of quadratic forms over fields to diagonal quadratic forms with invertible entries over broad classes of commutative, unitary rings where -1 is not a sum of squares and 2 is invertible. They accomplish this by: (1) Extending the classical notion of matrix isometry of forms to a suitable notion of T-isometry, where T is a preorder of the given ring, A, or T = A^2. (2) Introducing in this context three axioms expressing simple properties of (value) representation of elements of the ring by quadratic forms, well-known to hold in

  1. Survival and differentiation of Oncidium flexuosum protocorm submitted to peracetic acid and colchicine treatment - DOI: 10.4025/actasciagron.v31i3.697

    OpenAIRE

    Unemoto, Lilian Keiko; UEL; Faria, Ricardo Tadeu de; UEL; Destro, Deonisio; UEL; Barbosa, Cristiane Muniz; UEL; Lone, Alessandro Borini; UEL

    2009-01-01

    The objective of this work was to evaluate the effect of colchicine, when applied at different times on O. flexuosum protocorm differentiation. Peracetic acid was previously tested at 0, 3, 6 and 9 mL L-1 concentrations for 10 days, in order to verify the efficacy on the culture medium sterilization and the possible phytotoxic effects on protocorms. After determining the concentration, 6 mL L-1 of peracetic acid were added in MS medium with 0.05% colchicine and DMSO 1%. The protocorms were ag...

  2. The g-2 ring

    CERN Multimedia

    1974-01-01

    The precise measurement of "g-2", the anomalous magnetic moment of the muon, required a special muon storage ring with electrostatic focussing and very accurate knowledge of the magnetic bending field. For more details see under photo 7405430.

  3. Saturn's dynamic D ring

    Science.gov (United States)

    Hedman, M.M.; Burns, J.A.; Showalter, M.R.; Porco, C.C.; Nicholson, P.D.; Bosh, A.S.; Tiscareno, M.S.; Brown, R.H.; Buratti, B.J.; Baines, K.H.; Clark, R.

    2007-01-01

    The Cassini spacecraft has provided the first clear images of the D ring since the Voyager missions. These observations show that the structure of the D ring has undergone significant changes over the last 25 years. The brightest of the three ringlets seen in the Voyager images (named D72), has transformed from a narrow, <40-km wide ringlet to a much broader and more diffuse 250-km wide feature. In addition, its center of light has shifted inwards by over 200 km relative to other features in the D ring. Cassini also finds that the locations of other narrow features in the D ring and the structure of the diffuse material in the D ring differ from those measured by Voyager. Furthermore, Cassini has detected additional ringlets and structures in the D ring that were not observed by Voyager. These include a sheet of material just interior to the inner edge of the C ring that is only observable at phase angles below about 60??. New photometric and spectroscopic data from the ISS (Imaging Science Subsystem) and VIMS (Visual and Infrared Mapping Spectrometer) instruments onboard Cassini show the D ring contains a variety of different particle populations with typical particle sizes ranging from 1 to 100 microns. High-resolution images reveal fine-scale structures in the D ring that appear to be variable in time and/or longitude. Particularly interesting is a remarkably regular, periodic structure with a wavelength of ??? 30 ?? km extending between orbital radii of 73,200 and 74,000 km. A similar structure was previously observed in 1995 during the occultation of the star GSC5249-01240, at which time it had a wavelength of ??? 60 ?? km. We interpret this structure as a periodic vertical corrugation in the D ring produced by differential nodal regression of an initially inclined ring. We speculate that this structure may have formed in response to an impact with a comet or meteoroid in early 1984. ?? 2006 Elsevier Inc. All rights reserved.

  4. Child sex rings.

    OpenAIRE

    Wild, N J; Wynne, J M

    1986-01-01

    Details of 11 child sex rings identified in one working class community were obtained by interviewing investigating police officers and examining health and social services records. The rings contained 14 adult male perpetrators and 175 children aged 6-15 years. Most perpetrators used child ringleaders to recruit victims; others became a "family friend" or obtained a position of authority over children. Secrecy was encouraged and bribery, threats, and peer pressure used to induce participatio...

  5. Storage ring group summary

    International Nuclear Information System (INIS)

    King, N.M.

    1980-01-01

    The Storage Ring Group set out to identify and pursue salient problems in accelerator physics for heavy ion fusion, divorced from any particular reference design concept. However, it became apparent that some basic parameter framework was required to correlate the different study topics. As the Workshop progressed, ring parameters were modified and updated. Consequently, the accompanying papers on individual topics will be found to refer to slightly varied parameters, according to the stage at which the different problems were tackled

  6. Matrimonial ring structures

    OpenAIRE

    Hamberger, Klaus; Houseman, Michael; Daillant, Isabelle; White, Douglas R.; Barry, Laurent

    2006-01-01

    The paper deals with matrimonial rings, a particular kind of cycles in kinship networks which result when spouses are linked to each other by ties of consanguinity or affinity. By taking a network-analytic perspective, the paper endeavours to put this classical issue of structural kinship theory on a general basis, such as to allow conclusions which go beyond isolated discussions of particular ring types (like "cross-cousin marriage", "sister exchange", and so forth). The paper provides a def...

  7. Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.

    Science.gov (United States)

    Shankaraiah, Nagula; Nekkanti, Shalini; Brahma, Uma Rani; Praveen Kumar, Niggula; Deshpande, Namrata; Prasanna, Daasi; Senwar, Kishna Ram; Jaya Lakshmi, Uppu

    2017-09-01

    A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely, lung (A549 and NCI-H460), prostate (DU-145 and PC-3), colon (HCT-15 and HCT-116), and brain (U-87 glioblastoma) by MTT assay. Notably, among all the tested compounds, 4a exhibited potent cytotoxicity on NCI-H460 (lung cancer) cells with IC 50 of 1.48±0.19µM. The compound 4a showed significant inhibition of tubulin polymerization and disruption of the formation of microtubules (IC 50 of 9.66±0.06μM). Moreover, phase contrast microscopy and DAPI staining studies indicated that compound 4a can induce apoptosis in NCI-H460 cells. Further, the flow-cytometry analysis revealed that compound 4a arrests NCI-H460 cells in the G2/M phase of the cell cycle. In addition, molecular docking studies of the most active compounds 4a and 4b into the colchicine site of the tubulin, revealed the possible mode of interaction by these new conjugates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

    Science.gov (United States)

    Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

    2014-05-22

    Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

  9. Interaction of phenylbutazone and colchicine in binding to serum albumin in rheumatoid therapy: 1H NMR study

    Science.gov (United States)

    Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Sułkowski, W. W.

    2009-09-01

    The monitoring of drug concentration in blood serum is necessary in multi-drug therapy. Mechanism of drug binding with serum albumin (SA) is one of the most important factors which determine drug concentration and its transport to the destination tissues. In rheumatoid diseases drugs which can induce various adverse effects are commonly used in combination therapy. Such proceeding may result in the enhancement of those side effects due to drug interaction. Interaction of phenylbutazone and colchicine in binding to serum albumin and competition between them in gout has been studied by proton nuclear magnetic resonance ( 1H NMR) technique. The aim of the study was to determine the low affinity binding sites, the strength and kind of interaction between serum albumin and drugs used in combination therapy. The study of competition between phenylbutazone and colchicine in binding to serum albumin points to the change of their affinity to serum albumin in the ternary systems. This should be taken into account in multi-drug therapy. This work is a subsequent part of the spectroscopic study on Phe-COL-SA interactions [A. Sułkowska, et al., J. Mol. Struct. 881 (2008) 97-106].

  10. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation.

    Science.gov (United States)

    Robertson, Stacy; Martínez, Gonzalo J; Payet, Cloe A; Barraclough, Jennifer Y; Celermajer, David S; Bursill, Christina; Patel, Sanjay

    2016-07-01

    Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (PColchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (Pcolchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  11. Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells

    International Nuclear Information System (INIS)

    Muller, D.; Houpert, P.; Cambar, J.; Henge-Napoli, M-H.

    2006-01-01

    Although uranium is a well-characterized nephrotoxic agent, very little is known at the cellular and molecular level about the mechanisms underlying the uptake and toxicity of this element in proximal tubule cells. The aim of this study was thus to characterize the species of uranium that are responsible for its cytotoxicity and define the mechanism which is involved in the uptake of the cytotoxic fraction of uranium using two cell lines derived from kidney proximal (LLC-PK 1 ) and distal (MDCK) tubule as in vitro models. Treatment of LLC-PK 1 cells with colchicine, cytochalasin D, concanavalin A and PMA increased the sodium-dependent phosphate co-transport and the cytotoxicity of uranium. On the contrary, replacement of the extra-cellular sodium with N-methyl-D-glucamine highly reduced the transport of phosphate and the cytotoxic effect of uranium. Uranium cytotoxicity was also dependent upon the extra-cellular concentration of phosphate and decreased in a concentration-dependent manner by 0.1-10 mM phosphonoformic acid, a competitive inhibitor of phosphate uptake. Consistent with these observations, over-expression of the rat proximal tubule sodium-dependent phosphate co-transporter NaPi-IIa in stably transfected MDCK cells significantly increased the cytotoxicity of uranium, and computer modeling of uranium speciation showed that uranium cytotoxicity was directly dependent on the presence of the phosphate complexes of uranyl UO 2 (PO 4 ) - and UO 2 (HPO 4 ) aq . Taken together, these data suggest that the cytotoxic fraction of uranium is a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate co-transporter system

  12. Gold Nanoparticles Cytotoxicity

    Science.gov (United States)

    Mironava, Tatsiana

    Over the last two decades gold nanoparticles (AuNPs) have been used for many scientific applications and have attracted attention due to the specific chemical, electronic and optical size dependent properties that make them very promising agents in many fields such as medicine, imagine techniques and electronics. More specifically, biocompatible gold nanoparticles have a huge potential for use as the contrast augmentation agent in X-ray Computed Tomography and Photo Acoustic Tomography for early tumor diagnostic as well these nanoparticles are extensively researched for enhancing the targeted cancer treatment effectiveness such as photo-thermal and radiotherapy. In most biomedical applications biocompatible gold nanoparticles are labeled with specific tumor or other pathology targeting antibodies and used for site specific drug delivery. However, even though gold nanoparticles poses very high level of anti cancer properties, the question of their cytotoxicity ones they are released in normal tissue has to be researched. Moreover, the huge amount of industrially produced gold nanoparticles raises the question of these particles being a health hazard, since the penetration is fairly easy for the "nano" size substances. This study focuses on the effect of AuNPs on a human skin tissue, since it is fall in both categories -- the side effects for biomedical applications and industrial workers and users' exposure during production and handling. Therefore, in the present project, gold nanoparticles stabilized with the biocompatible agent citric acid were generated and characterized by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The cytotoxic effect of AuNPs release to healthy skin tissue was modeled on 3 different cell types: human keratinocytes, human dermal fibroblasts, and human adipose derived stromal (ADS) cells. The AuNPs localization inside the cell was found to be cell type dependent. Overall cytotoxicity was found to be dependent

  13. Cytotoxic constituents of Bursera permollis.

    Science.gov (United States)

    Wickramaratne, D B; Mar, W; Chai, H; Castillo, J J; Farnsworth, N R; Soejarto, D D; Cordell, G A; Pezzuto, J M; Kinghorn, A D

    1995-02-01

    Four cytotoxic lignans were isolated from the stem bark of Bursera permollis (Burseraceae), namely, deoxypodophyllotoxin (1), beta-peltatin methyl ether (2), picro-beta-peltatin methyl ether (3), and dehydro-beta-peltatin methyl ether (4). Also isolated was the inactive lignan, nemerosin (5). Compounds 1 and 2 were potently cytotoxic when evaluated against a panel of human cancer cell lines.

  14. BERKELEY: ALS ring

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Everybody at Lawrence Berkeley Laboratory's Center for Beam Physics is pleased with the rapid progress in commissioning LBL's Advanced Light Source (ALS) electron storage ring, the foundation for this third-generation synchrotron radiation facility. Designed for a maximum current of 400 mA, the ALS storage ring reached 407 mA just 24 days after storing the first beam on 16 March. ALS construction as a US Department of Energy (DOE) national user facility to provide high-brightness vacuum ultra-violet and soft x-ray radiation began in October 1987. One technical requirement marking project completion was to accumulate a 50-mA current in the storage ring. The ALS passed this milestone on 24 March, a week ahead of the official deadline. Once injected, the electron beam decays quasi-exponentially primarily because of interactions with residual gas molecules in the storage-ring vacuum chamber. Eventually, when the pressure in the vacuum chamber with beam decreases toward the expected operating level of 1 nano Torr, it will only be necessary to refill the storage ring at intervals of four to eight hours. At present the vacuum is improving rapidly as surfaces are irradiated (scrubbed) by the synchrotron radiation itself. At 100 mA, beam lifetime was about one hour (9 April)

  15. Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action

    Science.gov (United States)

    Marques-da-Silva, C; Chaves, MM; Castro, NG; Coutinho-Silva, R; Guimaraes, MZP

    2011-01-01

    BACKGROUND AND PURPOSE The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton might affect the functions of these receptors. EXPERIMENTAL APPROACH Functions of heterologously expressed P2X2 and P2X7 receptors were evaluated with electrophysiology and dye uptake following ATP application. Permeabilization and secretion of pro-inflammatory agents were quantified from fresh or cultured peritoneal mouse macrophages, treated in vitro or in vivo with colchicine. KEY RESULTS Disrupting the microtubule network with colchicine did not affect currents generated by ATP in P2X2 and P2X7 receptor-expressing cells but inhibited uptake of the dye Yo-Pro-1 in Xenopus oocytes and HEK293 cells expressing these channels. Peritoneal mouse macrophages showed less ATP-induced permeabilization to ethidium bromide in the presence of colchicine, and less reactive oxygen species (ROS) formation, nitric oxide (NO) and interleukin (IL)-1β release. Colchicine treatment did not affect ATP-evoked currents in macrophages. Finally, in vivo assays with mice inoculated with lipopolysaccharide and ATP showed diminished ROS, IL-1β, interferon-γ and NO production after colchicine treatment. CONCLUSIONS AND IMPLICATIONS Colchicine has known anti-inflammatory actions and is used to treat several conditions involving innate immunity, including gout and familial Mediterranean fever. Here we propose a new mechanism of action – inhibition of pore formation induced by activation of P2X receptors – which could explain some of the anti-inflammatory effects of colchicine. LINKED ARTICLE This article is commented on by Pelegrín, pp. 908–911 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01325.x PMID:21306580

  16. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial.

    Science.gov (United States)

    Imazio, Massimo; Belli, Riccardo; Brucato, Antonio; Cemin, Roberto; Ferrua, Stefania; Beqaraj, Federico; Demarie, Daniela; Ferro, Silvia; Forno, Davide; Maestroni, Silvia; Cumetti, Davide; Varbella, Ferdinando; Trinchero, Rita; Spodick, David H; Adler, Yehuda

    2014-06-28

    Colchicine is effective for the treatment of acute pericarditis and first recurrences. However, conclusive data are lacking for the efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis. We did this multicentre, double-blind trial at four general hospitals in northern Italy. Adult patients with multiple recurrences of pericarditis (≥two) were randomly assigned (1:1) to placebo or colchicine (0·5 mg twice daily for 6 months for patients weighing more than 70 kg or 0·5 mg once daily for patients weighing 70 kg or less) in addition to conventional anti-inflammatory treatment with aspirin, ibuprofen, or indometacin. Permuted block randomisation (size four) was done with a central computer-based automated sequence. Patients and all investigators were masked to treatment allocation. The primary outcome was recurrent pericarditis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00235079. 240 patients were enrolled and 120 were assigned to each group. The proportion of patients who had recurrent pericarditis was 26 (21·6%) of 120 in the colchicine group and 51 (42·5%) of 120 in the placebo group (relative risk 0·49; 95% CI 0·24-0·65; p=0·0009; number needed to treat 5). Adverse effects and discontinuation of study drug occurred in much the same proportions in each group. The most common adverse events were gastrointestinal intolerance (nine patients in the colchicine group vs nine in the placebo group) and hepatotoxicity (three vs one). No serious adverse events were reported. Colchicine added to conventional anti-inflammatory treatment significantly reduced the rate of subsequent recurrences of pericarditis in patients with multiple recurrences. Taken together with results from other randomised controlled trials, these findings suggest that colchicine should be probably regarded as a first-line treatment for either acute or recurrent pericarditis in the absence of

  17. Almost ring theory

    CERN Document Server

    2003-01-01

    This book develops thorough and complete foundations for the method of almost etale extensions, which is at the basis of Faltings' approach to p-adic Hodge theory. The central notion is that of an "almost ring". Almost rings are the commutative unitary monoids in a tensor category obtained as a quotient V-Mod/S of the category V-Mod of modules over a fixed ring V; the subcategory S consists of all modules annihilated by a fixed ideal m of V, satisfying certain natural conditions. The reader is assumed to be familiar with general categorical notions, some basic commutative algebra and some advanced homological algebra (derived categories, simplicial methods). Apart from these general prerequisites, the text is as self-contained as possible. One novel feature of the book - compared with Faltings' earlier treatment - is the systematic exploitation of the cotangent complex, especially for the study of deformations of almost algebras.

  18. Decay ring design

    CERN Document Server

    Chancé, A; Bouquerel, E; Hancock, S; Jensen, E

    The study of the neutrino oscillation between its different flavours needs pureand very intense fluxes of high energy, well collimated neutrinos with a welldetermined energy spectrum. A dedicated machine seems to be necessarynowadays to reach the required flux. A new concept based on the β-decayof radioactive ions which were accelerated in an accelerator chain was thenproposed. After ion production, stripping, bunching and acceleration, the unstableions are then stored in a racetrack-shaped superconducting decay ring.Finally, the ions are accumulated in the decay ring until being lost. The incomingbeam is merged to the stored beam by using a specific RF system, whichwill be presented here.We propose here to study some aspects of the decay ring, such as its opticalproperties, its RF system or the management of the losses which occur in thering (mainly by decay or by collimation).

  19. Characterization of the Fluorescence Properties of 4-Dialkylaminochalcones and Investigation of the Cytotoxic Mechanism of Chalcones.

    Science.gov (United States)

    Zhou, Bo; Jiang, Peixin; Lu, Junxuan; Xing, Chengguo

    2016-07-01

    Understanding the mechanisms responsible for the various biological activities of chalcones, particularly the direct cellular targets, presents an unmet challenge. Here, we prepared a series of fluorescent chalcone derivatives as chemical probes for their mechanistic investigation. Upon systematic physicochemical characterization, we explored their potential to elucidate the mode of action of chalcones' cytotoxicity. The fluorescence of the chalcones was found to be highly sensitive to structural and environmental factors. Structurally, a 4-dialkylamino group on the B ring, suitable electronic properties of the A ring substituents, and the planar conformation of the chalcone's core structure were essential for optimal fluorescence. Environmental factors influencing fluorescence included solvent polarity, pH, and the interactions of the chalcones with proteins and detergents. It was found that 18 chalcones showed a fluorescent brightness greater than 6000 M(-1)  cm(-1) in DMSO. However, water dramatically quenched the fluorescence, although it could be partially recovered in the presence of BSA or detergents. As expected, these fluorescent chalcones showed a sharp structure-activity relationship in their cellular cytotoxicity, leading to the identification of structurally similar cytotoxic and non-cytotoxic fluorescent chalcones as chemical probes. Confocal microscopy results revealed the co-localization of the cytotoxic probe C8 and tubulin in cells, supporting tubulin as the direct cellular target responsible for the cytotoxicity of chalcones. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    This dissertation investigates fusion rings, which are Grothendieck groups of rigid, monoidal, semisimple, abelian categories. Special interest is in rational fusion rings, i.e., fusion rings which admit a finite basis, for as commutative rings they may be presented as quotients of polynomial rings...... by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum...

  1. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina

    2012-01-01

    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from [12] and give a similar description of the sp2n-fusion ring in terms of noncommutative symmetric...... functions. Moreover we give a presentation of all fusion rings in classical types as quotients of polynomial rings. Finally we also compute the fu- sion rings for type G2....

  2. Lattices for antiproton rings

    International Nuclear Information System (INIS)

    Autin, B.

    1984-01-01

    After a description of the constraints imposed by the cooling of Antiprotons on the lattice of the rings, the reasons which motivate the shape and the structure of these machines are surveyed. Linear and non-linear beam optics properties are treated with a special amplification to the Antiproton Accumulator. (orig.)

  3. Flushing Ring for EDM

    Science.gov (United States)

    Earwood, L.

    1985-01-01

    Removing debris more quickly lowers cutting time. Operation, cutting oil and pressurized air supplied to ring placed around workpiece. Air forces oil through small holes and agitates oil as it flows over workpiece. High flow rate and agitation dislodge and remove debris. Electrical discharge removes material from workpiece faster.

  4. SXLS storage ring design

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    X-ray lithography has emerged as a strong candidate to meet the demands of ever finer linewidths on integrated circuits, particularly for linewidths less than .25 microns. Proximity printing X-ray lithography makes use of soft X-rays to shadow print an image of a mask onto a semiconductor wafer to produce integrated circuits. To generate the required X-rays in sufficient quantities to make commercial production viable, electron storage rings have been proposed as the soft X-ray sources. Existing storage rings have been used to do the initial development work and the success of these efforts has led the lithographers to request that new rings be constructed that are dedicated to X-ray lithography. As a result of a series of workshops held at BNL [10.3] which were attended by both semiconductor and accelerator scientists, the following set of zeroth order specifications' on the light and electron beam of a storage ring for X-ray lithography were developed: critical wavelength of light: λ c = 6 to 10 angstroms, white light power: P = 0.25 to 2.5 watts/mrad, horizontal collection angle per port: θ = 10 to 50 mrad, electron beam sizes: σ x ∼ σ y y ' < 1 mrad

  5. Ring Bubbles of Dolphins

    Science.gov (United States)

    Shariff, Karim; Marten, Ken; Psarakos, Suchi; White, Don J.; Merriam, Marshal (Technical Monitor)

    1996-01-01

    The article discusses how dolphins create and play with three types of air-filled vortices. The underlying physics is discussed. Photographs and sketches illustrating the dolphin's actions and physics are presented. The dolphins engage in this behavior on their own initiative without food reward. These behaviors are done repeatedly and with singleminded effort. The first type is the ejection of bubbles which, after some practice on the part of the dolphin, turn into toroidal vortex ring bubbles by the mechanism of baroclinic torque. These bubbles grow in radius and become thinner as they rise vertically to the surface. One dolphin would blow two in succession and guide them to fuse into one. Physicists call this a vortex reconnection. In the second type, the dolphins first create an invisible vortex ring in the water by swimming on their side and waving their tail fin (also called flukes) vigorously. This vortex ring travels horizontally in the water. The dolphin then turns around, finds the vortex and injects a stream of air into it from its blowhole. The air "fills-out" the core of the vortex ring. Often, the dolphin would knock-off a smaller ring bubble from the larger ring (this also involves vortex reconnection) and steer the smaller ring around the tank. One other dolphin employed a few other techniques for planting air into the fluke vortex. One technique included standing vertically in the water with tail-up, head-down and tail piercing the free surface. As the fluke is waved to create the vortex ring, air is entrained from above the surface. Another technique was gulping air in the mouth, diving down, releasing air bubbles from the mouth and curling them into a ring when they rose to the level of the fluke. In the third type, demonstrated by only one dolphin, the longitudinal vortex created by the dorsal fin on the back is used to produce 10-15 foot long helical bubbles. In one technique she swims in a curved path. This creates a dorsal fin vortex since

  6. Are diamond nanoparticles cytotoxic?

    Science.gov (United States)

    Schrand, Amanda M; Huang, Houjin; Carlson, Cataleya; Schlager, John J; Omacr Sawa, Eiji; Hussain, Saber M; Dai, Liming

    2007-01-11

    Finely divided carbon particles, including charcoal, lampblack, and diamond particles, have been used for ornamental and official tattoos since ancient times. With the recent development in nanoscience and nanotechnology, carbon-based nanomaterials (e.g., fullerenes, nanotubes, nanodiamonds) attract a great deal of interest. Owing to their low chemical reactivity and unique physical properties, nanodiamonds could be useful in a variety of biological applications such as carriers for drugs, genes, or proteins; novel imaging techniques; coatings for implantable materials; and biosensors and biomedical nanorobots. Therefore, it is essential to ascertain the possible hazards of nanodiamonds to humans and other biological systems. We have, for the first time, assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm. Assays of cell viability such as mitochondrial function (MTT) and luminescent ATP production showed that nanodiamonds were not toxic to a variety of cell types. Furthermore, nanodiamonds did not produce significant reactive oxygen species. Cells can grow on nanodiamond-coated substrates without morphological changes compared to controls. These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types.

  7. Cytotoxicity effects of alkoxy

    Directory of Open Access Journals (Sweden)

    Wan M. Khairul

    2017-05-01

    Full Text Available In this study, the effort was to design and synthesize five new members of alkoxy substituted thiourea derivatives (3a–3e featuring general formula of A-ArC(ONHC(SNHAr-D in which A represents the methoxy group and D as –OCnH2n+1 (alkoxyl group, where n = 6,7,8,9, and 10 have been successfully designed, prepared, characterized, and evaluated for anti-amoebic activities. They were spectroscopically characterized by 1H and 13C Nuclear Magnetic Resonance (NMR, Fourier Transform Infrared (FT-IR spectroscopy, and Ultraviolet–visible (UV–vis spectroscopy analysis. In turn, they were used to investigate the cytotoxicity effect on Acanthamoeba sp. at their IC50 values and membrane permeability. Compounds 3a and 3b revealed to have good activity towards Acanthamoeba sp. compared to other compounds of 3c, 3d, and 3e. The observation under fluorescence microscopy by AOPI (Acridine-orange/Propidium iodide staining indicated that treated amoeba cells by 3a–3e show loss of their membrane permeability.

  8. Cytotoxic, antibacterial and analgesic activities of Rhaphidophora glauca (Wall. Schott leaves

    Directory of Open Access Journals (Sweden)

    Mir Muhammad Nasir Uddin

    2016-09-01

    Full Text Available Objective: To investigation of cytotoxic, antimicrobial and analgesic activities of different fractions of Rhaphidophora glauca (Wall. Schott. Methods: Two partially purified aqueous methanolic fractions from ethyl acetate extract (AMF-1 and chloroform extract (AMF-2 obtained from the partitioning were used in study. The cytotoxic effect was determined by brine shrimp lethality bioassay. Antibacterial activity was investigated by disc diffusion and minimal inhibitory concentration methods. Hot plate method and acetic acid test was used for determining analgesic activity. Results: The LC50 values of AMF-1 and AMF-2 were found to be 287.73 and 428.54 µg/mL respectively, where colchicines showed LC50 of 11.16 µg/mL. The zone of inhibition of the fractions AMF-1 and AMF-2 was found to be in the range of 8–26 mm in 2 000 µg/disc, as compared to reference antibiotics kanamycin (11–28 mm at 30 µg/disc and ciprofloxacin (20–25 mm at 30 µg/disc indicating the antibacterial activity. In hot plate test, the highest pain inhibitory activity was found at a dose of 250 mg/kg for AMF-1 which was statistically significant (P ≤ 0.05 compared to both positive and negative control at 30 min interval. In acid induced model, both AMF-1 and AMF-2 at a dose of 500 mg/kg showed significant activity compared to positive and negative control. Conclusions: This study found that Rhaphidophora glauca possesses potential cytotoxic, antibacterial and analgesic activity. Further study may be needed to isolate the bioactive compounds responsible for different activities with subsequent mechanistic study.

  9. FUZZY RINGS AND ITS PROPERTIES

    Directory of Open Access Journals (Sweden)

    Karyati Karyati

    2017-01-01

      One of algebraic structure that involves a binary operation is a group that is defined  an un empty set (classical with an associative binary operation, it has identity elements and each element has an inverse. In the structure of the group known as the term subgroup, normal subgroup, subgroup and factor group homomorphism and its properties. Classical algebraic structure is developed to algebraic structure fuzzy by the researchers as an example semi group fuzzy and fuzzy group after fuzzy sets is introduced by L. A. Zadeh at 1965. It is inspired of writing about semi group fuzzy and group of fuzzy, a research on the algebraic structure of the ring is held with reviewing ring fuzzy, ideal ring fuzzy, homomorphism ring fuzzy and quotient ring fuzzy with its properties. The results of this study are obtained fuzzy properties of the ring, ring ideal properties fuzzy, properties of fuzzy ring homomorphism and properties of fuzzy quotient ring by utilizing a subset of a subset level  and strong level  as well as image and pre-image homomorphism fuzzy ring.   Keywords: fuzzy ring, subset level, homomorphism fuzzy ring, fuzzy quotient ring

  10. Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin

    Science.gov (United States)

    Gigant, B.; Cormier, A.; Dorléans, A.; Ravelli, R. B. G.; Knossow, M.

    Microtubules (MTs) are dynamic structures of the eukaryotic cytoskeleton that, during cell division, form the mitotic spindle. Perturbing them leads to mitotic arrest and ultimately to cell death. Consistently, MTs and their building block, αβ tubulin, are one of the best characterized targets in anti-cancer chemotherapy. Drugs that interfere with MTs either stabilize or destabilize them. The latter class is the subject of this review. These ligands bind to the colchicine site or to the vinca domain, two distinct sites located at a distance from each other on tubulin. Nevertheless the effects of both classes of ligands share a common theme, they prevent the formation of MT specific contacts, therefore triggering their disassembly.

  11. The Efficacy and Safety of Treatments for Acute Gout: Results from a Series of Systematic Literature Reviews Including Cochrane Reviews on Intraarticular Glucocorticoids, Colchicine, Nonsteroidal Antiinflammatory Drugs, and Interleukin-1 Inhibitors

    NARCIS (Netherlands)

    Wechalekar, Mihir D.; Vinik, Ophir; Moi, John H. Y.; Sivera, Francisca; van Echteld, Irene A. A. M.; van Durme, Caroline; Falzon, Louise; Bombardier, Claire; Carmona, Loreto; Aletaha, Daniel; Landewé, Robert B.; van der Heijde, Désirée M. F. M.; Buchbinder, Rachelle

    2014-01-01

    Objective. To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. Methods. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to

  12. Cytotoxicity of dentin bonding agents.

    Science.gov (United States)

    Cal, Ebru; Guneri, Pelin; Atay, Ayse; Cetintas, Vildan Bozok

    2014-01-01

    This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond) by XTT assay using human gingival fibroblast cells. Samples of dentin bonding agents were prepared on a black 96-well microplate, and the cytotoxicity of each bonding material was measured every 24 hours for 7 days, then on Days 14, 21, and 28. One-way ANOVA and Bonferroni post hoc tests were used for statistical analyses. All 5 materials were evaluated as severely cytotoxic (P agents showed severe cytotoxicity with viability results exception of Adper Single Bond Plus, toxicity continued to Day 28 for all compounds. The utmost care must be considered during the clinical utilization of dentin bonding agents to keep them within the area of restoration and prevent their contact with adjacent tissues.

  13. Cytotoxicity of Hymenocallis expansa alkaloids.

    Science.gov (United States)

    Antoun, M D; Mendoza, N T; Ríos, Y R; Proctor, G R; Wickramaratne, D B; Pezzuto, J M; Kinghorn, A D

    1993-08-01

    From the bulbs and leaves of Hymenocallis expansa (Amaryllidaceae), three alkaloid constituents were identified: (+)-tazettine, (+)-hippeastrine, and (-)-haemanthidine. These alkaloids demonstrated significant cytotoxicity when tested against a panel of human and murine tumor cell lines.

  14. Inorganic glass ceramic slip rings

    Science.gov (United States)

    Glossbrenner, E. W.; Cole, S. R.

    1972-01-01

    Prototypes of slip rings have been fabricated from ceramic glass, a material which is highly resistant to deterioration due to high temperature. Slip ring assemblies were not structurally damaged by mechanical tests and performed statisfactorily for 200 hours.

  15. e-læring

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    e-læring kan defineres på ganske mange måder. Ordet e-læring består jo tydeligt nok af to elementer. E + læring ligesom e-handel eller e-banking, og umiddelbart vil de fleste nok sige, at det så handler om læring vha. internettet. I bidraget advokeres for en læringsmæssig frem for normativ tilgang....

  16. Design of low energy ring(s)

    CERN Document Server

    Lachaize, Antoine

    During the last two years, several upgrades of the initial baseline scenario were studied with the aim of increasing the average intensity of ion beams in the accelerator chain of the Beta Beam complex. This is the reason why the Rapid Cycling Synchrotron (RCS) specifications were reconsidered many times [1], [2], [3].General considerations on the optical design were presented at the Beta Beam Task Meetings held at CERN and at Saclay in 2005 [4]. More detailed beam optics studies were performed during the next months. Lattices, RF system parameters, multi-turn injection scheme, fast extraction, closed orbit correction and chromaticity correction systems were proposed for different versions of the RCS [5], [6], [7].Finally, the RCS specifications have stabilized in November 2006 after the fourth Beta Beam Task Meeting when it was decided to fix the maximum magnetic rigidity of ion beams to 14.47 T.m (3.5 GeV equivalent proton energy) and to adopt a ring physical radius of 40 m in order to facilitate injectio...

  17. Clean elements in abelian rings

    Indian Academy of Sciences (India)

    equivalent to being clean for an abelian ring is 'topologically boolean'. In line with [1] we say that a ring R (not necessarily commutative) is right (resp. left) topologically boolean, or a right (resp. left) tb-ring for short, if for every pair of distinct maximal right (resp. left) ideals of R there is an idempotent in exactly one of them.

  18. Ring Confidential Transactions

    Directory of Open Access Journals (Sweden)

    Shen Noether

    2016-12-01

    Full Text Available This article introduces a method of hiding transaction amounts in the strongly decentralized anonymous cryptocurrency Monero. Similar to Bitcoin, Monero is a cryptocurrency which is distributed through a proof-of-work “mining” process having no central party or trusted setup. The original Monero protocol was based on CryptoNote, which uses ring signatures and one-time keys to hide the destination and origin of transactions. Recently the technique of using a commitment scheme to hide the amount of a transaction has been discussed and implemented by Bitcoin Core developer Gregory Maxwell. In this article, a new type of ring signature, A Multilayered Linkable Spontaneous Anonymous Group signature is described which allows one to include a Pedersen Commitment in a ring signature. This construction results in a digital currency with hidden amounts, origins and destinations of transactions with reasonable efficiency and verifiable, trustless coin generation. The author would like to note that early drafts of this were publicized in the Monero Community and on the #bitcoin-wizards IRC channel. Blockchain hashed drafts are available showing that this work was started in Summer 2015, and completed in early October 2015. An eprint is also available at http://eprint.iacr.org/2015/1098.

  19. Evaluation and SAR analysis of the cytotoxicity of tanshinones in colon cancer cells.

    Science.gov (United States)

    Wang, Lin; Liu, An; Zhang, Fei-Long; Yeung, John H K; Li, Xu-Qin; Cho, Chi-Hin

    2014-03-01

    This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action. Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM). Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells. The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  20. Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3- secretion in the pig.

    Science.gov (United States)

    Veel, T; Buanes, T; Grotmol, T; Engeland, E; Raeder, M G

    1990-08-01

    Secretin causes the bile duct cells to secrete HCO3-. To examine whether the transformation of duct cell ultrastructure that follows secretin stimulation depends on microtubules and is important for ductular HCO3- secretion, we examined the effect of colchicine on ductular HCO3- secretion and on the morphology of cells lining bile ductules of anaesthetized pigs. Colchicine blocked secretin-dependent cytoplasmic clearance of tubulovesicles and prevented expansion of the basolateral plasma membrane in duct cells and reduced the ductular HCO3- secretory response from 132 +/- 25 mumol min-1 to 97 +/- 14 mumol min-1. In contrast, lumicolchicine did not affect secretin-dependent tubulovesicle clearance or plasma membrane geometry or ductular HCO3- secretion. Accordingly, secretin-dependent cytoplasmic clearance of tubulovesicles in bile duct cells appears to depend on microtubules and to be important for ductular HCO3- secretion.

  1. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial mediterranean fever: a descriptive study

    Directory of Open Access Journals (Sweden)

    Talaat Hala Salah El-Din

    2012-12-01

    Full Text Available Abstract Background Familial Mediterranean fever (FMF is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Objective To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. Methods A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C, M680I (G/A, I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Results Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes, on only 1 allele in 40 patients (heterozygotes, and on none of the alleles (uncharacterized cases. Mild to moderate disease severity score (according to Tel Hashomer key to severity score was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0

  2. Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

    Science.gov (United States)

    Polat, Adem; Acikel, Cengizhan; Sozeri, Betul; Dursun, Ismail; Kasapcopur, Ozgur; Gulez, Nesrin; Simsek, Dogan; Saldir, Mehmet; Dokurel, Ipek; Poyrazoglu, Hakan; Bakkaloglu, Sevcan; Delibas, Ali; Ekinci, Zelal; Ayaz, Nuray A; Kandur, Yasar; Peru, Harun; Kurt, Yasemin G; Polat, Safiye R; Unsal, Erbil; Makay, Balahan; Gok, Faysal; Ozen, Seza; Demirkaya, Erkan

    2016-04-07

    In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

  3. Use of Colchicine in Cortical Area 1 of the Hippocampus Impairs Transmission of Non-Motivational Information by the Pyramidal Cells

    Directory of Open Access Journals (Sweden)

    Nosaibeh Riahi Zaniani

    2013-11-01

    Full Text Available Colchicine, a potent neurotoxin derived from plants, has been recently introduced as a degenerative toxin of small pyramidal cells in the cortical area 1 of the hippocampus (CA1. In this study, the effect of the alkaloid in CA1 on the behaviors in the conditioning task was measured. Injections of colchicine (1,5 μg/rat, intra-CA1 was performed in the male Wistar rats, while the animals were settled and cannulated in a stereotaxic apparatus. In the control group solely injection of saline (1 μl/rat, intra-CA1 was used. One week later, all the animals passed the saline conditioning task using a three-day schedule of an unbiased paradigm. They were administered saline (1 ml/kg, s.c. twice a day throughout the conditioning phase. To evaluate the possible effects of cell injury by the toxin on the pyramidal cells, both the motivational signals while in the conditioning box and the non-motivational locomotive signs of the treated and control rats were measured. Based on the present study the alkaloid caused no change in the score of place conditioning, but affected both the sniffing and grooming behaviors in the group that received colchicine. However, the alkaloid did not show the significant effect on the rearing or compartment entering in the rats. According to the findings, the intra-CA1 injection of colchicine may impair the neuronal transmission of non-motivational information by the pyramidal cells in the dorsal hippocampus.

  4. Effect of gamma-irradiation and colchicine on cell division and differentiation of xylem elements in citrus limon juice vesicle cultures

    International Nuclear Information System (INIS)

    Khan, Aysha; Chauhan, Y.S.

    1999-01-01

    The effects of varying doses of gamma irradiation on cell division and cytodifferentiation of tracheary elements in cultured juice vesicles of Citrus limon (L) Burmann var. Assam lemon were investigated. Low radiation doses stimulated cell division and differentiation of xylem fibres, sclereids and tracheids in explants given up to 10 Gy of gamma rays. Although cell division and cytodifferentiation of fibers and sclereids occurred in explants exposed to 150 dose of Gy radiation, the intensity of differentiation was much less than that induced by 10 Gy radiation dose. Amongst the differential elements, tracheids were more sensitive to radiation than fibres and sclereids. The requirement of cell division for differentiation of xylem cells was also studied by using different concentrations of colchicine in Citrus limon juice vesicle cultures. It was found that the low concentrations of colchicine permitted normal cell division and also resulted in normal differentiation of xylem cells; higher colchicine concentration, however, inhibited cell division as well as differentiation and resulted in an abnormal differentiation of tracheary element. A positive correlation between intensity of nucleic acid staining and cell division in both the above-mentioned experiments was qualitatively confirmed by Azur B staining test of nucleic acid. Thus, it was concluded that juice vesicle parenchyma cells go through nucleic acid synthesis, followed by cell division before differentiation. (author)

  5. Colchicine for the prevention of pericarditis: what we know and what we do not know in 2014 - systematic review and meta-analysis.

    Science.gov (United States)

    Imazio, Massimo; Brucato, Antonio; Belli, Riccardo; Forno, Davide; Ferro, Silvia; Trinchero, Rita; Adler, Yehuda

    2014-12-01

    The purpose of this study was to investigate and summarize available evidence on the efficacy and safety of colchicine for pericarditis prevention. Disease recurrence is the major and most common complication of pericarditis and its prevention may reduce morbidity and management costs. Colchicine has been intensively studied in the last decade for pericarditis prevention. Controlled clinical studies were searched in several databases and were included provided they focused on the pharmacologic primary or secondary prevention of pericarditis. We performed a meta-analysis including studies of primary outcome, adverse events and drug withdrawal. From the initial sample of 175 citations, seven controlled clinical trials were finally included (1275 patients): five studies were double-blind randomized controlled trials (RCT), and two studies were open-label RCTs. Trials followed patients for a mean of 19 months. Meta-analytic pooling showed that colchicine use was associated with a reduced risk of pericarditis during follow-up [odds ratio (OR) 0.33 (0.25-0.44), P for effect pericarditis without a significant increase of the risk of side-effects and drug withdrawals.

  6. SOR-ring failure

    International Nuclear Information System (INIS)

    Kitamura, Hideo

    1981-01-01

    It was in the autumn of 1976 that the SOR-ring (synchrotron radiation storage ring) has commenced the regular operation. Since then, the period when the operation was interrupted due to the failures of SOR-ring itself is in total about 8 weeks. Failures and accidents have occurred most in the vacuum system. Those failure experiences are described on the vacuum, electromagnet, radio-frequency acceleration and beam transport systems with their interrupted periods. The eleven failures in the vacuum system have been reported, such as bellows breakage in a heating-evacuating period, leakage from the bellows of straight-through valves (made in U.S.A. and Japan), and leakage from the joint flange of the vacuum system. The longest interruption was 5 weeks due to the failure of a domestically manufactured straight-through valve. The failures of the electromagnet system involve the breakage in a cooling water system, short circuit of a winding in the Q magnet power transformer, blow of a fuse protecting the deflection magnet power source by the current less than the rating, and others. The failures of the RF acceleration system include the breakage of an output electronic tube the breakage of a cavity ceramic, RF voltage fluctuation due to the contact deterioration at a cavity electrode, and the failure of grid bias power source. It is necessary to select the highly reliable components for the vacuum system because the vacuum system failures require longer time for recovery, and very likely to induce secondary and tertiary failures. (Wakatsuki, Y.)

  7. Femtoslicing in Storage Rings

    CERN Document Server

    Khan, Shaukat

    2005-01-01

    The generation of ultrashort synchrotron radiation pulses by laser-induced energy modulation of electrons and their subsequent transverse displacement, now dubbed "femtoslicing," was demonstrated at the Advanced Light Source in Berkeley. More recently, a femtoslicing user facility was commissioned at the BESSY storage ring in Berlin, and another project is in progress at the Swiss Light Source. The paper reviews the principle of femtoslicing, its merits and shortcomings, as well as the variations of its technical implementation. Various diagnostics techniques to detect successful laser-electron interaction are discussed and experimental results are presented.

  8. Proton storage rings

    International Nuclear Information System (INIS)

    Rau, R.R.

    1978-04-01

    A discussion is given of proton storage ring beam dynamic characteristics. Topics considered include: (1) beam energy; (2) beam luminosity; (3) limits on beam current; (4) beam site; (5) crossing angle; (6) beam--beam interaction; (7) longitudinal instability; (8) effects of scattering processes; (9) beam production; and (10) high magnetic fields. Much of the discussion is related to the design parameters of ISABELLE, a 400 x 400 GeV proton---proton intersecting storage accelerator to be built at Brookhaven National Laboratory

  9. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina

    2014-01-01

    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from Korff, C., Stroppel, C.: The sl(ˆn)k-WZNW fusion ring: a combinato-rial construction and a realis......We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from Korff, C., Stroppel, C.: The sl(ˆn)k-WZNW fusion ring: a combinato-rial construction...... and a realisation as quotient of quantum cohomology. Adv. Math. 225(1), 200–268, (2010) and give a similar description of the sp2n-fusion ring in terms of non-commutative symmetric functions. Moreover we give a presentation of all fusion rings in classical types as quotients of polynomial rings. Finally we also...... compute the fusion rings for type G2....

  10. Viscosity of ring polymer melts

    KAUST Repository

    Pasquino, Rossana

    2013-10-15

    We have measured the linear rheology of critically purified ring polyisoprenes, polystyrenes, and polyethyleneoxides of different molar masses. The ratio of the zero-shear viscosities of linear polymer melts η0,linear to their ring counterparts η0,ring at isofrictional conditions is discussed as a function of the number of entanglements Z. In the unentangled regime η0,linear/η 0,ring is virtually constant, consistent with the earlier data, atomistic simulations, and the theoretical expectation η0,linear/ η0,ring = 2. In the entanglement regime, the Z-dependence of ring viscosity is much weaker than that of linear polymers, in qualitative agreement with predictions from scaling theory and simulations. The power-law extracted from the available experimental data in the rather limited range 1 < Z < 20, η0,linear/η0,ring ∼ Z 1.2±0.3, is weaker than the scaling prediction (η0,linear/η0,ring ∼ Z 1.6±0.3) and the simulations (η0,linear/ η0,ring ∼ Z2.0±0.3). Nevertheless, the present collection of state-of-the-art experimental data unambiguously demonstrates that rings exhibit a universal trend clearly departing from that of their linear counterparts, and hence it represents a major step toward resolving a 30-year-old problem. © 2013 American Chemical Society.

  11. Saturn ring temperature variations with approaching ring equinox

    Science.gov (United States)

    Spilker, L.; Leyrat, C.; Flandes, A.; Altobelli, N.; Pilorz, S.; Ferrari, C.; Edgington, S.

    2009-04-01

    Cassini's Composite Infrared Spectrometer (CIRS) has acquired a wide-ranging set of thermal measurements of Saturn's main rings (A, B, C and Cassini Division) at solar elevations ranging from less than one degree to 24 degrees. At Saturn equinox in August the solar elevation angle will reach zero as the sun traverses from the south to north side of the rings. For the data acquired to date, temperatures were retrieved for the lit and unlit rings over a variety of ring geometries that include solar elevation, as well as spacecraft elevation, phase angle and local hour angle. To first order, the largest temperature changes on the lit face of the rings are driven by variations in phase angle while differences in temperature with changing spacecraft elevation and local time are a secondary effect. Decreasing ring temperature with decreasing solar elevation are observed for both the lit and unlit faces of the rings after phase angle and local time effects are taken into account. As the solar elevation continues to decrease, the ring temperatures are decreasing in a non-linear fashion. The difference in temperature between the lit and unlit sides of the rings is decreasing also with decreasing solar elevation. Using ring thermal models developed by Leyrat we extrapolate to the expected minimum ring temperatures at equinox for our planned CIRS ring observations. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA and at CEA Saclay supported by the "Programme National de Planetologie". Copyright 2009 California Institute of Technology. Government sponsorship acknowledged.

  12. Ring Image Analyzer

    Science.gov (United States)

    Strekalov, Dmitry V.

    2012-01-01

    Ring Image Analyzer software analyzes images to recognize elliptical patterns. It determines the ellipse parameters (axes ratio, centroid coordinate, tilt angle). The program attempts to recognize elliptical fringes (e.g., Newton Rings) on a photograph and determine their centroid position, the short-to-long-axis ratio, and the angle of rotation of the long axis relative to the horizontal direction on the photograph. These capabilities are important in interferometric imaging and control of surfaces. In particular, this program has been developed and applied for determining the rim shape of precision-machined optical whispering gallery mode resonators. The program relies on a unique image recognition algorithm aimed at recognizing elliptical shapes, but can be easily adapted to other geometric shapes. It is robust against non-elliptical details of the image and against noise. Interferometric analysis of precision-machined surfaces remains an important technological instrument in hardware development and quality analysis. This software automates and increases the accuracy of this technique. The software has been developed for the needs of an R&TD-funded project and has become an important asset for the future research proposal to NASA as well as other agencies.

  13. Flexible ring seal

    International Nuclear Information System (INIS)

    Abbes, Claude; Gournier, Andre; Rouaud, Christian; Villepoix, Raymond de.

    1976-01-01

    The invention concerns a flexible metal ring seal, able to ensure a perfect seal between two bearings due to the crushing and elastic deformation properties akin to similar properties in elastomers. Various designs of seal of this kind are already known, particularly a seal made of a core formed by a helical wire spring with close-wound turns and with high axial compression ratio, closed on itself and having the shape of an annulus. This wire ring is surrounded by at least one envelope having at rest the shape of a toroidal surface of which the generating circle does not close on itself. In a particular design mode, the seal in question can include, around the internal spring, two envelopes of which one in contact with the spring is composed of a low ductility elastic metal, such as mild steel or stainless steel and the other is, on the contrary, made of a malleable metal, such as copper or nickel. The first envelope evenly distributes the partial crushing of the spring, when the seal is tightened, on the second envelope which closely fits the two surfaces between which the seal operates. The stress-crushing curve characteristic of the seal comprises two separate parts, the first with a relatively sharp slope corresponds to the start of the seal compression phase, enabling at least some of these curves to reach the requisite seal threshold very quickly, then, beyond this, a second part, practically flat, where the stress is appreciably constant for a wide operating bracket [fr

  14. NRL ion ring program

    International Nuclear Information System (INIS)

    Kapetanakos, C.A.; Golden, J.; Drobot, A.; Mahaffey, R.A.; Marsh, S.J.; Pasour, J.A.

    1977-01-01

    An experiment is under way to form a storng proton ring using the 200 ka, 1.2 MeV, 50 nsec hollow proton beam recently generated at NRL. The 5 m long magnetic field configuration consists of a magnetic cusp, a compressing magnetic field, a gate field and a magnetic mirror. The midplane value of the magnetic mirror is such that the major radius of the ring will be about 10 cm. The degree of field reversal that will be achieved with 5 x 10 16 protons per pulse from the existing beam depends upon the field reversal is possible with the 600 kA proton beam that would be generated from the low inductance coaxial triode coupled to the upgraded Gamble II generator. The propagation and trapping of an intense proton beam in the experimental magnetic field configuration is investigated numerically. The results show that the self magnetic has a very pronounced effect on the dynamics of the gyrating protons

  15. On thickness of Saturn rings

    International Nuclear Information System (INIS)

    Brahic, Andre; Laques, Pierre; Lecacheux, Jean; Servan, Bernard; Despiau, Raymond; Michet, Daniel; Renard, Leopold

    1980-01-01

    Electronographic plates of Saturn were taken during the transit of the Earth through the ring plane. Observing conditions were more favorable than those prevailing in 1966. Thanks to the quality of the detectors and the telescopes, it has been possible to make a more precise photometric determination of the brightness of the ring seen edge on and to measure the brightness variation with respect to the distance to the center of the planet. Extrapolating to the case where the elevation of the Earth above the ring plane is strictly zero, we deduce an apparent photometric ring thickness equal to 1.5+-0.3 km. For an homogeneous layer of small particles colliding inelastically, theory predicts a thickness of the order of a few particles radii, i.e. a few tens of meters. The observed brightness could be explained by the E ring, the brightness of large chunks, condensations and warping of the ring [fr

  16. Real-world treatment patterns of gout patients treated with colchicine or other common treatments for gout in acute care settings: a retrospective chart review study.

    Science.gov (United States)

    Shiozawa, Aki; Cloutier, Martin; Heroux, Julie; Guerin, Annie; Wu, Eric Q; Jackson, Robert

    2015-08-01

    To describe real-world treatment patterns of patients receiving colchicine or other treatments during a gout-related emergency room or acute care facility (ER/ACF) visit. An online physician-administered questionnaire was used to collect chart data on 500 patients with a gout-related ER/ACF visit after 16 October 2009; 250 patients receiving colchicine (Colchicine Cohort) and 250 receiving NSAIDs, systemic corticosteroids, narcotics, allopurinol, febuxostat, pegloticase, probenecid, or sulfinpyrazone (Other Cohort). Patient characteristics and treatment received/prescribed during the ER/ACF visit (Period 1 [P1]), at discharge (P2), and at the first follow-up visit (P3) are reported. A total of 45 rheumatologists and 63 primary care physicians participated in the study. Patient mean age was 51 years and 74.8% were male. The most common treatments in the Other Cohort were NSAIDs (59.6%), systemic corticosteroids (45.2%), and narcotics (33.6%). The 500 patients contributed 307 distinct treatment patterns from P1 to P3. Of the 20.6% patients not prescribed a treatment in P2, 60.2% were restarted on a treatment in P3. Of the 78.6% treated patients in P2, 27.0% had a treatment adjustment (dose increase, treatment add-on, or initiation of a different gout-related treatment - not with a urate lowering therapy only) in P3; for 72.6% of these patients, physicians justified the treatment adjustment by inadequacy of the treatment for maintenance therapy, insufficient dosage, or inadequate response. In the Colchicine Cohort, 60.8% of patients were prescribed colchicine consistently from P1 to P3, while 26.8% and 17.7% of patients in the Other Cohort were prescribed consistently NSAIDs and systemic corticosteroids from P1 to P3, respectively. Specific nature of the acute gout-related symptoms or potential attack/flare during the ER/ACF visit was not recorded. Real-world clinical practice reveals a substantial number of distinct treatment patterns and frequent treatment

  17. Saturn's Rings and Associated Ring Plasma Cavity: Evidence for Slow Ring Erosion

    Science.gov (United States)

    Farrell, W. M.; Kurth, W. S.; Gurnett, D. A.; Persoon, A. M.; MacDowall, R. J.

    2017-01-01

    We re-examine the radio and plasma wave observations obtained during the Cassini Saturn orbit insertion period, as the spacecraft flew over the northern ring surface into a radial distance of 1.3 Rs (over the C-ring). Voyager era studies suggest the rings are a source of micro-meteoroid generated plasma and dust, with theorized peak impact-created plasma outflows over the densest portion of the rings (central B-ring). In sharp contrast, the Cassini Radio and Plasma Wave System (RPWS) observations identify the presence of a ring-plasma cavity located in the central portion of the B-ring, with little evidence of impact-related plasma. While previous Voyager era studies have predicted unstable ion orbits over the C- ring, leading to field-aligned plasma transport to Saturns ionosphere, the Cassini RPWS observations do not reveal evidence for such instability-created plasma fountains. Given the passive ring loss processes observed by Cassini, we find that the ring lifetimes should extend >10(exp 9) years, and that there is limited evidence for prompt destruction (loss in <100 Myrs).

  18. Caustic rings of dark matter

    International Nuclear Information System (INIS)

    Sikivie, P.

    1997-01-01

    It is shown that the infall of collisionless dark matter onto isolated galaxies produce a series of caustic rings in the halo dark matter distribution. The properties of these caustics are investigated. It is found in particular that the density profile of the caustic behaves as the inverse distance to the ring. Bumps in the rotation curve of NGC 3198 are interpreted as due to caustic rings of dark matter

  19. Acceleration of magnetized plasma rings

    International Nuclear Information System (INIS)

    Hartman, D.; Eddleman, J.; Hammer, J.H.

    1982-01-01

    One scheme is considered, acceleration of a ring between coaxial electrodes by a B/sub theta/ field as in a coaxial rail-gun. If the electrodes are conical, a ring accelerated towards the apex of the cone undergoes self-similar compression (focussing) during acceleration. Because the allowable acceleration force F/sub a/ = kappa U/sub m//R (kappa - 2 , the accelerating distance for conical electrodes is considerably shortened over that required for coaxial electrodes. In either case however, since the accelerating flux can expand as the ring moves, most of the accelerating field energy can be converted into kinetic energy of the ring leading to high efficiency

  20. Saturn's Rings Edge-on

    Science.gov (United States)

    1995-01-01

    In one of nature's most dramatic examples of 'now-you see-them, now-you-don't', NASA's Hubble Space Telescope captured Saturn on May 22, 1995 as the planet's magnificent ring system turned edge-on. This ring-plane crossing occurs approximately every 15 years when the Earth passes through Saturn's ring plane.For comparison, the top picture was taken by Hubble on December 1, 1994 and shows the rings in a more familiar configuration for Earth observers.The bottom picture was taken shortly before the ring plane crossing. The rings do not disappear completely because the edge of the rings reflects sunlight. The dark band across the middle of Saturn is the shadow of the rings cast on the planet (the Sun is almost 3 degrees above the ring plane.) The bright stripe directly above the ring shadow is caused by sunlight reflected off the rings onto Saturn's atmosphere. Two of Saturn's icy moons are visible as tiny starlike objects in or near the ring plane. They are, from left to right, Tethys (slightly above the ring plane) and Dione.This observation will be used to determine the time of ring-plane crossing and the thickness of the main rings and to search for as yet undiscovered satellites. Knowledge of the exact time of ring-plane crossing will lead to an improved determination of the rate at which Saturn 'wobbles' about its axis (polar precession).Both pictures were taken with Hubble's Wide Field Planetary Camera 2. The top image was taken in visible light. Saturn's disk appears different in the bottom image because a narrowband filter (which only lets through light that is not absorbed by methane gas in Saturn's atmosphere) was used to reduce the bright glare of the planet. Though Saturn is approximately 900 million miles away, Hubble can see details as small as 450 miles across.The Wide Field/Planetary Camera 2 was developed by the Jet Propulsion Laboratory and managed by the Goddard Spaced Flight Center for NASA's Office of Space Science.This image and other images and

  1. Integrated Ring Resonators The Compendium

    CERN Document Server

    Rabus, Dominik G

    2007-01-01

    The optical filter, which has emerged in the last few years in integrated optics, is resonator based. Ring-resonator filters do not require facets or gratings for optical feedback and are thus particularly suited for monolithic integration with other components. Ring resonators find applications not only in optical networks, but also as sensors. The required passband shape of ring resonator-filters can be custom designed by the use of configurations of various ring coupled resonators. This book describes the current state-of-the-art on these devices with respect to design, fabrication and application.

  2. ring og refleksion

    DEFF Research Database (Denmark)

    Wahlgren, B.; Rattleff, Pernille; Høyrup, S.

    State of the art inden for forskning om læring på arbejdspladsen samt gennemgang af læringsteori og refleksionsbegrebet hos Dewey, Dreyfus, Schön, Argyris, Kolb, Jarvis, Mezirow og Brookfield. Afsluttes med diskussion af syntetiseret model for læring på arbejdspladsen.......State of the art inden for forskning om læring på arbejdspladsen samt gennemgang af læringsteori og refleksionsbegrebet hos Dewey, Dreyfus, Schön, Argyris, Kolb, Jarvis, Mezirow og Brookfield. Afsluttes med diskussion af syntetiseret model for læring på arbejdspladsen....

  3. Cytotoxic glucosphingolipid from Celtis Africana.

    Science.gov (United States)

    Perveen, Shagufta; Al-Taweel, Areej Mohammad; Fawzy, Ghada Ahmed; El-Shafae, Azza Muhammed; Khan, Afsar; Proksch, Peter

    2015-05-01

    Literature survey proved the use of the powdered sun-dried bark and roots of Celtis africana for the treatment of cancer in South Africa. The aim of this study was to do further isolation work on the ethyl acetate fraction and to investigate the cytotoxic activities of the various fractions and isolated compound. Cytotoxicity of petroleum ether, chloroform, ethyl acetate, n-butanol fractions and compound 1 were tested on mouse lymphoma cell line L5178Y using the microculture tetrazolium assay. One new glucosphingolipid 1 was isolated from the aerial parts of C. africana. The structure of the new compound was determined by extensive analysis by one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. The ethyl acetate fraction and compound 1 showed strong cytotoxic activity with an EC50 value of 8.3 μg/mL and 7.8 μg/mL, respectively, compared with Kahalalide F positive control (6.3 μg/mL). This is the first report of the occurrence of a cytotoxic glucosphingolipid in family Ulmaceae.

  4. Coiffured black rings

    Science.gov (United States)

    Bena, Iosif; Ross, Simon F.; Warner, Nicholas P.

    2014-08-01

    We describe a new type of hair on supersymmetric black string and black ring solutions, which produces the largest known violation of black hole uniqueness, parameterized by an arbitrary function and hence an infinite number of continuous parameters. The new solutions can have non-trivial density profiles for the electric fields along the horizon, and yet have a geometry that is regular, although generically not infinitely differentiable, at the horizon. Both neutral and charged probes can cross the horizon without experiencing divergent forces. We also find restricted examples, parameterized by a few arbitrary continuous parameters, where the charge densities fluctuate but the metric does not and hence is completely differentiable. Our new class of solutions owes its existence to a mechanism reminiscent of the Q-ball: in the simplest examples the metric has more symmetry than the matter that supports it.

  5. Ring-constrained Join

    DEFF Research Database (Denmark)

    Yiu, Man Lung; Karras, Panagiotis; Mamoulis, Nikos

    2008-01-01

    We introduce a novel spatial join operator, the ring-constrained join (RCJ). Given two sets P and Q of spatial points, the result of RCJ consists of pairs (p, q) (where p ε P, q ε Q) satisfying an intuitive geometric constraint: the smallest circle enclosing p and q contains no other points in P, Q....... This new operation has important applications in decision support, e.g., placing recycling stations at fair locations between restaurants and residential complexes. Clearly, RCJ is defined based on a geometric constraint but not on distances between points. Thus, our operation is fundamentally different...... from the conventional distance joins and closest pairs problems. We are not aware of efficient processing algorithms for RCJ in the literature. A brute-force solution requires computational cost quadratic to input size and it does not scale well for large datasets. In view of this, we develop efficient...

  6. Phagocytosis-induced 51Cr release from activated macrophages and blood mononuclears. Effect of colchicine and antioxidants

    International Nuclear Information System (INIS)

    McGee, M.P.; Hale, A.H.

    1981-01-01

    The chromium-release test was adapted to the measurement of the cellular injury induced when activated macrophages phagocytose particulates. Macrophages obtained from rabbit lungs undergoing BCG-induced chronic inflammation released more chromium when incubated in the presence of phagocytosable particles than when incubated under resting conditions. Blood mononuclear cells, 40-60% monocytes, procured from the same BCG-injected animals, were less susceptible to phagocytosis-induced injury than the macrophages obtained from the lungs. The amount of chromium released by the activated macrophages was proportional to the number of particles present during incubation. In the presence of catalase, the amounts of chromium released by phagocytosing and resting macrophages were similar; in the presence of superoxide dismutase and cytochrome c, the amount of chromium released by phagocytosing macrophages was 13-35% less than the amount of chromium released by macrophages incubated without the antioxidants. In addition, colchicine, an inhibitor of degranulation also exerted partial inhibition of the chromium release. These results suggest that oxygen radicals and lysosomal contents contribute to the cellular injury that results from phagocytosis

  7. On separable extensions of group rings and quaternion rings

    Directory of Open Access Journals (Sweden)

    George Szeto

    1978-01-01

    Full Text Available The purposes of the present paper are (1 to give a necessary and sufficient condition for the uniqueness of the separable idempotent for a separable group ring extension RG(R may be a non-commutative ring, and (2 to give a full description of the set of separable idempotents for a quaternion ring extension RQ over a ring R, where Q are the usual quaternions i,j,k and multiplication and addition are defined as quaternion algebras over a field. We shall show that RG has a unique separable idempotent if and only if G is abelian, that there are more than one separable idempotents for a separable quaternion ring RQ, and that RQ is separable if and only if 2 is invertible in R.

  8. Synthesis, evaluation and quantitative structure-activity relationship (QSAR) analysis of Wogonin derivatives as cytotoxic agents.

    Science.gov (United States)

    Bian, Jinlei; Li, Tinghan; Weng, Tianwei; Wang, Jubo; Chen, Yu; Li, Zhiyu

    2017-02-15

    A novel series of 49 wogonin derivatives were synthesized by introducing group at 7-, 8- or B ring of wogonin. The cytotoxic activities against HepG2, A549 and BCG-823 cancer cell lines were also investigated in vitro. Several of them showed obvious cytotoxic activities and compound 3h possessed the highest potency against HepG2, A549, and BCG-823 with IC 50 values of 1.07μM, 1.74μM and 0.98μM, respectively. A quantitative structure-activity relationship (QSAR) study of these synthetic derivatives as well as wogonin indicated that high solubility and low octanol/water partition coefficient are favorable, and excessive electrostatic properties and refractivity are unfavorable for the cytotoxic activities of these wogonin derivatives. These findings and results provide a base for further investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. DELPHI's Ring Imaging Cherenkov Chamber

    CERN Multimedia

    1989-01-01

    The hundreds of mirrors around this Ring Imaging Cherenkov Chamber reflect cones of light created by fast moving particles to a detector. The velocity of a particle can be measured by the size of the ring produced on the detector. DELPHI, which ran from 1989 to 2000 on the LEP accelerator, was primarily concerned with particle identification.

  10. Caustic rings of dark matter

    OpenAIRE

    Sikivie, Pierre

    1997-01-01

    It is shown that the infall of collisionless dark matter onto isolated galaxies produces a series of caustic rings in the halo dark matter distribution. The properties of these caustics are investigated. The density profile of the caustic is derived for a specific case. Bumps in the rotation curve of NGC 3198 are interpreted as due to caustic rings of dark matter.

  11. Pyrimidine-pyridine ring interconversion

    NARCIS (Netherlands)

    Plas, van der H.C.

    2003-01-01

    This chapter discusses the pyrimidine-to-pyridine ring transformation and pyridine-to-pyrimidine ring transformation. In nucleophile-induced pyrimidine-to-pyridine rearrangements, two types of reactions can be distinguished depending on the structure of the nucleophile: (1) reactions in which the

  12. Binomial Rings: Axiomatisation, Transfer and Classification

    OpenAIRE

    Xantcha, Qimh Richey

    2011-01-01

    Hall's binomial rings, rings with binomial coefficients, are given an axiomatisation and proved identical to the numerical rings studied by Ekedahl. The Binomial Transfer Principle is established, enabling combinatorial proofs of algebraical identities. The finitely generated binomial rings are completely classified. An application to modules over binomial rings is given.

  13. Burnside Rings of Fusion Systems

    DEFF Research Database (Denmark)

    Reeh, Sune Precht

    In this thesis we study the interactions between saturated fusion systems and group actions of the underlying p-groups. For a saturated fusion system F on a finite p-group S we construct the Burnside ring of F in terms of the finite S-sets whose actions respect the structure of the fusion system...... of Burnside rings given by multiplication with the characteristic idempotent, and we show that this map is the transfer map previously constructed. Applying these results, we show that for every saturated fusion system the ring generated by all (non-idempotent) characteristic elements in the p-local double...... Burnside ring is isomorphic to the p-local Burnside ring of the fusion system, and we disprove a conjecture by Park-Ragnarsson-Stancu on the composition product of fusion systems....

  14. Ionization cooling ring for muons

    Directory of Open Access Journals (Sweden)

    R. Palmer

    2005-06-01

    Full Text Available Practical ionization cooling rings could lead to lower cost or improved performance in neutrino factory or muon collider designs. The ring modeled here uses realistic three-dimensional fields. The performance of the ring compares favorably with the linear cooling channel used in the second U.S. Neutrino Factory Study. The normalized 6D emittance of an ideal ring is decreased by a factor of approximately 240, compared with a factor of only 15 for the linear channel. We also examine such real-world effects as windows on the absorbers and rf cavities and leaving empty lattice cells for injection and extraction. For realistic conditions the ring decreases the normalized 6D emittance by a factor of 49.

  15. The fluorometric microculture cytotoxicity assay.

    Science.gov (United States)

    Lindhagen, Elin; Nygren, Peter; Larsson, Rolf

    2008-01-01

    The fluorometric microculture cytotoxicity assay (FMCA) is a nonclonogenic microplate-based cell viability assay used for measurement of the cytotoxic and/or cytostatic effect of different compounds in vitro. The assay is based on hydrolysis of the probe, fluorescein diacetate (FDA) by esterases in cells with intact plasma membranes. The assay is available as both a semiautomated 96-well plate setup and a 384-well plate version fully adaptable to robotics. Experimental plates are prepared with a small amount of drug solution and can be stored frozen. Cells are seeded on the plates and cell viability is evaluated after 72 h. The protocol described here is applicable both for cell lines and freshly prepared tumor cells from patients and is suitable both for screening in drug development and as a basis for a predictive test for individualization of anticancer drug therapy.

  16. Evaluation of ring impedance of the Photon Factory storage ring

    International Nuclear Information System (INIS)

    Kiuchi, T.; Izawa, M.; Tokumoto, S.; Hori, Y.; Sakanaka, S.; Kobayashi, M.; Kobayakawa, H.

    1992-05-01

    The loss parameters of the ducts in the Photon Factory (PF) storage ring were evaluated using the wire method and the code TBCI. Both the measurement and the calculation were done for a different bunch length (σ) ranging from 23 to 80 ps. The PF ring impedance was estimated to be |Z/n|=3.2 Ω using the broadband impedance model. The major contribution to the impedance comes from the bellows and the gate valve sections. Improvements of these components will lower the ring impedance by half. (author)

  17. Structure-cytotoxicity relationships for dietary flavonoids

    DEFF Research Database (Denmark)

    Breinholt, V.; Dragsted, L.O.

    1998-01-01

    , and taxifolin. The structural requirements for cytotoxicity in the human cell lines, however, were less clear. Reduction of the cytotoxic response of the 3',4'-hydroxylated flavonoid, quercetin, by the hydroxyl radical scavenger mannitol and the metal chelator desferozamine suggests that reactive oxygen species......The cytotoxicity of a large series of dietary flavonoids was tested in a non-tumorigenic mouse and two human cancer cell lines, using the neutral red dye exclusion assay. All compounds tested exhibited a concentration-dependent cytotoxic action in the employed cell lines. The relative cytotoxicity...... of the flavonoids, however, Tvas found to vary greatly among the different cell Lines. With a few exceptions, the investigated flavonoids were more cytotoxic to the human cancer cell lines, than the mouse cell line. The differences in cytotoxicity were accounted for in part by differences in cellular uptake...

  18. Triterpenes as Potentially Cytotoxic Compounds

    Directory of Open Access Journals (Sweden)

    Malwina Chudzik

    2015-01-01

    Full Text Available Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities.

  19. Mechanism of cytotoxicity of paraquat

    OpenAIRE

    Fukushima, Tetsuhito; Tanaka, Keiko; Lim, Heejin; Moriyama, Masaki

    2002-01-01

    Acute paraquat poisoning seems to be very complex because many possible mechanisms of paraquat cytotoxicity have been reported. Some may not be the cause of paraquat poisoning but the result or an accompanying phenomenon of paraquat action. The mechanism critical for cell damage is still unknown. Paraquat poisoning is probably a combination of several paraquat actions. Arguing which mechanism is more critical may not be important, and these clarified mechanisms should be connected and utilize...

  20. Comparative cytotoxicity of periodontal bacteria

    International Nuclear Information System (INIS)

    Stevens, R.H.; Hammond, B.F.

    1988-01-01

    The direct cytotoxicity of sonic extracts (SE) from nine periodontal bacteria for human gingival fibroblasts (HGF) was compared. Equivalent dosages (in terms of protein concentration) of SE were used to challenge HGF cultures. The cytotoxic potential of each SE was assessed by its ability to (1) inhibit HGF proliferation, as measured by direct cell counts; (2) inhibit 3H-thymidine incorporation in HGF cultures; or (3) cause morphological alterations of the cells in challenged cultures. The highest concentration (500 micrograms SE protein/ml) of any of the SEs used to challenge the cells was found to be markedly inhibitory to the HGFs by all three of the criteria of cytotoxicity. At the lowest dosage tested (50 micrograms SE protein/ml); only SE from Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Fusobacterium nucleatum caused a significant effect (greater than 90% inhibition or overt morphological abnormalities) in the HGFs as determined by any of the criteria employed. SE from Capnocytophaga sputigena, Eikenella corrodens, or Wolinella recta also inhibited cell proliferation and thymidine incorporation at this dosage; however, the degree of inhibition (5-50%) was consistently, clearly less than that of the first group of three organisms named above. The SE of the three other organisms tested (Actinomyces odontolyticus, Bacteroides intermedius, and Streptococcus sanguis) had little or no effect (0-10% inhibition) at this concentration. The data suggest that the outcome of the interaction between bacterial components and normal resident cells of the periodontium is, at least in part, a function of the bacterial species

  1. Cytotoxic Compounds from Brucea mollis

    Directory of Open Access Journals (Sweden)

    Mai Hung Thanh TUNG

    2016-09-01

    Full Text Available Ten compounds, including soulameanone (1, isobruceine B (2, 9-methoxy-canthin-6-one (3, bruceolline F (4, niloticine (5, octatriacontan-1-ol (6, bombiprenone (7, α-tocopherol (8, inosine (9, and apigenin 7-O-β-D-glucopyranoside (10, were isolated from the leaves, stems, and roots of Brucea mollis Wall. ex Kurz. Their structures were determined using one- and two-dimensional NMR spectroscopy and mass spectrometry. All compounds were evaluated for their cytotoxic activity against KB (human carcinoma of the mouth, LU-1 (human lung adenocarcinoma, LNCaP (human prostate adeno-carcinoma, and HL-60 (human promyelocytic leukemia cancer cell lines. Compound 2 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC50 values of 0.39, 0.40, 0.34, and 0.23 μg/mL, respectively. In addition, compounds 3 and 5 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC50 values around 1–4 μg/mL. Compounds 9-methoxycanthin-6-one (3 and niloticine (5 have been discovered for the first time from the Brucea genus.

  2. Comparative cytotoxicity of periodontal bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R.H.; Hammond, B.F.

    1988-11-01

    The direct cytotoxicity of sonic extracts (SE) from nine periodontal bacteria for human gingival fibroblasts (HGF) was compared. Equivalent dosages (in terms of protein concentration) of SE were used to challenge HGF cultures. The cytotoxic potential of each SE was assessed by its ability to (1) inhibit HGF proliferation, as measured by direct cell counts; (2) inhibit 3H-thymidine incorporation in HGF cultures; or (3) cause morphological alterations of the cells in challenged cultures. The highest concentration (500 micrograms SE protein/ml) of any of the SEs used to challenge the cells was found to be markedly inhibitory to the HGFs by all three of the criteria of cytotoxicity. At the lowest dosage tested (50 micrograms SE protein/ml); only SE from Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Fusobacterium nucleatum caused a significant effect (greater than 90% inhibition or overt morphological abnormalities) in the HGFs as determined by any of the criteria employed. SE from Capnocytophaga sputigena, Eikenella corrodens, or Wolinella recta also inhibited cell proliferation and thymidine incorporation at this dosage; however, the degree of inhibition (5-50%) was consistently, clearly less than that of the first group of three organisms named above. The SE of the three other organisms tested (Actinomyces odontolyticus, Bacteroides intermedius, and Streptococcus sanguis) had little or no effect (0-10% inhibition) at this concentration. The data suggest that the outcome of the interaction between bacterial components and normal resident cells of the periodontium is, at least in part, a function of the bacterial species.

  3. Decay ring status / studies

    CERN Document Server

    Chance, A

    2008-01-01

    The aim of "beta-beams" is to produce highly energetic pure electron neutrino and anti-neutrino beams coming from β-decay of radioactive ions. In CERN baseline, after accelerating, the ions 6He2+ and 18Ne10+ are stored in a racetrack-shaped-decay ring until they are lost [1]. Consequently, the injection compensates the losses which occurred between two cycles. Two main loss sources were identified: the β decay and the injection scheme. After giving the optics, we will see how to protect the magnetic elements from the decay products. The injections scheme will be then detailed with its implications. We will see that the injection process makes a collimation section in energy necessary. Since the magnetic elements are not perfect, we will take into account the magnet misalignment and the multipole defects in the dipoles. We will talk then about the closed orbit distortion due to misalignment defects and about the long-term transverse stability with the dynamic aperture.

  4. JAERI storage ring JSR

    International Nuclear Information System (INIS)

    Yokomizo, H.; Harada, S.; Yanagida, K.; Yokoyama, M.; Nagai, T.; Suzuki, Y.; Mashiko, K.; Ishizaki, N.; Tayama, H.

    1990-01-01

    A design study for a next generation 8 GeV synchrotron radiation facility is in progress in Japan, and the Japan Atomic Energy Research Institute (JAERI) and Institute of Physical and Chemical Research (RIKEN) have join forces in this project. A compact electron storage ring JSR has been under construction in the linac building in the Tokai Research Establishment of JAERI to serve for studies of various kind of accelerator technologies, examination of insertion devices and beam monitors, and training of young researchers. This paper describes the lattice design, injection system, magnets, vacuum system, RF system, control system and beam monitors and presents some operation results regarding the electron beam injection and storage. The JSR is presently in good condition concerning it's fundamental functions such as injection, storage at around 150 MeV and 300 MeV, and acceleration from 150 MeV and 300 MeV. Photon induced gas desorption is still large because the vacuum chamber has not been aged heavily by synchrotron radiation. (N.K.)

  5. Is the bell ringing?

    CERN Multimedia

    Francesco Poppi

    2010-01-01

    During the Nobel prize-winning UA1 experiment, scientists in the control room used to ring a bell if a particularly interesting event had occurred. Today, the “CMS Exotica hotline” routine produces a daily report that lists the exotic events that were recorded the day before.   Display of an event selected by the Exotica routine. Take just a very small fraction of the available data (max. 5%); define the events that you want to keep and set the parameters accordingly; run the Exotica routine and only look at the very few images that the system has selected for you. This is the recipe that a small team of CMS researchers has developed to identify the signals coming from possible new physics processes. “This approach does not replace the accurate data analysis on the whole set of data. However, it is a very fast and effective way to focus on just a few events that are potentially very interesting”, explains Maurizio Pierini (CERN), who developed the...

  6. Particle properties and processes in Uranus' rings

    Science.gov (United States)

    Esposito, L. W.; Brahic, A.; Burns, J. A.; Marouf, Essam A.

    1991-01-01

    The particle properties and processes in the Uranian rings are analyzed from Voyager observations and ground-based data. Occultation observations of the epsilon ring are interpreted to yield an effective size of the ring particles that exceeds 70 cm, a surface mass density that exceeds 80 g/sq cm, and a ring vertical thickness greater than tens of meters for solid ice particles. The particles forming the classic rings are dark and gray, with albedo of 0.014 +/-0.004. It is argued that the small amount of dust that exists in the classical rings and between the rings in bands is created by erosion of ring particles and unseen satellites resulting from collisions and micrometeoroid bombardment. As proposed for regions of the other known ring systems, new ring material can be continually created by the destruction of small moons near the rings, which may explain the youthful appearance of the Uranian rings.

  7. Cytotoxicity of alginate for orthodontic use

    Directory of Open Access Journals (Sweden)

    Matheus Melo Pithon

    2012-12-01

    Full Text Available OBJECTIVE: To evaluate the cytotoxicity of three different alginate impression materials for orthodontic use. METHODS: Three different brands of alginate were divided into three groups, namely, Group JCO (Jeltrate Chromatic Ortho, OP (Orthoprint and CO (Cavex Orthotrace. Three control groups were also included: Group C+ (positive control, consisting of detergent Tween 80; Group C- (negative control, consisting of PBS, and Group CC (cell control, consisting of cells not exposed to any material. After manipulating the materials according to the respective manufacturer instructions, samples were made with the use of silicon rings. Then the samples were immersed in Eagle's minimum essential medium (MEM for 2 minutes. The supernatants were then removed and brought into direct contact with L929 fibroblasts. After exposure to the medium, the cells were incubated for 24 hours. Then 100 µl of 0.01% neutral red dye were added. The cells were incubated again for 3 hours so that the dye could be absorbed. After this 3-hour period, the cells were fixed to perform the viable cell count, using a spectrophotometer (BioTek, Winooski, Vermont, USA at a wavelength of 492 nm. RESULTS: Statistical differences were found when Groups CC and C- were compared with the other experimental groups. Group JCO had the highest cytotoxicity, followed by Groups OP and CO. CONCLUSION: Based on the results obtained in this work, it was concluded that all alginate impression materials are potentially cytotoxic.OBJETIVO: avaliar a citotoxicidade de três diferentes alginatos de uso ortodôntico. MÉTODOS: foram avaliados três diferentes alginatos divididos em três grupos, denominados grupo JCO (Jeltrate Chromatic Ortho, OP (Orthoprint e CO (Carrex Orthotrace. Três grupos controle também participaram: controle + (C+, constituído pelo detergente celular Tween 80; controle - (C- PBS; e controle de célula (CC onde as células não foram expostas a nenhum material. Após manipula

  8. Ion Rings for Magnetic Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Greenly, John, B.

    2005-07-31

    This Final Technical Report presents the results of the program, Ion Rings for Magnetic Fusion, which was carried out under Department of Energy funding during the period August, 1993 to January, 2005. The central objective of the program was to study the properties of field-reversed configurations formed by ion rings. In order to reach this objective, our experimental program, called the Field-reversed Ion Ring Experiment, FIREX, undertook to develop an efficient, economical technology for the production of field-reversed ion rings. A field-reversed configuration (FRC) in which the azimuthal (field-reversing) current is carried by ions with gyro-radius comparable to the magnetic separatrix radius is called a field-reversed ion ring. A background plasma is required for charge neutralization of the ring, and this plasma will be confined within the ring's closed magnetic flux. Ion rings have long been of interest as the basis of compact magnetic fusion reactors, as the basis for a high-power accelerator for an inertial fusion driver, and for other applications of high power ion beams or plasmas of high energy density. Specifically, the FIREX program was intended to address the longstanding question of the contribution of large-orbit ions to the observed stability of experimental FRCs to the MHD tilt mode. Typical experimental FRCs with s {approx} 2-4, where s is the ratio of separatrix radius to ion gyro-radius, have been stable to tilting, but desired values for a fusion reactor, s > 20, should be unstable. The FIREX ring would consist of a plasma with large s for the background ions, but with s {approx} 1 for the ring ions. By varying the proportions of these two populations, the minimum proportion of large-orbit ions necessary for stability could be determined. The incorporation of large-orbit ions, perhaps by neutral-beam injection, into an FRC has been advanced for the purpose of stabilizing, heating, controlling angular momentum, and aiding the formation

  9. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

    2016-12-01

    The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

  10. Treatment of Unstable Pelvic Ring Injuries.

    Science.gov (United States)

    Kim, Weon-Yoo

    2014-06-01

    Pelvic fractures are classified according to the stability of the pelvic ring. Unlike stable pelvic fractures, which heal without complications, unstable fractures may lead to pelvic ring deformities, which cause severe complications. An orthopedic surgeon must determine the stability of the pelvic ring by radiography and physical examination of the patient in order to ensure early, prompt treatment. This article includes anatomy of the pelvic ring, classification of pelvic ring injuries, its treatment algorithm, and corresponding cases involving unstable pelvic ring injury.

  11. Distributively generated matrix near rings

    International Nuclear Information System (INIS)

    Abbasi, S.J.

    1993-04-01

    It is known that if R is a near ring with identity then (I,+) is abelian if (I + ,+) is abelian and (I,+) is abelian if (I*,+) is abelian [S.J. Abbasi, J.D.P. Meldrum, 1991]. This paper extends these results. We show that if R is a distributively generated near ring with identity then (I,+) is included in Z(R), the center of R, if (I + ,+) is included in Z(M n (R)), the center of matrix near ring M n (R). Furthermore (I,+) is included in Z(R) if (I*,+) is included in Z(M n (R)). (author). 5 refs

  12. Researches on the Piston Ring

    Science.gov (United States)

    Ehihara, Keikiti

    1944-01-01

    In internal combustion engines, steam engines, air compressors, and so forth, the piston ring plays an important role. Especially, the recent development of Diesel engines which require a high compression pressure for their working, makes, nowadays, the packing action of the piston ring far more important than ever. Though a number of papers have been published in regard to researches on the problem of the piston ring, none has yet dealt with an exact measurement of pressure exerted on the cylinder wall at any given point of the ring. The only paper that can be traced on this subject so far is Mr. Nakagawa's report on the determination of the relative distribution of pressure on the cylinder wall, but the measuring method adopted therein appears to need further consideration. No exact idea has yet been obtained as to how the obturation of gas between the piston and cylinder, the frictional resistance of the piston, and the wear of the cylinder wall are affected by the intensity and the distribution of the radial pressure of the piston ring. Consequently, the author has endeavored, by employing an apparatus of his own invention, to get an exact determination of the pressure distribution of the piston ring. By means of a newly devised ring tester, to which piezoelectricity of quartz was applied, the distribution of the radial pressure of many sample rings on the market was accurately determined. Since many famous piston rings show very irregular pressure distribution, the author investigated and achieved a manufacturing process of the piston ring which will exert uniform pressure on the cylinder wall. Temperature effects on the configuration and on the mean spring power have also been studied. Further, the tests were performed to ascertain how the gas tightness of the piston ring may be affected by the number or spring power. The researches as to the frictional resistance between the piston ring and the cylinder wall were carried out, too. The procedure of study, and

  13. SMARANDACHE NON-ASSOCIATIVE RINGS

    OpenAIRE

    Vasantha, Kandasamy

    2002-01-01

    An associative ring is just realized or built using reals or complex; finite or infinite by defining two binary operations on it. But on the contrary when we want to define or study or even introduce a non-associative ring we need two separate algebraic structures say a commutative ring with 1 (or a field) together with a loop or a groupoid or a vector space or a linear algebra. The two non-associative well-known algebras viz. Lie algebras and Jordan algebras are mainly built using a vecto...

  14. Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses

    Science.gov (United States)

    Zhang, Yan; Yang, Jingyi; Bao, Rong; Chen, Yaoqing; Zhou, Dihan; He, Benxia; Zhong, Maohua; Li, Yaoming; Liu, Fang; Li, Qiaoli; Yang, Yi; Han, Chen; Sun, Ying; Cao, Yuan; Yan, Huimin

    2011-01-01

    The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies. PMID:21935396

  15. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine.

    Directory of Open Access Journals (Sweden)

    Saurabh Bundela

    Full Text Available Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine.

  16. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    Science.gov (United States)

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  17. Unpolarized release of vaccinia virus and HIV antigen by colchicine treatment enhances intranasal HIV antigen expression and mucosal humoral responses.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol in mucosal epithelial cells (specifically Caco-2 cell layers and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.

  18. A novel colchicine-based microtubule inhibitor exhibits potent antitumor activity by inducing mitochondrial mediated apoptosis in MIA PaCa-2 pancreatic cancer cells.

    Science.gov (United States)

    Kumar, Ashok; Singh, Baljinder; Mahajan, Girish; Sharma, Parduman R; Bharate, Sandip B; Mintoo, Mubashir J; Mondhe, Dilip M

    2016-10-01

    Colchicine, an antimitotic alkaloid isolated from Colchicum autumnale, is a classical drug for treatment of gout and familial Mediterranean fever. It causes antiproliferative effects through the inhibition of microtubule formation, which leads to mitotic arrest and cell death by apoptosis. Here, we report that a novel colchicine analog, 4o (N-[(7S)-1,2,3-trimethoxy-9-oxo-10-[3-(trifluoromethyl)-4-chlorophenylamino]-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide), which exhibited potent anticancer activities both in vitro and in vivo. In this study, 4o with excellent pharmacokinetic profile and no P-gp induction liability displayed strong inhibition of proliferation against various human cancer cell lines. However, pancreatic cancer cell line MIA PaCa-2 was found to be more sensitive towards 4o and showed strong inhibition in concentration and time-dependent manner. By increasing intracellular reactive oxygen species (ROS) levels, 4o induced endoplasmic reticular stress and mitochondrial dysfunction in MIA PaCa-2 cells. Blockage of ROS production reversed 4o-induced endoplasmic reticulum (ER) stress, calcium release, and cell death. More importantly, it revealed that increased ROS generation might be an effective strategy in treating human pancreatic cancer. Further 4o treatment induced mitotic arrest, altered the expression of cell cycle-associated proteins, and disrupted the microtubules in MIA PaCa-2 cells. 4o treatment caused loss of mitochondrial membrane potential, cytochrome c release, upregulation of Bax, downregulation of Bcl-2, and cleavage of caspase-3, thereby showing activation of mitochondrial mediated apoptosis. The in vivo anticancer activity of the compound was studied using sarcoma-180 (ascitic) and leukemia (P388 lymphocytic and L1210 lymphoid) models in mice and showed promising antitumor activity with the least toxicity unlike colchicine. Such studies have hitherto not been reported. Taken together, these findings highlighted that 4o, a

  19. Deceleration of electron rings by ions

    International Nuclear Information System (INIS)

    Schumacher, U.; Hofmann, I.; Merkel, P.; Reiser, M.

    1976-02-01

    The deceleration of intense relativistic electron rings by ions created by impact ionization in the electron rings is calculated analytically and numerically. It turns out that the stopping of rings with initial axial velocities of about β 0 = 0.1 is possible under conditions that easily can be realized experimentally in the Maryland ERA. The stopping length of the electron rings, however, depends sensitively on the initial axial ring velocities β 0 (as β 0 3 ). If the method of ring deceleration by ions is used, the reproducibility of the initial ring parameters (especially that of β 0 ) should be very good to get reliable electron ring loading and acceleration. (orig.) [de

  20. Chemistry of Renieramycins. 15. Synthesis of 22-O-Ester Derivatives of Jorunnamycin A and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

    Science.gov (United States)

    Sirimangkalakitti, Natchanun; Chamni, Supakarn; Charupant, Kornvika; Chanvorachote, Pithi; Mori, Nanae; Saito, Naoki; Suwanborirux, Khanit

    2016-08-26

    Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was evaluated. Preliminary study of the structure-cytotoxicity relationship revealed that the ester part containing a nitrogen-heterocyclic ring elevated the cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl) ester 6a is the most potent compound (IC50 1.1 and 1.6 nM), exhibiting 21-fold and 5-fold increases in cytotoxicity against the H292 and H460 NSCLC cell lines, respectively, relative to renieramycin M (1), the major cytotoxic bistetrahydroisoquinolinequinone alkaloid of the Thai blue sponge Xestospongia sp.

  1. Minimal Gromov-Witten rings

    International Nuclear Information System (INIS)

    Przyjalkowski, V V

    2008-01-01

    We construct an abstract theory of Gromov-Witten invariants of genus 0 for quantum minimal Fano varieties (a minimal class of varieties which is natural from the quantum cohomological viewpoint). Namely, we consider the minimal Gromov-Witten ring: a commutative algebra whose generators and relations are of the form used in the Gromov-Witten theory of Fano varieties (of unspecified dimension). The Gromov-Witten theory of any quantum minimal variety is a homomorphism from this ring to C. We prove an abstract reconstruction theorem which says that this ring is isomorphic to the free commutative ring generated by 'prime two-pointed invariants'. We also find solutions of the differential equation of type DN for a Fano variety of dimension N in terms of the generating series of one-pointed Gromov-Witten invariants

  2. Autumn study on storage rings

    CERN Multimedia

    1974-01-01

    The first two weeks of October have seen storage ring people from accelerator Laboratories throughout the world at CERN to study the fundamental problems of very high energy protonproton colliding beam machines.

  3. Quasi-isochronous storage rings

    International Nuclear Information System (INIS)

    Robin, D.; Forest, E.; Pellegrini, C.; Amiry, A.

    1993-01-01

    A study is made of the single-particle dynamics of an electron-positron storage ring where the phase-slip factor is made small in order to make the ring nearly isochronous and reduce the bunch length. What is found is that a quasi-isochronous ring makes it possible to obtain a bunch length in the millimeter range, about one order of magnitude shorter than present values. In this study we have extended the work of others on isochronous storage rings by quantitatively including higher-order terms in the longitudinal equations of motion. Scaling laws are then derived relating the linear term with the next-highest-order term. These scaling laws, which are derived from a two-dimensional Hamiltonian (one dimension of position and one of momentum), establish criteria for stability. These scaling laws are then checked with full six-dimensional tracking on one particular lattice

  4. ring i familien

    DEFF Research Database (Denmark)

    Kryger, Niels

    2015-01-01

    Artiklen diskutere de senere års eksplosionsagtig interesse for børns læring i familien, og sætter et kritisk lys på den snævre investeringslogik (læring skal give afkast i form af økonomisk produktivitet), der har ledsaget mange af de programmer, der er sat i gang for at fremme denne ”familielær......Artiklen diskutere de senere års eksplosionsagtig interesse for børns læring i familien, og sætter et kritisk lys på den snævre investeringslogik (læring skal give afkast i form af økonomisk produktivitet), der har ledsaget mange af de programmer, der er sat i gang for at fremme denne...

  5. Ring lasers - a brief history

    Science.gov (United States)

    Klein, Tony

    2017-10-01

    Used these days in inertial navigation, ring lasers are also used in recording the tiniest variations in the Earth's spin, as well in detecting earthquakes and even the drift of continents. How did it all begin?

  6. Prototype moving-ring reactor

    International Nuclear Information System (INIS)

    Smith, A.C. Jr.; Ashworth, C.P.; Abreu, K.E.

    1982-01-01

    We have completed a design of the Prototype Moving-Ring Reactor. The fusion fuel is confined in current-carrying rings of magnetically-field-reversed plasma (Compact Toroids). The plasma rings, formed by a coaxial plasma gun, undergo adiabatic magnetic compression to ignition temperature while they are being injected into the reactor's burner section. The cylindrical burner chamber is divided into three burn stations. Separator coils and a slight axial guide field gradient are used to shuttle the ignited toroids rapidly from one burn station to the next, pausing for 1/3 of the total burn time at each station. D-T- 3 He ice pellets refuel the rings at a rate which maintains constant radiated power

  7. The Composition of Saturn's Rings

    Science.gov (United States)

    Clark, R. N.; Cuzzi, J.; Filacchione, G.; Cruikshank, D. P.; Curchin, J. M.; Hoefen, T. M.; Nicholson, P. D.; Hedman, M.; Brown, R. H.; Buratti, B. J.; Baines, K. H.; Nelson, R. M.

    2008-12-01

    The Cassini spacecraft has obtained a unique collection of data about Saturn's rings, as it has observed the rings from 0 to 180 degrees in phase angle, and on both lit and unlit sides. Identification of trace contaminants, especially organic compounds, requires that spectra of the rings be uncontaminated by light from Saturn. The Cassini Visual and Infrared Mapping Spectrometer (VIMS) has acquired 0.35 to 5.1 micron, high spatial resolution spectroscopic data near the shadow of Saturn on the rings where scattered light is at a minimum. At low phase angles, the ring spectra show classic crystalline-ice spectral features except for a contaminant causing a UV absorption. VIMS spectra at 180-degree phase angle are generally flat, with only a weak positive feature at 2.86 microns in spectra of the F-ring. The general transmission decrease is due to large ring particles completely blocking light. The 2.86-micron feature indicates the presence of fine ice dust, where the ice's index of refraction is near 1.0, and light is not refracted or diffracted. There are no indications of interparticle scattering in the VIMS data at any phase angle. The lack of interparticle scattering indicates that the dense A and B rings must be very thin, approaching a monolayer, but rigorous constraints have yet to be modeled. Previous studies used tholins and amorphous carbon for the contaminant causing the UV absorption, but these models display additional absorptions and spectral structure in the near infrared not seen in VIMS data. Clark et al. (Icarus, v193, p372, 2008) modeled the changing blue peak and UV absorber observed on Phoebe, Iapetus, Hyperion, and Dione with amorphous carbon and nano-sized hematite. Nanohematite has muted spectral features compared to larger grained hematite, due to crystal field effects at the surfaces of small grains. Nanohematite has a strong UV absorber that matches the steep UV slope observed in spectra of Saturn's rings and has no strong IR absorptions

  8. Collector ring project at FAIR

    International Nuclear Information System (INIS)

    Dolinskii, A; Blell, U; Dimopoulou, C; Gorda, O; Leibrock, H; Litvinov, S; Laier, U; Schurig, I; Weinrich, U; Berkaev, D; Koop, I; Starostenko, A; Shatunov, P

    2015-01-01

    The collector ring is a dedicated ring for fast cooling of ions coming from separators at the FAIR project. To accommodate optimal technical solutions, a structure of a magnet lattice was recently reviewed and modified. Consequently, more appropriate technical solutions for the main magnets could be adopted. A general layout and design of the present machine is shown. The demanding extraction schemes have been detailed and open design issues were completed. (paper)

  9. Synlig læring

    DEFF Research Database (Denmark)

    Brandsen, Mads

    2017-01-01

    Introduktionen af John Hatties synlig læring i den danske skoleverden møder stadig meget kritik. Mange lærere og pædagoger oplever synlig læring som en tornado, der vil opsuge og ødelægge deres særlige danske udgave af den kontinentale dannelsestænkning, didaktik og pædagogik. Spørgsmålet er om...

  10. MUON STORAGE RINGS - NEUTRINO FACTORIES

    International Nuclear Information System (INIS)

    PARSA, Z.

    2000-01-01

    The concept of a muon storage ring based Neutrino Source (Neutrino Factory) has sparked considerable interest in the High Energy Physics community. Besides providing a first phase of a muon collider facility, it would generate more intense and well collimated neutrino beams than currently available. The BNL-AGS or some other proton driver would provide an intense proton beam that hits a target, produces pions that decay into muons. The muons must be cooled, accelerated and injected into a storage ring with a long straight section where they decay. The decays occurring in the straight sections of the ring would generate neutrino beams that could be directed to detectors located thousands of kilometers away, allowing studies of neutrino oscillations with precisions not currently accessible. For example, with the neutrino source at BNL, detectors at Soudan, Minnesota (1,715 km), and Gran Sasso, Italy (6,527 km) become very interesting possibilities. The feasibility of constructing and operating such a muon-storage-ring based Neutrino-Factory, including geotechnical questions related to building non-planar storage rings (e.g. at 8degree angle for BNL-Soudan, and 3degree angle for BNL-Gran Sasso) along with the design of the muon capture, cooling, acceleration, and storage ring for such a facility is being explored by the growing Neutrino Factory and Muon Collider Collaboration (NFMCC). The authors present overview of Neutrino Factory concept based on a muon storage ring, its components, physics opportunities, possible upgrade to a full muon collider, latest simulations of front-end, and a new bowtie-muon storage ring design

  11. Optofluidic ring resonator dye lasers

    Science.gov (United States)

    Sun, Yuze; Suter, Jonathan D.; Fan, Xudong

    2010-02-01

    We overview the recent progress on optofluidic ring resonator (OFRR) dye lasers developed in our research group. The fluidics and laser cavity design can be divided into three categories: capillary optofluidic ring resonator (COFRR), integrated cylindrical optofluidic ring resonator (ICOFRR), and coupled optofluidic ring resonator (CpOFRR). The COFRR dye laser is based on a micro-sized glass capillary with a wall thickness of a few micrometers. The capillary circular cross-section forms the ring resonator and supports the whispering gallery modes (WGMs) that interact evanescently with the gain medium in the core. The laser cavity structure is versatile to adapt to the gain medium of any refractive index. Owing to the high Q-factor (>109), the lasing threshold of 25 nJ/mm2 is achieved. Besides directly pump the dye molecules, lasing through fluorescence resonance energy transfer (FRET) between the donor and acceptor dye molecules is also studied in COFRR laser. The energy transfer process can be further controlled by designed DNA scaffold labeled with donor/acceptor molecules. The ICOFRR dye laser is based on a cylindrical ring resonator fused onto the inner surface of a thick walled glass capillary. The structure has robust mechanical strength to sustain rapid gain medium circulation. The CpOFRR utilizes a cylindrical ring resonator fused on the inner surface of the COFRR capillary. Since the capillary wall is thin, the individual WGMs of the cylindrical ring resonator and the COFRR couples strongly and forms Vernier effect, which provides a way to generate a single mode dye laser.

  12. Resonance capture and Saturn's rings

    International Nuclear Information System (INIS)

    Patterson, C.W.

    1986-05-01

    We have assigned the resonances apparently responsible for the stabilization of the Saturn's shepherd satellites and for the substructure seen in the F-ring and the ringlets in the C-ring. We show that Saturn's narrow ringlets have a substructure determined by three-body resonances with Saturn's ringmoons and the sun. We believe such resonances have important implications to satellite formation. 17 refs., 1 fig., 1 tab

  13. Ring insertions as light sources

    International Nuclear Information System (INIS)

    Green, G.K.

    1975-01-01

    Bending magnets can be inserted in the long straight sections of electron storage rings to produce synchrotron radiation. If the design is carefully proportioned, the bending magnets create only a small perturbation of the properties of the ring. The resulting spectra have favorable optical properties as sources for spectroscopy and diffraction studies. The characteristics of the source are discussed, and the geometrical requirements of the magnets are presented

  14. Commuting Π-regular rings

    Directory of Open Access Journals (Sweden)

    Shervin Sahebi

    2014-05-01

    Full Text Available ‎$R$ is called commuting regular ring (resp‎. ‎semigroupif‎ for each $x,y\\in R$ there exists $a\\in R$‎ such that$xy=yxayx$‎. ‎In this paper‎, ‎we introduce the concept of‎‎commuting $\\pi$-regular rings (resp‎. ‎semigroups and‎‎study various properties of them.

  15. The Circular RFQ Storage Ring

    International Nuclear Information System (INIS)

    Ruggiero, A. G.

    1999-01-01

    This paper presents a novel idea of storage ring for the accumulation of intense beams of light and heavy ions at low energy. The new concept is a natural development of the combined features of conventional storage rings and ion traps, and is basically a linear RFQ bent on itself. The advantages are: smaller beam dimensions, higher beam intensity, and a more compact storage device

  16. Standard Fibre Optic Ring LANs

    Science.gov (United States)

    Beale, N. C. L.

    1985-08-01

    The paper begins with a reminder of the particular need for standards in LANs. We then describe the requirements of High Integrity LANs. Current developments in LAN standards are then outlined. It is argued that the requirements of industrial LANs lead ideally to reconfiguring fibre optic rings, for which there are two major emerging standards. These two (IEEE 802.5 and ANSI FDDI) and the Cambridge Ring are discussed and compared. One implementation - the HILAN is discussed.

  17. Of Rings and Volcanoes

    Science.gov (United States)

    2002-01-01

    Office National d'Etudes et de Recherches Aérospatiales (ONERA) , Laboratoire d'Astrophysique de Grenoble (LAOG) and the DESPA and DASGAL laboratories of the Observatoire de Paris in France, in collaboration with ESO. The CONICA infra-red camera was built, under an ESO contract, by the Max-Planck-Institut für Astronomie (MPIA) (Heidelberg) and the Max-Planck Institut für Extraterrestrische Physik (MPE) (Garching) in Germany, in collaboration with ESO. Saturn - Lord of the rings ESO PR Photo 04a/02 ESO PR Photo 04a/02 [Preview - JPEG: 460 x 400 pix - 54k] [Normal - JPEG: 1034 x 800 pix - 200k] Caption : PR Photo 04a/02 shows the giant planet Saturn, as observed with the VLT NAOS-CONICA Adaptive Optics instrument on December 8, 2001; the distance was 1209 million km. It is a composite of exposures in two near-infrared wavebands (H and K) and displays well the intricate, banded structure of the planetary atmosphere and the rings. Note also the dark spot at the south pole at the bottom of the image. One of the moons, Tethys, is visible as a small point of light below the planet. It was used to guide the telescope and to perform the adaptive optics "refocussing" for this observation. More details in the text. Technical information about this photo is available below. This NAOS/CONICA image of Saturn ( PR Photo 04a/02 ), the second-largest planet in the solar system, was obtained at a time when Saturn was close to summer solstice in the southern hemisphere. At this moment, the tilt of the rings was about as large as it can be, allowing the best possible view of the planet's South Pole. That area was on Saturn's night side in 1982 and could therefore not be photographed during the Voyager encounter. The dark spot close to the South Pole is a remarkable structure that measures approximately 300 km across. It was only recently observed in visible light from the ground with a telescope at the Pic du Midi Observatory in the Pyrenees (France) - this is the first infrared image to

  18. Cytotoxic Compounds from Aloe megalacantha

    Directory of Open Access Journals (Sweden)

    Negera Abdissa

    2017-07-01

    Full Text Available Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1, aloesaponarin III (2, 10-O-methylchrysalodin (3 and methyl-26-O-feruloyl-oxyhexacosanate (4—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC50 = 0.98 µM being the most active compound.

  19. A modified short-term cytotoxicity test

    International Nuclear Information System (INIS)

    Rees, R.C.; Platts, A.A.

    1983-01-01

    Using whole blood from normal subjects, the authors have observed natural killing of K562 cells in a 4 h 51 Cr-release assay comparable with that shown by separated PBMC and whole blood depleted of serum components. Separated plasma was not toxic towards K562 targets, and failed to potentiate the level of PBMC cytotoxicity through ADCC. The presence of red blood cells did not influence natural killing. The natural cytotoxicity of whole blood was augmented by interferon and depressed by prostaglandins E1 and E2. Studies with appropriate control blood fractions show that cytotoxicity tests with whole blood provide results reflecting natural cell-mediated cytotoxicity. (Auth.)

  20. Rhythmic ring-ring stacking drives the circadian oscillator clockwise.

    Science.gov (United States)

    Chang, Yong-Gang; Tseng, Roger; Kuo, Nai-Wei; LiWang, Andy

    2012-10-16

    The oscillator of the circadian clock of cyanobacteria is composed of three proteins, KaiA, KaiB, and KaiC, which together generate a self-sustained ∼24-h rhythm of phosphorylation of KaiC. The mechanism propelling this oscillator has remained elusive, however. We show that stacking interactions between the CI and CII rings of KaiC drive the transition from the phosphorylation-specific KaiC-KaiA interaction to the dephosphorylation-specific KaiC-KaiB interaction. We have identified the KaiB-binding site, which is on the CI domain. This site is hidden when CI domains are associated as a hexameric ring. However, stacking of the CI and CII rings exposes the KaiB-binding site. Because the clock output protein SasA also binds to CI and competes with KaiB for binding, ring stacking likely regulates clock output. We demonstrate that ADP can expose the KaiB-binding site in the absence of ring stacking, providing an explanation for how it can reset the clock.

  1. Accretion in Saturn's F Ring

    Science.gov (United States)

    Meinke, B. K.; Esposito, L. W.; Stewart, G.

    2012-12-01

    Saturn's F ring is the solar system's principal natural laboratory for direct observation of accretion and disruption processes. The ring resides in the Roche zone, where tidal disruption competes with self-gravity, which allows us to observe the lifecycle of moonlets. Just as nearby moons create structure at the B ring edge (Esposito et al. 2012) and the Keeler gap (Murray 2007), the F ring "shepherding" moons Prometheus and Pandora stir up ring material and create observably changing structures on timescales of days to decades. In fact, Beurle et al (2010) show that Prometheus makes it possible for "distended, yet gravitationally coherent clumps" to form in the F ring, and Barbara and Esposito (2002) predicted a population of ~1 km bodies in the ring. In addition to the observations over the last three decades, the Cassini Ultraviolet Imaging Spectrograph (UVIS) has detected 27 statistically significant features in 101 occultations by Saturn's F ring since July 2004. Seventeen of those 27 features are associated with clumps of ring material. Two features are opaque in occultation, which makes them candidates for solid objects, which we refer to as Moonlets. The 15 other features partially block stellar signal for 22 m to just over 3.7 km along the radial expanse of the occultation. Upon visual inspection of the occultation profile, these features resemble Icicles, thus we will refer to them as such here. The density enhancements responsible for such signal attenuations are likely due to transient clumping of material, evidence that aggregations of material are ubiquitous in the F ring. Our lengthy observing campaign reveals that Icicles are likely transient clumps, while Moonlets are possible solid objects. Optical depth is an indicator of clumping because more-densely aggregated material blocks more light; therefore, it is natural to imagine moonlets as later evolutionary stage of icicle, when looser clumps of material compact to form a feature that appears

  2. Double acting stirling engine piston ring

    Science.gov (United States)

    Howarth, Roy B.

    1986-01-01

    A piston ring design for a Stirling engine wherein the contact pressure between the piston and the cylinder is maintained at a uniform level, independent of engine conditions through a balancing of the pressure exerted upon the ring's surface and thereby allowing the contact pressure on the ring to be predetermined through the use of a preloaded expander ring.

  3. Manipulation of vortex rings for flow control

    International Nuclear Information System (INIS)

    Toyoda, Kuniaki; Hiramoto, Riho

    2009-01-01

    This paper reviews the dynamics of vortex rings and the control of flow by the manipulation of vortex rings. Vortex rings play key roles in many flows; hence, the understanding of the dynamics of vortex rings is crucial for scientists and engineers dealing with flow phenomena. We describe the structures and motions of vortex rings in circular and noncircular jets, which are typical examples of flows evolving into vortex rings. For circular jets the mechanism of evolving, merging and breakdown of vortex rings is described, and for noncircular jets the dynamics of three-dimensional deformation and interaction of noncircular vortex rings under the effect of self- and mutual induction is discussed. The application of vortex-ring manipulation to the control of various flows is reviewed with successful examples, based on the relationship between the vortex ring dynamics and the flow properties. (invited paper)

  4. Structure and dynamics of ringed galaxies

    International Nuclear Information System (INIS)

    Buta, R.J.

    1984-01-01

    In many spiral and SO galaxies, single or multiple ring structures are visible in the disk. These inner rings (r), outer rings (R), and nuclear rings (nr) were investigated by means of morphology, photometry, and spectroscopy in order to provide basic data on a long neglected phenomenon. The metric properties of each ring are investigated and found to correlate with the structure of the parent galaxy. When properly calibrated, inner rings in barred (SB) systems can be used as geometric extragalactic distance indicators to distances in excess of 100 Mpc. Other statistics are presented that confirm previous indications that the rings have preferred shapes, relative sizes, and orientations with respect to bars. A survey is made of the less homogeneous non-barred (SA) ringed systems, and the causes of the inhomogeneity are isolated. It is shown that rings can be identified in multiple-ring SA systems that are exactly analogous to those in barred spirals

  5. IsoCombretaQuinazolines: Potent Cytotoxic Agents with Antitubulin Activity.

    Science.gov (United States)

    Soussi, Mohamed Ali; Provot, Olivier; Bernadat, Guillaume; Bignon, Jérome; Desravines, Déborah; Dubois, Joëlle; Brion, Jean-Daniel; Messaoudi, Samir; Alami, Mouad

    2015-08-01

    A series of novel isocombretaquinazolines (isoCoQ) 4 were quickly prepared by coupling N-toluenesulfonylhydrazones with 4-chloroquinazolines under palladium catalysis. These compounds, which can be regarded as isocombretastatin A-4 (isoCA-4) analogues that lack the 3,4,5-trimethoxyphenyl ring, displayed nanomolar-level cytotoxicity against various human cancer cell lines and were observed to effectively inhibit tubulin polymerization. The isoCoQ compounds 2-methoxy-5-(1-(2-methylquinazolin-4-yl)vinyl)phenol (4 b), 4-[1-(3-fluoro-4-methoxyphenyl)vinyl]-2-methylquinazoline (4 c), and 2-methoxy-5-(1-(2-methylquinazolin-4-yl)vinyl)aniline (4 d), which respectively bear the greatest resemblance to isoCA-4, isoFCA-4, and isoNH2 CA-4, are able to arrest HCT116 cancer cells in the G2 /M cell-cycle phase at very low concentrations. Preliminary in vitro antivascular assay results show that 4 d is able to disrupt a network of capillary-like structures formed by human umbilical vein endothelial cells on Matrigel. All these results clearly demonstrate that replacement of the 3,4,5-trimethoxyphenyl ring of isoCA-4 with a quinazoline nucleus is a feasible approach toward new and highly promising derivatives with the potential for further development as antitubulin agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Treatment of Unstable Pelvic Ring Injuries

    OpenAIRE

    Kim, Weon-Yoo

    2014-01-01

    Pelvic fractures are classified according to the stability of the pelvic ring. Unlike stable pelvic fractures, which heal without complications, unstable fractures may lead to pelvic ring deformities, which cause severe complications. An orthopedic surgeon must determine the stability of the pelvic ring by radiography and physical examination of the patient in order to ensure early, prompt treatment. This article includes anatomy of the pelvic ring, classification of pelvic ring injuries, its...

  7. Ring wormholes via duality rotations

    Directory of Open Access Journals (Sweden)

    Gary W. Gibbons

    2016-09-01

    Full Text Available We apply duality rotations and complex transformations to the Schwarzschild metric to obtain wormhole geometries with two asymptotically flat regions connected by a throat. In the simplest case these are the well-known wormholes supported by phantom scalar field. Further duality rotations remove the scalar field to yield less well known vacuum metrics of the oblate Zipoy–Voorhees–Weyl class, which describe ring wormholes. The ring encircles the wormhole throat and can have any radius, whereas its tension is always negative and should be less than −c4/4G. If the tension reaches the maximal value, the geometry becomes exactly flat, but the topology remains non-trivial and corresponds to two copies of Minkowski space glued together along the disk encircled by the ring. The geodesics are straight lines, and those which traverse the ring get to the other universe. The ring therefore literally produces a hole in space. Such wormholes could perhaps be created by negative energies concentrated in toroidal volumes, for example by vacuum fluctuations.

  8. Dream of Isochronous Ring Again

    CERN Document Server

    Hama, H

    2005-01-01

    More than 20 years ago, D.A.G. Deacon proposed an isochronous storage ring for FEL to avoid bunch heating and decreasing instantaneous gain [1]. Some of low momentum compaction (alpha) operations have been carried out, and recently coherent infrared radiation are observed on a 3rd generation light source. Because the 3rd generation rings are optimized to obtain very low emittance beam, the dispersion function in the arc sections are much reduced by introducing large bending radius, so that those are very big machines. Meanwhile N.A. Vinokurov et al. recently proposed a ring type SASE FEL based on a complete isochronous bending transport [2]. At least, experimental and theoretical study of the isochronous ring so far suggests nonlinear effects resulted from higher order dispersion and chromaticity declines the "complete" isochronous system. On the other hand, in a wavelength region of THz, tolerance of the path length along a turn of the ring seems to be within our reach. A concept to preserve of a form factor...

  9. Primitivity and weak distributivity in near rings and matrix near rings

    International Nuclear Information System (INIS)

    Abbasi, S.J.

    1993-08-01

    This paper shows the structure of matrix near ring constructed over a weakly distributive and primative near ring. It is proved that a weakly distributive primitive near ring is a ring and the matrix near rings constructed over it is also a bag. (author). 14 refs

  10. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Science.gov (United States)

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  11. Synthesis, characterisation, nuclease and cytotoxic activity of ...

    Indian Academy of Sciences (India)

    Complexes 1 and 2 were evaluated for their nuclease and in vitro anti-tumor activities against human breast and colorectal cancer cell lines. The DNA cleavage and cytotoxic assays revealed that both 1 and 2 are effective in cleaving DNA, while the cytotoxic activity of 1 is better than 2 in both human colon and breast cancer ...

  12. Cytotoxic sesquiterpene lactones from Inula britannica.

    Science.gov (United States)

    Park, E J; Kim, J

    1998-12-01

    Cytotoxicity-guided fractionation of the flowers of Inula britannica led to the isolation of four sesquiterpene lactones, 4 alpha, 6 alpha-dihydroxyeudesman-8 beta, 12-olide (1), ergolide (2), 8-epi-helenalin (3), and bigelovin (4). Compound 1 was isolated as a new natural product. These compounds showed cytotoxicity against human tumor cell lines.

  13. Proton storage ring summer workshop

    International Nuclear Information System (INIS)

    Lawrence, G.P.; Cooper, R.K.

    1977-10-01

    During the week of August 16, 1976 a Workshop was held at the Los Alamos Scientific Laboratory (LASL) on the Proton Storage Ring (PSR) for the Weapons Neutron Research Facility (WNRF). Written contributions were solicited from each of the participants in the Workshop, and the contributions that were received are presented. The papers do not represent polished or necessarily complete work, but rather represent ''first cuts'' at their respective areas. Topics covered include: (1) background information on the storage ring; (2) WNRF design; (3) rf transient during filling; (4) rf capture; (5) beam bunch compression; (6) transverse space charge limits; (7) transverse resistive instability in the PSR; (8) longitudinal resistive instability; (9) synchrotron frequency splitting; (10) E Quintus Unum--off resonance; (11) first harmonic bunching in the storage ring; (12) kicker considerations; (13) beam extraction; (14) ferrite kicker magnets; and (15) E Quintus Unum: a possible ejection scheme

  14. Adiabatic compression of ion rings

    International Nuclear Information System (INIS)

    Larrabee, D.A.; Lovelace, R.V.

    1982-01-01

    A study has been made of the compression of collisionless ion rings in an increasing external magnetic field, B/sub e/ = zB/sub e/(t), by numerically implementing a previously developed kinetic theory of ring compression. The theory is general in that there is no limitation on the ring geometry or the compression ratio, lambdaequivalentB/sub e/ (final)/B/sub e/ (initial)> or =1. However, the motion of a single particle in an equilibrium is assumed to be completely characterized by its energy H and canonical angular momentum P/sub theta/ with the absence of a third constant of the motion. The present computational work assumes that plasma currents are negligible, as is appropriate for a low-temperature collisional plasma. For a variety of initial ring geometries and initial distribution functions (having a single value of P/sub theta/), it is found that the parameters for ''fat'', small aspect ratio rings follow general scaling laws over a large range of compression ratios, 1 3 : The ring radius varies as lambda/sup -1/2/; the average single particle energy as lambda/sup 0.72/; the root mean square energy spread as lambda/sup 1.1/; and the total current as lambda/sup 0.79/. The field reversal parameter is found to saturate at values typically between 2 and 3. For large compression ratios the current density is found to ''hollow out''. This hollowing tends to improve the interchange stability of an embedded low β plasma. The implications of these scaling laws for fusion reactor systems are discussed

  15. Tree rings and radiocarbon calibration

    International Nuclear Information System (INIS)

    Barbetti, M.

    1999-01-01

    Only a few kinds of trees in Australia and Southeast Asia are known to have growth rings that are both distinct and annual. Those that do are therefore extremely important to climatic and isotope studies. In western Tasmania, extensive work with Huon pine (Lagarostrobos franklinii) has shown that many living trees are more than 1,000 years old, and that their ring widths are sensitive to temperature, rainfall and cloud cover (Buckley et al. 1997). At the Stanley River there is a forest of living (and recently felled) trees which we have sampled and measured. There are also thousands of subfossil Huon pine logs, buried at depths less than 5 metres in an area of floodplain extending over a distance of more than a kilometre with a width of tens of metres. Some of these logs have been buried for 50,000 years or more, but most of them belong to the period between 15,000 years and the present. In previous expeditions in the 1980s and 1990s, we excavated and sampled about 350 logs (Barbetti et al. 1995; Nanson et al. 1995). By measuring the ring-width patterns, and matching them between logs and living trees, we have constructed a tree-ring dated chronology from 571 BC to AD 1992. We have also built a 4254-ring floating chronology (placed by radiocarbon at ca. 3580 to 7830 years ago), and an earlier 1268-ring chronology (ca. 7,580 to 8,850 years ago). There are many individuals, or pairs of logs which match and together span several centuries, at 9,000 years ago and beyond

  16. Cytotoxicity study of pyrazole derivatives

    Directory of Open Access Journals (Sweden)

    Nusrat Binta Ahasan

    2007-06-01

    Full Text Available Pyrazolone heterocyclic compound, 3-methyl-1-phenyl-2-pyrazoline-5-one 2(a was synthesized by condensation reaction between ethyl acetoacetate and phenyl hydrazine and was converted into their corresponding heterocyclic derivatives 2(b to 2(f2 . Their cytotoxicity effects were measured by brine shrimp lethality bioassay. Among them the compounds 2(b , 2(f1 , and 2(f2 were highly active according to IC50 values 19.50, 19.50 and 20 ppm respectively. The rest of compounds 2(a , 2(c , 2(d1 , and 2(d2 having IC50 values 38, 33.50, 37.50, 36, 37.50 and 36 ppm in that order, were moderately active.

  17. Cytotoxicity study of pyrazole derivatives

    Directory of Open Access Journals (Sweden)

    Nusrat Binta Ahasan and Md. Rabiul Islam

    2007-12-01

    Full Text Available Pyrazolone heterocyclic compound, 3-methyl-1-phenyl-2-pyrazoline-5-one 2(a was synthesized by condensation reaction between ethyl acetoacetate and phenyl hydrazine and was converted into their corresponding heterocyclic derivatives 2(b to 2(f2. Their cytotoxicity effects were measured by brine shrimp lethality bioassay. Among them the compounds 2(b, 2(f1, and 2(f2 were highly active according to IC50 values 19.50, 19.50 and 20 ppm respectively. The rest of compounds 2(a, 2(c, 2(d1, and 2(d2 having IC50 values 38, 33.50, 37.50, 36, 37.50 and 36 ppm in that order, were moderately active.

  18. Superconducting proton ring for PETRA

    International Nuclear Information System (INIS)

    Baynham, E.

    1979-01-01

    A powerful new facility for colliding beam physics could be provided by adding a proton storage ring in the range of several hundred GeV to the electron-positron storage ring PETRA at DESY. This can be achieved in an economic way utilizing the PETRA tunnel and taking advantage of the higher magnetic fields of superconducting magnets which would be placed above or below the PETRA magnets. A central field of 4 Tesla in the bending magnets corresponds to a proton energy of 225 GeV. (orig.)

  19. INVITED TALK: Dynamics Of Planetary Rings

    Science.gov (United States)

    Tiscareno, Matthew S.

    2011-04-01

    Planetary rings are the only nearby astrophysical disks, and the only disks that have been investigated by spacecraft (especially the Cassini spacecraft orbiting Saturn). Although there are significant differences between rings and other disks, chiefly the large planet/ring mass ratio that greatly enhances the flatness of rings (aspect ratios as small as 1e-7), understanding of disks in general can be enhanced by understanding the dynamical processes observed at close-range and in real-time in planetary rings. We will review the known ring systems of the four giant planets, as well as the prospects for ring systems yet to be discovered. We will then review planetary rings by type. The A, B, and C rings of Saturn, plus the Cassini Division, comprise our solar system's only dense broad disk and host many phenomena of general application to disks including spiral waves, gap formation, self-gravity wakes, viscous overstability and normal modes, impact clouds, and orbital evolution of embedded moons. Dense narrow rings are found both at Uranus (where they comprise the main rings entirely) and at Saturn (where they are embedded in the broad disk), and are the primary natural laboratory for understanding shepherding and self-stability. Narrow dusty rings, likely generated by embedded source bodies, are surprisingly found to sport azimuthally-confined arcs both at Saturn, Jupiter, and Neptune. Finally, every known ring system includes a substantial component of diffuse dusty rings.

  20. Soft Neutrosophic Ring and Soft Neutrosophic Field

    Directory of Open Access Journals (Sweden)

    Mumtaz Ali

    2014-04-01

    Full Text Available In this paper we extend the theory of neutrosophic rings and neutrosophic fields to soft sets and construct soft neutrosophic rings and soft neutrosophic fields. We also extend neutrosophic ideal theory to form soft neutrosophic ideal over a neutrosophic ring and soft neutrosophic ideal of a soft neutrosophic ring. We have given many examples to illustrate the theory of soft neutrosophic rings and soft neutrosophic fields and display many properties of these. At the end of this paper we gave soft neutrosophic ring homomorphism.

  1. Thomson's Jumping Ring Over a Long Coil

    Science.gov (United States)

    Jeffery, Rondo N.; Amiri, Farhang

    2018-03-01

    The classic jumping ring apparatus consists of a coil with an iron core that extends out of the coil. A copper or aluminum ring placed over the iron core jumps upward when AC power is applied to the coil. In this paper we will examine a modified design of the jumping ring apparatus, called the "long-coil design." It allows the ring to jump upward or downward, depending on the starting position of the ring. These features shed significant light on the study of the force that causes the ring to jump.

  2. E-læring

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2001-01-01

    E-læring er et modeord og et mantra. Undervisning bliver ikke automatisk bedre af, at der sættes et ”e-” foran. Forbedring og fornyelse af undervisningen er betinget af, at vi forstår computermediets muligheder og skaber forandring ved at tilpasse det til de undervisningsformer, vi ønsker....

  3. ring og it

    DEFF Research Database (Denmark)

      Antologien er et bidrag til didaktiske diskussioner om brug af f.eks. programpakker til sprogundervisning, præsentationsprogrammel og konferencesystemer på de videregående uddannelser. Antologien diskuterer ideen om, at multimediale medier og internettet kan understøtte læring, undervisning og ...

  4. Ring laser frequency biasing mechanism

    International Nuclear Information System (INIS)

    McClure, R.E.

    1975-01-01

    A ring laser cavity including a magnetically saturable member for differentially phase shifting the contradirectional waves propagating in the laser cavity, the phase shift being produced by the magneto-optic interaction occurring between the light waves and the magnetization in the cavity forming component as the light waves are reflected therefrom is described

  5. Counting problems for number rings

    NARCIS (Netherlands)

    Brakenhoff, Johannes Franciscus

    2009-01-01

    In this thesis we look at three counting problems connected to orders in number fields. First we study the probability that for a random polynomial f in Z[X] the ring Z[X]/f is the maximal order in Q[X]/f. Connected to this is the probability that a random polynomial has a squarefree

  6. Wands of the Black Ring

    Czech Academy of Sciences Publication Activity Database

    Pravda, Vojtěch; Pravdová, Alena

    2005-01-01

    Roč. 37, č. 7 (2005), s. 1277-1287 ISSN 0001-7701 R&D Projects: GA ČR GP202/03/P017; GA AV ČR KJB1019403 Institutional research plan: CEZ:AV0Z10190503 Keywords : algebraic classification * Petrov classification * black ring Subject RIV: BA - General Mathematics Impact factor: 1.550, year: 2005

  7. On commutativity theorems for rings

    Directory of Open Access Journals (Sweden)

    H. A. S. Abujabal

    1990-01-01

    Full Text Available Let R be an associative ring with unity. It is proved that if R satisfies the polynomial identity [xny−ymxn,x]=0(m>1,n≥1, then R is commutative. Two or more related results are also obtained.

  8. Cytotoxic Effects of Bangladeshi Medicinal Plant Extracts

    Directory of Open Access Journals (Sweden)

    Shaikh J. Uddin

    2011-01-01

    Full Text Available To investigate the cytotoxic effect of some Bangladeshi medicinal plant extracts, 16 Bangladeshi medicinal plants were successively extracted with n-hexane, dichloromethane, methanol and water. The methanolic and aqueous extracts were screened for cytotoxic activity against healthy mouse fibroblasts (NIH3T3 and three human cancer-cell lines (gastric: AGS; colon: HT-29; and breast: MDA-MB-435S using the MTT assay. Two methanolic extracts (Hygrophila auriculata and Hibiscus tiliaceous and one aqueous extract (Limnophila indica showed no toxicity against healthy mouse fibroblasts, but selective cytotoxicity against breast cancer cells (IC50 1.1–1.6 mg mL−1. Seven methanolic extracts from L. indica, Clerodendron inerme, Cynometra ramiflora, Xylocarpus moluccensis, Argemone mexicana, Ammannia baccifera and Acrostichum aureum and four aqueous extracts from Hygrophila auriculata, Bruguiera gymnorrhiza, X. moluccensis and Aegiceras corniculatum showed low toxicity (IC50 > 2.5 mg mL−1 against mouse fibroblasts but selective cytotoxicity (IC50 0.2–2.3 mg mL−1 against different cancer cell lines. The methanolic extract of Blumea lacera showed the highest cytotoxicity (IC50 0.01–0.08 mg mL−1 against all tested cell lines among all extracts tested in this study. For some of the plants their traditional use as anticancer treatments correlates with the cytotoxic results, whereas for others so far unknown cytotoxic activities were identified.

  9. Cytotoxic chalcones from some Indonesian Cryptocarya

    Science.gov (United States)

    Kurniadewi, F.; Syah, Y. M.; Juliawaty, L. D.; Hakim, E. H.; Koyama, K.; Kinoshita, K.

    2017-07-01

    Malignant tumors are one of the main causes of death in the world. Until now the search for cytotoxic (antitumor) compounds from nature, particularly from plants, is being a continuation activities. One group of plants that produce potential cytotoxic compounds is the Cryptocarya, one of the large genera of the Lauraceae family. As a part of our chemical and cytotoxic evaluation of the Cryptocarya species, we examined three species of Indonesian Cryptocarya. The sample of the wood of C. konishii hayata was collected from Cibodas Botanical Garden, West Java while the stem bark of C. phoebeopsis and C. cagayanensis were obtained from Sorong, Papua. Our investigation of flavonoid constituents on these species afforded three chalcone compounds i.e. desmethylinfectocaryone (1), infectocaryone (2) and cryptocaryone (3). The molecular structures of the isolated compounds were determined based on spectroscopic data, including UV, IR, 1D and 2D NMR. Cytotoxic effects of the compounds were evaluated using MTT [3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay. Compound 1, 2 and 3 displayed strong cytotoxic properties (IC50 cells whereas 2 and 3 exhibited strong cytotoxicity properties against HCT116 (colon cancer). Cryptocaryone (3) also showed moderate cytotoxic properties (IC50 cells.

  10. Revealing the Cytotoxicity of Residues of Phosphazene Catalysts Used for Synthesis of Poly(ethylene oxide)

    KAUST Repository

    Xia, Yening

    2017-08-24

    We herein report a case study on the toxicity of residual catalyst in metal-free polymer. Eight-arm star-like poly(ethylene oxide)s were successfully synthesized via phosphazene-catalyzed ring-opening polymerization of ethylene oxide using sucrose as an octahydroxy initiator. The products were subjected to MTT assay using human cancer cell lines (MDA-MB-231 and A2780). Comparison between the crude and purified products clearly revealed that the residual phosphazenium salts were considerably cytotoxic regardless of the anionic species, and that the cytotoxicity of more bulky t-BuP4 salt was higher than that of t-BuP2 salt. Such results have therefore put forward the necessity for removal of the catalyst residues from PEO-based polymers synthesized through phosphazene catalysis for bio-related applications, and for the development of less or non-toxic organocatalysts for such polymers.

  11. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

    Science.gov (United States)

    Ktsoyan, Zhanna A.; Beloborodova, Natalia V.; Sedrakyan, Anahit M.; Osipov, George A.; Khachatryan, Zaruhi A.; Manukyan, Gayane P.; Arakelova, Karine A.; Hovhannisyan, Alvard I.; Arakelyan, Arsen A.; Ghazaryan, Karine A.; Zakaryan, Magdalina K.; Aminov, Rustam I.

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome. PMID:23373011

  12. The Investigation of the Interaction between Human Serum Transferring with Colchicine in the Presence of Pb+2 Ions: Synchronous Fluorescence Measurements

    Directory of Open Access Journals (Sweden)

    Goldouzian Z. Goldouzian F., Momen-Heravi M. and Chamani J.

    2012-01-01

    Full Text Available The interaction between Holo-Transferin (HTF and Colchicine (COL was investigated in the present of Pb+2 ions under physiological conditions by using synchronous fluorescence spectra. The synchronous fluorescence spectra show a slight change of tryptophan residue micro-environment. Synchronous fluorescence spectra show that the structure of the tyrosine residue environment was altered by interaction of the COL and Pb+2 ions with HTF. The fluorescence intensity of HTF decreased regularly beside a small blue shift with increasing concentrations of COL and Pb+2 ions. The intrinsic fluorescence of HTF was quenched in the presence of drug and ion. Interaction of drugs with HTF and HTF-Pb+2 can elucidate the properties of drug-protein and ion- protein complex, as it may provide useful information about the structural feature that determines the therapeutic effectiveness of ion and drugs. Therefore, it has become a significant research field in life science, chemistry, biotechnology and clinical medicine.

  13. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

    Directory of Open Access Journals (Sweden)

    Zhanna eKtsoyan

    2013-01-01

    Full Text Available In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever, the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  14. International Tree Ring Data Bank (ITRDB)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tree ring data from the International Tree Ring Data Bank and World Data Center for Paleoclimatology archives. Data include raw treering measurements (most are...

  15. Planetary science: Shepherds of Saturn's ring

    Science.gov (United States)

    Crida, Aurélien

    2015-09-01

    Saturn's F ring is chaperoned on both sides by the tiny moons Prometheus and Pandora. Numerical simulations show that this celestial ballet can result from the collision of two aggregates that evolved out of Saturn's main rings.

  16. Planetary ring systems properties, structures, and evolution

    CERN Document Server

    Murray, Carl D

    2018-01-01

    Planetary rings are among the most intriguing structures of our solar system and have fascinated generations of astronomers. Collating emerging knowledge in the field, this volume reviews our current understanding of ring systems with reference to the rings of Saturn, Uranus, Neptune, and more. Written by leading experts, the history of ring research and the basics of ring–particle orbits is followed by a review of the known planetary ring systems. All aspects of ring system science are described in detail, including specific dynamical processes, types of structures, thermal properties and their origins, and investigations using computer simulations and laboratory experiments. The concluding chapters discuss the prospects of future missions to planetary rings, the ways in which ring science informs and is informed by the study of other astrophysical disks, and a perspective on the field's future. Researchers of all levels will benefit from this thorough and engaging presentation.

  17. Design, synthesis and structure-activity relationships studies on the D ring of the natural product triptolide.

    Science.gov (United States)

    Xu, Hongtao; Tang, Huanyu; Feng, Huijin; Li, Yuanchao

    2014-02-01

    Triptolide is a diterpene triepoxide natural product isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal herb. Triptolide has previously been shown to possess antitumor, anti-inflammatory, immunosuppressive, and antifertility activities. Earlier reports suggested that the five-membered unsaturated lactone ring (D ring) is essential for potent cytotoxicity, however, to the best of our knowledge, systematic structure-activity relationship studies have not yet been reported. Here, four types of D ring-modified triptolide analogues were designed, synthesized and evaluated against human ovarian (SKOV-3) and prostate (PC-3) carcinoma cell lines. The results suggest that the D ring is essential to potency, however it can be modified, for example to C18 hydrogen bond acceptor and/or donor furan ring analogues, without complete loss of cytotoxic activity. Interestingly, evaluation of the key series of C19 analogues showed that this site is exquisitely sensitive to polarity. Together, these results will guide further optimization of this natural product lead compound for the development of potent and potentially clinically useful triptolide analogues. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Nonlinear analysis of ring oscillator circuits

    KAUST Repository

    Ge, Xiaoqing

    2010-06-01

    Using nonlinear systems techniques, we analyze the stability properties and synchronization conditions for ring oscillator circuits, which are essential building blocks in digital systems. By making use of its cyclic structure, we investigate local and global stability properties of an n-stage ring oscillator. We present a sufficient condition for global asymptotic stability of the origin and obtain necessity if the ring oscillator consists of identical inverter elements. We then give a synchronization condition for identical interconnected ring oscillators.

  19. On P-coherent endomorphism rings

    Indian Academy of Sciences (India)

    A ring is called right -coherent if every principal right ideal is finitely presented. Let M R be a right -module. We study the -coherence of the endomorphism ring of M R . It is shown that is a right -coherent ring if and only if every endomorphism of M R has a pseudokernel in add M R ; S is a left -coherent ring if and ...

  20. Tree-ring anomalies in Toona ciliata

    OpenAIRE

    Heinrich, Ingo; Banks, John Charles Gripper

    2006-01-01

    New increment core samples of Toona ciliata collected in the Australian tropics and subtropics compared to already existing material from the Upper Kangaroo Valley, near Sydney exhibit distinct differences in tree-ring structures. This necessitated a closer examination of the wood anatomy, possible false rings and the species’ crossdating capacity in northeast Australia. During tree-ring analysis two growth anomalies (extensive zones of narrow and indistinct rings) and three types of false ri...

  1. The Hi-Ring DCN Architecture

    DEFF Research Database (Denmark)

    Galili, Michael; Kamchevska, Valerija; Ding, Yunhong

    2016-01-01

    We will review recent work on the proposed hierarchical ring-based architecture (HiRing) proposed for data center networks. We will discuss the architecture and initial demonstrations of optical switching performance and time-domain synchronization......We will review recent work on the proposed hierarchical ring-based architecture (HiRing) proposed for data center networks. We will discuss the architecture and initial demonstrations of optical switching performance and time-domain synchronization...

  2. Random Implantation of Asymmetric Intracorneal Rings

    Directory of Open Access Journals (Sweden)

    Cristina Peris-Martínez

    2014-01-01

    Full Text Available Intracorneal ring employment for treating ectasia is widespread. Although the mechanism of action of intracorneal rings in the regularization of the corneal surface after its implantation is well known in most cases, there are still many doubts. We present a case of implanted intracorneal rings, where, despite the peculiar position of the rings, the patient gains lines of visual acuity and keratoconus remains stable.

  3. Edge-on View of Saturn's Rings

    Science.gov (United States)

    1996-01-01

    TOP - This is a NASA Hubble Space Telescope snapshot of Saturn with its rings barely visible. Normally, astronomers see Saturn with its rings tilted. Earth was almost in the plane of Saturn's rings, thus the rings appear edge-on.In this view, Saturn's largest moon, Titan, is casting a shadow on Saturn. Titan's atmosphere is a dark brown haze. The other moons appear white because of their bright, icy surfaces. Four moons - from left to right, Mimas, Tethys, Janus, and Enceladus - are clustered around the edge of Saturn's rings on the right. Two other moons appear in front of the ring plane. Prometheus is on the right edge; Pandora, on the left. The rings also are casting a shadow on Saturn because the Sun was above the ring plane.BOTTOM - This photograph shows Saturn with its rings slightly tilted. The moon called Dione, on the lower right, is casting a long, thin shadow across the whole ring system due to the setting Sun on the ring plane. The moon on the upper left of Saturn is Tethys.Astronomers also are studying the unusual appearance of Saturn's rings. The bottom image displays a faint, narrow ring, the F-ring just outside the main ring, which normally is invisible from Earth. Close to the edge of Saturn's disk, the front section of rings seem brighter and more yellow than the back due to the additional lumination by yellowish Saturn.The color images were assembled from separate exposures taken August 6 (top) and November 17 (bottom), 1995 with the Wide Field Planetary Camera-2.The Wide Field/Planetary Camera 2 was developed by the Jet Propulsion Laboratory and managed by the Goddard Spaced Flight Center for NASA's Office of Space Science.This image and other images and data received from the Hubble Space Telescope are posted on the World Wide Web on the Space Telescope Science Institute home page at URL http://oposite.stsci.edu/pubinfo/

  4. Optical fiber having wave-guiding rings

    Science.gov (United States)

    Messerly, Michael J [Danville, CA; Dawson, Jay W [Livermore, CA; Beach, Raymond J [Livermore, CA; Barty, Christopher P. J. [Hayward, CA

    2011-03-15

    A waveguide includes a cladding region that has a refractive index that is substantially uniform and surrounds a wave-guiding region that has an average index that is close to the index of the cladding. The wave-guiding region also contains a thin ring or series of rings that have an index or indices that differ significantly from the index of the cladding. The ring or rings enable the structure to guide light.

  5. Genotoxicity and cytotoxicity of oxindole alkaloids from Uncaria tomentosa (cat's claw): Chemotype relevance.

    Science.gov (United States)

    Kaiser, Samuel; Carvalho, Ânderson Ramos; Pittol, Vanessa; Dietrich, Fabrícia; Manica, Fabiana; Machado, Michel Mansur; de Oliveira, Luis Flávio Souza; Oliveira Battastini, Ana Maria; Ortega, George González

    2016-08-02

    Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) or cat's claw is a climber vine from the South American rainforest used in folk medicine for cancer treatment. Its antitumor activity has been mostly ascribed to pentacyclic oxindole alkaloids (POA) from stem bark and leaves while the activity of tetracyclic oxindole alkaloids (TOA) remains unknown. In recent times, the occurrence of three chemotypes based on its oxindole alkaloid profile was noticed in U. tomentosa, namely, chemotype I (POA cis D/E ring junction); chemotype II (POA trans D/E ring junction) or chemotype III (TOA). Consequently, the relationship between the chemotype and cytotoxic and genotoxic activities deserves attention. To evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models. Four authentic stem bark cat's claw samples (SI-SIV) and two leaf samples (LII and LIII) were analyzed by HPLC-PDA, properly extracted and fractioned by ion-exchange to obtain oxindole alkaloid purified fractions (OAPFs). The freeze-dried fractions were assayed for genotoxicity and cytotoxicity against human leukocytes (non malignant cell line) by the micronuclei frequency method and the alkaline comet DNA assay, and the trypan blue method, respectively. Moreover, the cytotoxicity of each OAPF was evaluated against a human bladder cancer cell line (T24) and human glioblastoma cell line (U-251-MG) by MTT method (malignant cell lines). Additionally, the isomerization of oxindole alkaloids throughout the course of cell incubation was monitored by HPLC-PDA. Based on HPLC-PDA analyses, sample SI was characterized as chemotype I, while samples SII and LII were characterized as chemotype II, and samples SIII, SIV and LIII as chemotype III. The chemotypes showed comparable cytotoxic activity toward malignant cell lines (T24 and U-251-MG) unlike human leukocytes (non malignant cell line), where this activity was clearly distinct

  6. Minor valepotriates from Valeriana jatamansi and their cytotoxicity against metastatic prostate cancer cells.

    Science.gov (United States)

    Lin, Sheng; Fu, Peng; Chen, Tao; Ye, Ji; Su, Yong-Qing; Yang, Xian-Wen; Zhang, Zhong-Xiao; Zhang, Wei-Dong

    2015-01-01

    Ten new valepotriates, jatamanvaltrates P-Y (1-10) and a known one, nardostachin (11), have been isolated from the whole plants of Valeriana jatamansi. The structures of the new compounds were determined by detailed spectroscopic data analysis. The isolated compounds were evaluated for cytotoxic activity against PC-3M cells, and a structure-activity relationship was examined for all the valepotriates isolated from V. jatamansi. The results highlighted the structure-activity relationship importance of the C-3-C-4 double bond, the oxirane ring, and the 10-chlorine in the valepotriates. Georg Thieme Verlag KG Stuttgart · New York.

  7. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...... and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed....

  8. Self-gravitation in Saturn's rings

    International Nuclear Information System (INIS)

    Salo, H.; Lukkari, J.

    1982-01-01

    In a ring-shaped collisional system self-gravitation reduces the equilibrium values of the geometric and optical thickness. In Saturn's rings both effects are appreciable. The previously found discrepancy between the calculated profile and the observed profile of the rings is chiefly caused by the omission of self-gravitation. (Auth.)

  9. Anomalous dark growth rings in black cherry

    Science.gov (United States)

    Robert P. Long; David W. Trimpey; Michael C. Wiemann; Susan L. Stout

    2012-01-01

    Anomalous dark growth rings have been observed in black cherry (Prunus serotina) sawlogs from northwestern Pennsylvania making the logs unsuitable for veneer products. Thirty-six cross sections with dark rings, each traceable to one of ten stands, were obtained from a local mill and sections were dated and annual ring widths were measured. One or...

  10. A Ring Construction Using Finite Directed Graphs

    Science.gov (United States)

    Bardzell, Michael

    2012-01-01

    In this paper we discuss an interesting class of noncommutative rings which can be constructed using finite directed graphs. This construction also creates a vector space. These structures provide undergraduate students connections between ring theory and graph theory and, among other things, allow them to see a ring unity element that looks quite…

  11. Molecular cytotoxic mechanisms of anticancer hydroxychalcones.

    Science.gov (United States)

    Sabzevari, Omid; Galati, Giuseppe; Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

    2004-06-30

    Chalcones are being considered as anticancer agents as they are natural compounds that are particularly cytotoxic towards K562 leukemia or melanoma cells. In this study, we have investigated phloretin, isoliquiritigenin, and 10 other hydroxylated chalcones for their cytotoxic mechanisms towards isolated rat hepatocytes. All hydroxychalcones partly depleted hepatocyte GSH and oxidized GSH to GSSG. These chalcones also caused a collapse of mitochondrial membrane potential and increased oxygen uptake. Furthermore, glycolytic or citric acid cycle substrates prevented cytotoxicity and mitochondrial membrane potential collapse. The highest pKa chalcones were the most effective at collapsing the mitochondrial membrane potential which suggests that the cytotoxic activity of hydroxychalcones are likely because of their ability to uncouple mitochondria.

  12. Laser driven structured quantum rings

    Science.gov (United States)

    Castiglia, Giuseppe; Corso, Pietro Paolo; De Giovannini, Umberto; Fiordilino, Emilio; Frusteri, Biagio

    2015-06-01

    In this work we study harmonic emission from structured quantum rings (SQRs). In SQRs, electrons trapped in two-dimensional structures are further confined by an external potential composed of N scattering centers arranged on a circle. We build a suitable one-dimensional model Hamiltonian describing this class of systems and analytically solve the associated Schödinger equation. We find that the solution can be expressed in terms of Mathieu functions and focus on the specific case of N = 6. By exactly solving the time-dependent Schödinger equation, we then show how the harmonic response to linearly polarized lasers strongly depends on the ring physical parameters. The results illustrate how the additional degrees of freedom introduced by these parameters provide important handles to control the emitted spectrum that in some cases extends into the XUV region.

  13. Fiber Ring Optical Gyroscope (FROG)

    Science.gov (United States)

    1979-01-01

    The design, construction, and testing of a one meter diameter fiber ring optical gyro, using 1.57 kilometers of single mode fiber, are described. The various noise components: electronic, thermal, mechanical, and optical, were evaluated. Both dc and ac methods were used. An attempt was made to measure the Earth rotation rate; however, the results were questionable because of the optical and electronic noise present. It was concluded that fiber ring optical gyroscopes using all discrete components have many serious problems that can only be overcome by discarding the discrete approach and adapting an all integrated optic technique that has the laser source, modulator, detector, beamsplitters, and bias element on a single chip.

  14. Behavioral Mapless Navigation Using Rings

    Science.gov (United States)

    Monroe, Randall P.; Miller, Samuel A.; Bradley, Arthur T.

    2012-01-01

    This paper presents work on the development and implementation of a novel approach to robotic navigation. In this system, map-building and localization for obstacle avoidance are discarded in favor of moment-by-moment behavioral processing of the sonar sensor data. To accomplish this, we developed a network of behaviors that communicate through the passing of rings, data structures that are similar in form to the sonar data itself and express the decisions of each behavior. Through the use of these rings, behaviors can moderate each other, conflicting impulses can be mediated, and designers can easily connect modules to create complex emergent navigational techniques. We discuss the development of a number of these modules and their successful use as a navigation system in the Trinity omnidirectional robot.

  15. Livslang læring

    DEFF Research Database (Denmark)

    Larson, Anne

    2016-01-01

    Pædagogisk sociologi beskæftiger sig blandt andet med de politiske rammebetingelser for opdragelse, undervisning, socialisering og uddannelse. I dette kapitel præsenteres en komparativ undersøgelse af EU’s politik med hensyn til livslang læring på den ene side, og den danske politik og lovgivning...... tilgang kaldet ‘What is the problem represented to be?’...

  16. ring og vejledning

    DEFF Research Database (Denmark)

    Ambjørn, Lone

    Formålet med kompendiet om forskellige aspekter omkring sproglig læring er at ruste de studerende til studiet på en højere læreranstalt; at højne effektiviteten i deres sproglige læringsproces; at lære de studerende at arbejde uafhængigt af underviseren; at give de studerende de nødvendige redska...

  17. Two superconducting storage rings: ISABELLE

    International Nuclear Information System (INIS)

    Sanford, J.R.

    1978-01-01

    The general features of the design and the status of the ISABELLE storage ring project at the present time are reported. It brings up to date the results reported at the National Particle Accelerator Conference in March 1977. The most significant change since that time has been an upgrading of the energy of the overall facility, and acceptance of the project by the Department of Energy

  18. ring mellem elever

    DEFF Research Database (Denmark)

    Georgsen, Marianne; Davidsen, Jacob

    2010-01-01

    I denne rapport præsenteres resultater fra følgeforskningen til projektet Læring gennem Bevægelse, som er gennemført på Søndervangskolen i Hammel i perioden august 2009 - maj 2010. Projektet er gennemført i samspil mellem lærere, it-vejleder, elever og skolens ledelse. Projektets overordnede formål...

  19. ring mellem elever

    DEFF Research Database (Denmark)

    Davidsen, Jacob; Georgsen, Marianne

    I denne rapport tilbyder vi et indblik i det gennemførte projekt, og forfatterne har valgt nogle forhold ud, som belyses og diskuteres, mens andre ikke berøres eller diskuteres nævneværdigt i denne rapport. Det skyldes blandt andet projektets mange facetter, som dækker både læring, teknologi, pæd...

  20. Progressiv læring

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne

    2017-01-01

    undervisningen. • At der afsættes tid til implementeringen, og at det gøres tydeligt, at implementering tager tid. • At organiseringen af undervisningen på skolerne tilpasses, så det letter anvendelsen af principperne i Progressiv Læring. • At lærernes kompetenceudvikling er forankret på skolen både emnemæssigt...

  1. Oxidative Mechanisms of Monocyte-Mediated Cytotoxicity

    Science.gov (United States)

    Weiss, Stephen J.; Lobuglio, Albert F.; Kessler, Howard B.

    1980-01-01

    Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism.

  2. Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

    Directory of Open Access Journals (Sweden)

    Emmy Tuenter

    2017-02-01

    Full Text Available Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship models were developed, using PLS (partial least squares regression and MLR (multiple linear regression. On the one hand, these models allow for the indication of the most important descriptors (molecular properties responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study.

  3. Studies on some quantitative characters in the M2 generation in jute (Corchorus olitorius L.) originating after pre-irradiation treatments with hydroxylamine and pre- and post-irradiation treatments with colchicine

    International Nuclear Information System (INIS)

    Bose, S.; Chakrabarti, C.C.; Banerjee, B.

    1977-01-01

    Studies on quantitative characters have been made on M 2 mutants like - slender plants with many branches and oval shaped leaves, plants with bifurcation at the base of the stem, stout dwarf plants with many branches, slender plants with many branches, small, slender plants with lesser number of branches, slender, tall plants with many branches, tall plants with crincked leaves and many branches and in the bulk type having many branches and tall habit. The bulk types originated after pre-irradiation treatment with hydroxylamine, colchicine and post-irradiation treatment with colchicine and the mutants originated after pre-irradiation treatment with hydroxylamine and distilled water. The quantitative characters taken into consideration were plant height, basal diameter, number of nodes per plant, number pods per plant, number of seeds per pod and 100 seed weight. (author)

  4. The cytotoxicity study of praziquantel enantiomers.

    Science.gov (United States)

    Sun, Qian; Mao, Ruifeng; Wang, Dongling; Hu, Changyan; Zheng, Yang; Sun, Dequn

    2016-01-01

    Praziquantel (PZQ) is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ), which is composed of (R)-PZQ and (S)-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R)-PZQ and (S)-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay. Results revealed that (R)-PZQ had negligible cytotoxicity against L-02, SH-SY5Y, HUVEC, A549, HCT-15, and Raw264.7 cells but selectively inhibited tumor cell lines (prf-plc-5 and HepG2). However, in contrast to (R)-PZQ, the (S)-isomer showed higher cytotoxicity against L-02 cells and lower inhibition on prf-plc-5 and HepG2 cells. Besides, (R)-PZQ showed lower cytotoxicity on SH-SY5Y cells than (S)-PZQ. Meanwhile, (R)-PZQ at cytotoxicity than (S)-PZQ and has similar cytotoxicity with rac-PZQ. (S)-PZQ is the principal enantiomer to cause side effects on human definitive hosts. These findings gave the reasonable reasons for World Health Organization to produce (R)-PZQ as a replacement for rac-PZQ for the treatment of schistosomiasis.

  5. MOF-5(Zn)-Fe2O4 nanocomposite based magnetic solid-phase microextraction followed by HPLC-UV for efficient enrichment of colchicine in root of colchicium extracts and plasma samples.

    Science.gov (United States)

    Bahrani, Sonia; Ghaedi, Mehrorang; Dashtian, Kheibar; Ostovan, Abbas; Mansoorkhani, Mohammad Javad Khoshnood; Salehi, Amin

    2017-11-01

    In present work, facile method is developed for determination of colchicine in human plasma sample, autumn and spring root of colchicium extracts by ultrasound assisted dispersive magnetic solid phase microextraction followed by HPLC-UV method (UAD-MSPME-HPLC-UV). Magnetic (Fe 2 O 4 -nanoparticles) metal organic framework-5, (MOF-5(Zn)-Fe 2 O 4 NPs) was synthesized by dispersing MOF-5 and Fe(NO 3 ) 3 .9H 2 O in ethylene glycol (as capping agent) and NaOH (pH adjustment agent) by hydrothermal method. The prepared sorbent was characterized via XRD and SEM analysis and applied as magnetic solid phase in UAD-MSPME-HPLC-UV method. In this method, colchicine molecules were sorbed on MOF-5(Zn)-Fe 2 O 4 NPs sorbent by various mechanisms like ion exchange, hydrogen bonding and electrostatic, ᴨ-ᴨ, hard-hard and dipole-ion interaction followed by exposing sonication waves as incremental mass transfer agent and then the sorbent was separated from the sample matrix by an external magnetic fields. Subsequently, accumulated colchicine were eluted by small volume of desorption organic solvent. Influence of operational variables such as MOF-5(Zn)-Fe 2 O 4 NPs mass, volume of extracting solvent and sonication time on response property (recovery) were studied and optimized by central composite design (CCD) combined with desirability function (DF) approach. Under optimum condition, the method has wide linear calibration rang (0.5-1700ngmL -1 ) with reasonable detection limit (0.13ngmL -1 ) and R 2 =0.9971. Finally, the UAD-MSPME-HPLC-UV method was successfully applied for determination of colchicine autumn and spring root of colchicium extracts and plasma samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Multi-wavelength studies of Saturn's rings to constrain ring particle properties and ring structure

    Science.gov (United States)

    Spilker, L.; Deau, E.; Morishima, R.; Filacchione, G.; Hedman, M.; Nicholson, P.; Colwell, J.; Bradley, T.

    2012-04-01

    A great deal can be learned about the nature of Saturn's ring particles and their regoliths by modeling the changes in brightness, color and temperature with changing viewing geometry over a wide range of wavelengths, from ultraviolet through the thermal infrared. Data from Cassini's Composite Infrared Spectrometer (CIRS), Visual and Infrared Mapping Spectrometer (VIMS), Imaging Science Subsystem (ISS) and Ultraviolet Imaging Spectrograph (UVIS) are jointly being studied using scans of the lit and unlit main rings (A, B, C and Cassini Division) at multiple geometries and solar elevations. Using multi-wavelength data sets allow us to test different thermal models by combining the effects of particle albedo, regolith grain size and surface roughness with thermal emissivity and inertia, particle spin rate and spin axis orientation. With the high spatial resolution of the Cassini data it is now possible to analyze these effects at smaller spatial scales and characterize regions such as the C ring plateaus and ringlets, where albedo differences may be present. In the CIRS data, over a range of solar elevations from -23 degrees to -8 degrees, the bulk of the temperature variations are confined primarily to phase angle. Only small temperature differences are observed with changing spacecraft elevation. Similar behavior is seen in the ISS color data. Color and temperature dependence with changing solar elevation angle are also observed. VIMS observations show that the IR ice absorption band depths are (almost) independent of phase angle, out to ~140 deg phase, suggesting that interparticle light scattering is relatively unimportant except at very high phase angles. These results imply that the individual properties of the ring particles may play a larger role than the collective properties of the rings, in particular at visible wavelengths. The temperature and color variation with phase angle may be a result of scattering within the regolith and on possibly rough surfaces

  7. Polyurethane Foams with Pyrimidine Rings

    Directory of Open Access Journals (Sweden)

    Kania Ewelina

    2014-09-01

    Full Text Available Oligoetherols based on pyrimidine ring were obtained upon reaction of barbituric acid with glycidol and alkylene carbonates. These oligoetherols were then used to obtain polyurethane foams in the reaction of oligoetherols with isocyanates and water. The protocol of foam synthesis was optimized by the choice of proper kind of oligoetherol and synthetic composition. The thermal resistance was studied by dynamic and static methods with concomitant monitoring of compressive strength. The polyurethane foams have similar physical properties as the classic ones except their enhanced thermal resistance. They stand long-time heating even at 200°C. Moreover thermal exposition of foams results generally in increase of their compressive strength.

  8. Ring with changeable radiation dosimeter

    International Nuclear Information System (INIS)

    Collica, C.; Epifano, L.; Farella, R.

    1976-01-01

    A ring for housing a disc of radiation measuring material is described comprising a band having a circular shape and a housing integral with the band. The housing comprises a hollow cylindrical section substantially normal to the band surface and terminating in an inwardly disposed annular flange which defines a substantially circular aperture. In a preferred embodiment of the invention a retaining protrusion formed on the inside of the cylindrical section and spaced from the annular flange is provided to retain a plurality of discs mounted in the housing in layered fashion

  9. Storage ring proton EDM experiment

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    sensitivity of 10^-29 e-cm.  The strength of the method originates from the fact that there are high intensity polarized proton beams available and the fact that the so-called geometric phase systematic error background cancels with clock-wise and counter-clock-wise storage possible in electric rings. The ultimate sensitivity of the method is 10^-30 e-cm. At this level it will either detect a non-zero EDM or it will eliminate electro-weak baryogenesis.

  10. Longitudinal dynamics in storage rings

    International Nuclear Information System (INIS)

    Colton, E.P.

    1986-01-01

    The single-particle equations of motion are derived for charged particles in a storage ring. Longitudinal space charge is included in the potential assuming an infinitely conducting circular beam pipe with a distributed inductance. The framework uses Hamilton's equations with the canonical variables phi and W. The Twiss parameters for longitudinal motion are also defined for the small amplitude synchrotron oscillations. The space-charge Hamiltonian is calculated for both parabolic bunches and ''matched'' bunches. A brief analysis including second-harmonic rf contributions is also given. The final sections supply calculations of dynamical quantities and particle simulations with the space-charge effects neglected

  11. Interface-læring

    DEFF Research Database (Denmark)

    Thorhauge, Sally

    2015-01-01

    Interface-læring er den læringsoplevelse, der kan opstå i grænsefladen mellem to væsensforskellige læringsmiljøer, når de mødes og griber ind i hinanden. Et gymnasium og et museum er eksempler på to sådanne læringsmiljøer. Artiklen præsenterer nogle af de væsentligste resultater fra min ph.d. afh...

  12. Cytotoxicity and intracellular dissolution of nickel nanowires

    KAUST Repository

    Perez, Jose E.

    2015-12-22

    The assessment of cytotoxicity of nanostructures is a fundamental step for their development as biomedical tools. As widely used nanostructures, nickel nanowires (Ni NWs) seem promising candidates for such applications. In this work, Ni NWs were synthesized and then characterized using vibrating sample magnetometry, energy dispersive X-Ray analysis and electron microscopy. After exposure to the NWs, cytotoxicity was evaluated in terms of cell viability, cell membrane damage and induced apoptosis/necrosis on the model human cell line HCT 116. The influence of NW to cell ratio (10:1 to 1000:1) and exposure times up to 72 hours was analyzed for Ni NWs of 5.4 µm in length, as well as for Ni ions. The results show that cytotoxicity markedly increases past 24 hours of incubation. Cellular uptake of NWs takes place through the phagocytosis pathway, with a fraction of the dose of NWs dissolved inside the cells. Cell death results from a combination of apoptosis and necrosis, where the latter is the outcome of the secondary necrosis pathway. The cytotoxicity of Ni ions and Ni NWs dissolution studies suggest a synergistic toxicity between NW aspect ratio and dissolved Ni, with the cytotoxic effects markedly increasing after 24 hours of incubation.

  13. Safe handling of cytotoxics: guideline recommendations.

    Science.gov (United States)

    Easty, A C; Coakley, N; Cheng, R; Cividino, M; Savage, P; Tozer, R; White, R E

    2015-02-01

    This evidence-based practice guideline was developed to update and address new issues in the handling of cytotoxics, including the use of oral cytotoxics; the selection and use of personal protective equipment; and treatment in diverse settings, including the home setting. The guideline was developed primarily from an adaptation and endorsement of an existing guideline and from three systematic reviews. Before publication, the guideline underwent a series of peer and external reviews to gather feedback. All comments were addressed, and the guideline was amended when required. The guideline applies to health care workers who could come into contact with cytotoxic drugs at any point in the medication circuit. The intended users are hospital administrators, educators, and managers; occupational health and safety services; and pharmacy and health care workers. The recommendations represent a reasonable and practical set of procedures that the intended users of this guideline should implement to minimize opportunities for accidental exposure. They are not limited to just the point of care; they cover the entire chain of cytotoxics handling from the time such agents enter the institution until they leave in the patient or as waste. Reducing the likelihood of accidental exposure to cytotoxic agents within the medication circuit is the main objective of this evidenced-based guideline. The recommendations differ slightly from earlier guidelines because of the availability of new evidence.

  14. Boom and Bust Cycles in Saturn's Rings

    Science.gov (United States)

    Esposito, L. W.; Meinke, B. K.; Sremcevic, M.; Albers, N.

    2010-12-01

    Cassini UVIS occultation data show clumping in Saturn’s F ring and at the B ring outer edge, indicating aggregation and disaggregation at these locations perturbed by Mimas and Prometheus. Timescales range from hours to months. The maximum clumping lags the moon by roughly π in the forcing frame. This indicates a direct relation between the moon and the ring clumping. We propose that the collective behavior of the ring particles resembles a predator-prey system: the aggregate mean size is the prey, which feeds the velocity dispersion; conversely, increasing dispersion breaks up the aggregates. For realistic values of the parameters this creates a limit cycle behavior, as for the ecology of foxes and hares or the boom-bust economic cycle. Solving for the long-term behavior of this forced system gives a periodic response at the perturbing frequency, with a phase lag roughly consistent with the UVIS occultation measurements. We conclude that the agitation by the moons at both these locations in the F ring and at the B ring outer edge drives aggregation and disaggregation in the forcing frame. This agitation of the ring material allows fortuitous formation of solid objects from the temporary clumps, via stochastic processes like compaction, adhesion, sintering or reorganization that drives the denser parts of the aggregate to the center or ejects the lighter elements. These more persistent objects would then orbit at the Kepler rate. Such processes can create the equinox objects seen at the B ring edge and in the F ring, explain the ragged nature of those ring regions and allow for rare events to aggregate ring particles into solid objects, recycling the ring material and extending the ring lifetime.

  15. Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins

    Directory of Open Access Journals (Sweden)

    Alla V. Lipeeva

    2014-06-01

    Full Text Available A series of new analogs of combretastatin A-4 (CA-4, 1 with the A or B-ring replaced by a 3-oxo-2,3-dihydrofurocoumarin or a furocoumarin residue have been designed and synthesized by employing a cross-coupling approach. All the compounds were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, MT-4, U-937 using conventional MTT assays. Structure-activity relationship analysis reveals that compounds 2, 3, 6–8 in which the (Z-styryl substituent was connected to the 2-position of the 3-oxo-2,3-dihydrofurocoumarin core, demonstrated increased potency compared to 3-(Z-styrylfurocoumarins 4, 5, 9–11. The methoxy-, hydroxyl- and formyl- substitution on the aromatic ring of the (Z-styryl moiety seems to play an important role in this class of compounds. Compounds 2 and 3 showed the best potency against the CEM-13 cell lines, with CTD50 values ranging from 4.9 to 5.1 μM. In comparison with CA-4, all synthesized compounds presented moderate cytotoxic activity to the T-cellular human leucosis cells MT-4 and lymphoblastoid leukemia cells CEM-13, but most of them were active in the human monocyte cell lines U-937.

  16. The cryogenic storage ring CSR

    Science.gov (United States)

    von Hahn, R.; Becker, A.; Berg, F.; Blaum, K.; Breitenfeldt, C.; Fadil, H.; Fellenberger, F.; Froese, M.; George, S.; Göck, J.; Grieser, M.; Grussie, F.; Guerin, E. A.; Heber, O.; Herwig, P.; Karthein, J.; Krantz, C.; Kreckel, H.; Lange, M.; Laux, F.; Lohmann, S.; Menk, S.; Meyer, C.; Mishra, P. M.; Novotný, O.; O'Connor, A. P.; Orlov, D. A.; Rappaport, M. L.; Repnow, R.; Saurabh, S.; Schippers, S.; Schröter, C. D.; Schwalm, D.; Schweikhard, L.; Sieber, T.; Shornikov, A.; Spruck, K.; Sunil Kumar, S.; Ullrich, J.; Urbain, X.; Vogel, S.; Wilhelm, P.; Wolf, A.; Zajfman, D.

    2016-06-01

    An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed, and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 ± 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion), and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas density below 140 cm-3 is derived, equivalent to a room-temperature pressure below 10-14 mbar. Fast atomic, molecular, and cluster ion beams stored for long periods of time in a cryogenic environment will allow experiments on collision- and radiation-induced fragmentation processes of ions in known internal quantum states with merged and crossed photon and particle beams.

  17. Replantation of ring avulsion amputations

    Directory of Open Access Journals (Sweden)

    Sabapathy R

    2003-01-01

    Full Text Available Replantation of ring avulsion injuries is a challenge because of the long segment damage to the vessels and intrinsic damage caused to soft tissues at the proximal edge of the amputation. Eight patients with total ring avulsion amputations underwent microsurgical replantation in the period 1994 to 2002. Arterial repair was done by direct vessel suture in three patients, interposition vein grafts in two and cross anastomosis of the digital arteries in three patients. Venous anastomosis was carried out by mobilization and direct suture in seven patients and vessel transfer from the adjacent finger in one patient. Seven of the eight replantations were successful, while one patient had a partial failure. At a minimum follow-up of one year, these patients showed good functional and cosmetic recovery. All successful patients were happy with the outcome and none have requested for amputation, even those whose results were not functionally adequate. However, in addition to technical factors, it is important to evaluate the patient's motivation to undergo not only the long surgery, but also multiple secondary procedures and regular supervised physiotherapy. We also describe a simple method which prevents the soft tissues inside the degloved digit from becoming wrapped around the K wire during bony fixation, thus making one step of this technically challenging procedure a little easier.

  18. New diols with imidazoquinazoline ring

    Science.gov (United States)

    Szyszkowska, Agnieszka; Klasek, Antonin; Pawlędzio, Sylwia; Trzybiński, Damian; Woźniak, Krzysztof; Zarzyka, Iwona

    2018-02-01

    The objective of these studies was to synthesize and characterize new diols with an imidazoquinazoline ring. New diols were obtained in reactions of 2,6-bis-(ethoxycarbonylmethyl)-1-phenylimidazo[1,5-c]quinazoline-3,5-dione with excess of ethylene glycol or in reaction of 1-phenyl-2H,6H-imidazo[1,5-c]quinazoline-3,5-dione with 2-M excess of ethylene oxide. The products were isolated at high yield and characterized by instrumental methods (IR, 1H- and 13C-NMR, MS-ESI, UV, TGA). The structure of 2,6-bis(2-hydroxyethyl)-1-phenylimidazo[1,5-c]quinazoline-3,5-dione (BEFIQ) was also investigated by single-crystal X-ray diffraction. BEFIQ crystallizes in the monoclinic P21/n space group with two molecules in the asymmetric unit of the crystal lattice. The nature of the packing of molecules in the crystal lattice of BEFIQ was investigated by Hirshfeld surface analysis. The described methods enable the synthesis of new diols with an imidazoquinazoline ring. The new diols are quite soluble in typical organic solvents. Therefore, they can be used as raw materials for the synthesis of thermally stable polymers, and they can also have biological activity.

  19. A first course in noncommutative rings

    CERN Document Server

    Lam, T Y

    2001-01-01

    A First Course in Noncommutative Rings, an outgrowth of the author's lectures at the University of California at Berkeley, is intended as a textbook for a one-semester course in basic ring theory. The material covered includes the Wedderburn-Artin theory of semisimple rings, Jacobson's theory of the radical, representation theory of groups and algebras, prime and semiprime rings, local and semilocal rings, perfect and semiperfect rings, etc. By aiming the level of writing at the novice rather than the connoisseur and by stressing th the role of examples and motivation, the author has produced a text that is suitable not only for use in a graduate course, but also for self- study in the subject by interested graduate students. More than 400 exercises testing the understanding of the general theory in the text are included in this new edition.

  20. Foundations of commutative rings and their modules

    CERN Document Server

    Wang, Fanggui

    2016-01-01

    This book provides an introduction to the basics and recent developments of commutative algebra. A glance at the contents of the first five chapters shows that the topics covered are ones that usually are included in any commutative algebra text. However, the contents of this book differ significantly from most commutative algebra texts: namely, its treatment of the Dedekind–Mertens formula, the (small) finitistic dimension of a ring, Gorenstein rings, valuation overrings and the valuative dimension, and Nagata rings. Going further, Chapter 6 presents w-modules over commutative rings as they can be most commonly used by torsion theory and multiplicative ideal theory. Chapter 7 deals with multiplicative ideal theory over integral domains. Chapter 8 collects various results of the pullbacks, especially Milnor squares and D+M constructions, which are probably the most important example-generating machines. In Chapter 9, coherent rings with finite weak global dimensions are probed, and the local ring of weak gl...

  1. Report of the eRHIC Ring-Ring Working Group

    Energy Technology Data Exchange (ETDEWEB)

    Aschenauer, E. C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Berg, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blaskiewicz, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Brennan, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Fedotov, A. [Brookhaven National Lab. (BNL), Upton, NY (United States); Fischer, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Litvinenko, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Montag, C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Palmer, R. [Brookhaven National Lab. (BNL), Upton, NY (United States); Parker, B. [Brookhaven National Lab. (BNL), Upton, NY (United States); Peggs, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Ptitsyn, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Ranjbar, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Tepikian, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Trbojevic, D. [Brookhaven National Lab. (BNL), Upton, NY (United States); Willeke, F. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-10-13

    This report evaluates the ring-ring option for eRHIC as a lower risk alternative to the linac-ring option. The reduced risk goes along with a reduced initial luminosity performance. However, a luminosity upgrade path is kept open. This upgrade path consists of two branches, with the ultimate upgrade being either a ring-ring or a linac-ring scheme. The linac-ring upgrade could be almost identical to the proposed linac-ring scheme, which is based on an ERL in the RHIC tunnel. This linac-ring version has been studied in great detail over the past ten years, and its significant risks are known. On the other hand, no detailed work on an ultimate performance ring-ring scenario has been performed yet, other than the development of a consistent parameter set. Pursuing the ring-ring upgrade path introduces high risks and requires significant design work that is beyond the scope of this report.

  2. ring og den kulturhistoriske skole

    DEFF Research Database (Denmark)

    Broström, Stig

    2007-01-01

    -forskere uddrager den grundlæggende forståelse af forholdet mellem læring og udvikling. Nemlig at læring og udvikling indgår i en dialektisk enhed og virker gensidigt ind på hinanden - dog således at læring kommer ført, den trækker udviklingen med sig og så at sige leder udviklingen. Vygotskys tese vedrørende...

  3. On the potential of large ring lasers

    Science.gov (United States)

    Stedman, G. E.; Hurst, R. B.; Schreiber, K. U.

    2007-11-01

    We describe a new ring laser with area A = 833 m 2 and update performance statistics for several such machines. Chaio and Anandan [R.Y. Chaio, J. Anandan, Gen. Relat. Gravit. 14 (1982) 515-521] judged ring lasers inferior to matter interferometers as possible detectors of gravitational waves. However, we note that geophysically interesting results have been obtained from large ring lasers and that there is still a lot of room for improvements.

  4. Arkitektur krop og læring

    DEFF Research Database (Denmark)

    Gulløv, E.; Coninck-Smith, N. D.; Pedersen, S. H.

    Når vi taler om læring, tænker vi sædvanligvis på resultatet af bevidst tilrettelagt undervisningsforløb. Megen læring sker imidlertid ubevidst via den påvirkning, omgivelserne øver på vores kroppe og vores sanser. I arkitektur, krop og læring gives en teoretisk og analytisk fremstilling af forsk......, Gebauer, Wulf, Lorentzer, Merleau-Ponty, Barth, Ehn....

  5. RRF rings which are not LRF

    Indian Academy of Sciences (India)

    All the rings we consider will be associative rings with an identity element 1 TИ 0 and all the modules considered will be unital modules. In what follows A denotes a ring, mod-A. (respectively A-mod) will denote the category of right (respectively left) A-modules. Recall (Definition 2.1 in [9]) that an A-module M is said to be ...

  6. Relatively Orthocomplemented Skew Nearlattices in Rickart Rings

    Directory of Open Access Journals (Sweden)

    Cīırulis Jānis

    2015-12-01

    Full Text Available A class of (right Rickart rings, called strong, is isolated. In particular, every Rickart *-ring is strong. It is shown in the paper that every strong Rickart ring R admits a binary operation which turns R into a right normal band having an upper bound property with respect to its natural order ≤; such bands are known as right normal skew nearlattices. The poset (R, ≤ is relatively orthocomplemented; in particular, every initial segment in it is orthomodular.

  7. Saturn’s ring temperatures at equinox

    Science.gov (United States)

    Spilker, Linda J.; Ferrari, C.; Morishima, R.

    2013-10-01

    Modeling the thermal emission of Saturn's rings is challenging due to the numerous heating sources as well as the structural properties of the disk and of the particles that are closely related. At equinox, however, the main rings are externally heated by Saturn alone and the problem is somewhat simplified. We test the abilities of our current models to reproduce the temperatures observed with the Cassini CIRS instrument around equinox in August 2009. A simple semi-analytic model which includes mutual shadowing effects can mostly explain the radial profile of the equinox ring temperatures, except the model predicts lower temperatures than those observed for the A ring. The temperature variation at a given saturnocentric radius is primarily caused by observational geometry variations relative to Saturn. The observed temperature increases with decreasing Saturn-ring-observer angle. In addition, we found evidence that the leading hemispheres of particles are warmer than the trailing hemispheres at least for the C ring and probably for the A and B rings as well. This is explained if some fraction of particles has spin rates lower than the synchronous rotation rate as predicted by N-body simulations. The spin model for a monolayer ring (Ferrari, C., Leyrat, C., 2006, Astron. Astrophys. 447, 745-760) can fit the temperature variations with spacecraft longitude observed in the C ring with currently known thermal properties and a mixing of slow and fast rotators. The multilayer model (Morishima, R., Salo, H., Ohtsuki, K., 2009, Icarus 201, 634-654) can reproduce the temperatures of the B and C rings but gives A ring temperatures that are significantly lower than those observed as does the simple semi-analytic model. More advanced models which take into account self-gravity wakes may explain the A ring temperature behavior.

  8. Parameter Scan for the CLIC Damping Rings

    CERN Document Server

    Papaphilippou, Y; Korostelev, M

    2008-01-01

    Triggered by the RF frequency reduction of the CLIC main linac cavities, the damping ring parameters had to be reevaluated and the rings performance adapted to the new luminosity requirements. In view of a staged approach for reaching the ultimate energy of the collider, the dependence of the rings output emittances under the influence of Intrabeam Scattering is evaluated with respect to different beam characteristics such as bunch population, beam energy, coupling and longitudinal beam characteristics.

  9. New cytotoxic phloroglucinol derivatives from Agrimonia pilosa.

    Science.gov (United States)

    Tang, Lan; Fu, Lulu; Lu, Chenghua; Hou, Xiaorong; Shan, Weiguang; Zhan, Zhajun

    2017-04-01

    Three new phloroglucinol derivatives, namely agripinol A-C (1-3), were isolated from Agrimonia pilosa Ledeb, along with two known ones (4-5). Their structures were characterized by spectroscopic methods, including MS and NMR spectroscopic techniques. The absolute configurations of the new compounds were unambiguously established by single crystal X-ray diffraction analyses. In the cytotoxicity assay, all compounds exhibited more potent cytotoxic activities against HCT-116, MDA-MB-231 and PC-3, as compared with the positive control fluorouracil. Copyright © 2017. Published by Elsevier B.V.

  10. Cytotoxicity of Two Triterpenoids from Nigella glandulifera

    Directory of Open Access Journals (Sweden)

    Erxi Wu

    2006-09-01

    Full Text Available During an investigation of antitumor substances from Nigella glandulifera Freyn et Sint. (Ranunculaceae the cytotoxicity of two oleanane triterpene saponins isolated from the seeds of this species, kalopanaxsaponins A and I, was evaluated against HepG2, drug resistant HepG2 (R-HepG2 (two hepatocyte cell lines and primary cultured normal mouse hepatocytes. Evident cytotoxic activities were observed. Morphological observations and cell cycle analysis suggest that these compounds inhibit the proliferation of hepatoma by inducing apoptosis and consequently kalopanaxsaponins A and I may be potential therapeutic agents for the treatment of parental and drug resistant hepatoma.

  11. Biotransformation and Cytotoxic Activity of Guaiacol Dimer

    Directory of Open Access Journals (Sweden)

    Galuh Widiyarti

    2014-07-01

    Full Text Available Guaiacol, a phenolic compound is known as an anticancer. Dimerization of guaiacol has been done by biotransformation using peroxidase enzyme as biocatalyst. This enzyme was isolated from Indonesian plant, kailan (Brassica oleraceae var. alboglabra. Analysis of dimerization product was carried out by TLC, IR, LC-MS, and NMR. Whilst analysis of in-vitro cytotoxic activity was carried out by MTT method against breast cancer T47D and MCF7 cells. The result showed that the dimerization reaction gave O-para dehydroguaiacol. The in-vitro cytotoxic activity analysis showed that O-para dehydroguaiacol compound has potency as anti-breast cancer.

  12. Cytotoxic Aaptamines from Malaysian Aaptos aaptos

    Directory of Open Access Journals (Sweden)

    Kee Cheng Ling

    2008-12-01

    Full Text Available In a preliminary screen, Aaptos aaptos showed significant cytotoxic activity towards a panel of cell lines and was thus subjected to bioassay-guided isolation of the bioactive constituents. In addition to the known aaptamine, two new derivatives of the alkaloid were isolated from the bioactive chloroform fraction of the crude methanolic extract. Detailed analysis by NMR and mass spectroscopy enabled their identification to be 3-(phenethylaminodemethyl(oxyaaptamine and 3-(isopentylaminodemethyl(oxy aaptamine. The cytotoxic activities of the three alkaloids were further evaluated against CEM-SS cells.

  13. Cytotoxicity associated with prolonged room temperature storage of serum and proposed methods for reduction of cytotoxicity.

    Science.gov (United States)

    Shiraishi, Rikiya; Hirayama, Norio

    2015-12-01

    Canine serum preserved at room temperature (25°C) for longer than 24h is known to exhibit significant cytotoxicity. This phenomenon is one of the major reasons for the failure of virus neutralization tests. In this study, a method for reducing this cytotoxicity was investigated by applying several treatments to dog, cat and human serum prior to room temperature storage. Additionally, the identity of the cytotoxic factor generated during room temperature storage was investigated. Heat-inactivation at 56°C or 65°C and the addition of protease inhibitor prior to storage were found to be effective for reducing cytotoxicity in the serum. Furthermore, heat-inactivation at 65°C reduced the cytotoxicity that was induced under room temperature storage. Several protein factors in serum were suspected to play a role in the observed cytotoxicity. According to this study, the membrane-attack-complex in serum was not involved in the cytotoxicity. This study provides useful information for development and improvement of cell culture and virus neutralization tests. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Correlation between luminescence intensity and cytotoxicity in cell-based cytotoxicity assay using luciferase.

    Science.gov (United States)

    Wakuri, S; Yamakage, K; Kazuki, Y; Kazuki, K; Oshimura, M; Aburatani, S; Yasunaga, M; Nakajima, Y

    2017-04-01

    The luciferase reporter assay has become one of the conventional methods for cytotoxicity evaluation. Typically, the decrease of luminescence expressed by a constitutive promoter is used as an index of cytotoxicity. However, to our knowledge, there have been no reports of the correlation between cytotoxicity and luminescence intensity. In this study, to accurately verify the correlation between them, beetle luciferase was stably expressed in human hepatoma HepG2 cells harboring the multi-integrase mouse artificial chromosome vector. We showed that the cytotoxicity assay using luciferase does not depend on the stability of luciferase protein and the kind of constitutive promoter. Next, HepG2 cells in which green-emitting beetle luciferase was expressed under the control of CAG promoter were exposed to 58 compounds. The luminescence intensity and cytotoxicity curves of cells exposed to 48 compounds showed similar tendencies, whereas those of cells exposed to 10 compounds did not do so, although the curves gradually approached each other with increasing exposure time. Finally, we demonstrated that luciferase expressed under the control of a constitutive promoter can be utilized both as an internal control reporter for normalizing a test reporter and for monitoring cytotoxicity when two kinds of luciferases are simultaneously used in the cytotoxicity assay. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Design of Piston Ring Friction Tester Apparatus

    DEFF Research Database (Denmark)

    Klit, Peder

    2006-01-01

    One of the major prerequisites for calculating piston ring friction is a good description of the tribological situation. Piston rings operate in three different lubrication regimes and the theoretical models should be capable to describe this. A very important condition for describing the frictio......One of the major prerequisites for calculating piston ring friction is a good description of the tribological situation. Piston rings operate in three different lubrication regimes and the theoretical models should be capable to describe this. A very important condition for describing...... the frictional behavior of a piston ring correctly is knowledge about the amount of lubricant present. For piston rings the external load may be established by measuring the pressure distribution, i.e. the pressure drop in the piston ring package. Speed and temperature may also be established. The amount...... available is reflected in the friction absorbed in the bearing. The following properties will be measured: Oil fillm thickness - along liner (axial variation), oil film thickness - along piston ring (circumferential variation), piston tilt, temperature of piston rings and liner, pressure at piston lands...

  16. Forandringslæring med autismediagnoser?

    DEFF Research Database (Denmark)

    Gustafson, Kari Ingrid; Mørck, Line Lerche

    2013-01-01

    Rasmus’ ændringer i læring, selvforståelse og tilhørsforhold perspektiveres med andre ASF-diagnostiseredes læring udforsket bl.a. gennem gruppeinterviews i regi af Asperger-foreningen. Artiklen byder således på et alternativ i form af at forstå forandringslæring som overskridende læring, med langt større...... hvor fx Asperger-foreningen, lærere og skolebørns- og unges-fællesskaber, samt forældrene er vigtige aktører i overskridelsen af marginalisering....

  17. Corneal iron ring after hyperopic photorefractive keratectomy.

    Science.gov (United States)

    Bilgihan, K; Akata, F; Gürelik, G; Adigüzel, U; Akpinar, M; Hasanreisoğlu, B

    1999-05-01

    To report the incidence and course of corneal iron deposition after hyperopic photorefractive keratectomy (PRK). Gazi University, Medical School, Department of Ophthalmology, Ankara, Turkey. Between January 1995 and December 1997, 62 eyes had PRK to correct hyperopia. Nine eyes developed corneal iron ring 5 to 8 months (mean 6.25 months +/- 1.3 [SD]) after PRK for hyperopia. The rings persisted during the mean follow-up of 19 +/- 11.09 months. The ring-shaped iron deposition after PRK for hyperopia must be differentiated from the Fleischer ring. Our results suggest that the slitlamp findings of peripheral corneal iron deposition in hyperopic PRK patients correlate with achieved correction.

  18. Multiplication modules over non-commutative rings

    International Nuclear Information System (INIS)

    Tuganbaev, A A

    2003-01-01

    It is proved that each submodule of a multiplication module over a regular ring is a multiplicative module. If A is a ring with commutative multiplication of right ideals, then each projective right ideal is a multiplicative module, and a finitely generated A-module M is a multiplicative module if and only if all its localizations with respect to maximal right ideals of A are cyclic modules over the corresponding localizations of A. In addition, several known results on multiplication modules over commutative rings are extended to modules over not necessarily commutative rings

  19. Status of the SLC damping rings

    International Nuclear Information System (INIS)

    Hutton, A.M.; Davies-White, W.A.; Delahaye, J.P.

    1985-06-01

    Electron beams of full design energy 1.21 GeV and nearly full design intensity 4 x 10 10 particles/pulse (design 5 x 10 10 ) have been extracted from the Stanford Linac and successfully stored in the electron damping ring. Beams of less intensity have been extracted from the ring and reinjected into the Linac. The present intensity limits are not thought to be fundamental. The operating experience with the electron ring and the status of the construction of the positron ring will be discussed. 11 refs., 1 fig., 2 tabs

  20. Incipient cytotoxicity: A time-independent measure of cytotoxic potency in vitro.

    Science.gov (United States)

    Gülden, Michael; Kähler, Daria; Seibert, Hasso

    2015-09-01

    Time is an important determinant of toxicity but largely ignored in in vitro toxicity assays where exposure times chosen are rather arbitrary. To investigate the impact of time on the cytotoxic potency of chemicals in vitro, the concentration dependent cytotoxic action of selected chemicals (surfactants, metals, oxidative stressors, a mitochondrial poison) was determined after various exposure times (1-72 h) in cultures of Balb/c 3T3 cells. Time affected the cytotoxic potency as well as the cytotoxic efficacy. The median cytotoxic concentrations, EC50, decreased and in most cases approached an "incipient" value, EC50,∞, within 72 h. Cytotoxicity due to mitochondrial insult occurred after a threshold time which was dependent on the medium glucose concentration. Within the chemicals studied the extent of potency change with time ranged from 3- to >1000-fold and the "time to incipient cytotoxicity", tic, from 4 to >72 h. Hence, also the relative cytotoxic potencies depend on exposure time. Ignoring this may lead to severe bias in toxicological hazard and risk assessment. Therefore it is recommended to determine the incipient cytotoxic potency of chemical compounds, represented by, e.g., the incipient median effect (EC50,∞), no effect (NEC∞) or lowest effect concentrations (LEC∞) instead of measures obtained after arbitrary exposure times. If this is not possible, the 72 h-potency measurements appear to be useful surrogates. These time-independent incipient potency values can be reasonably compared between substances, endpoints, cells and biological test systems and may serve to define points of departure for quantitative in vitro-in vivo extrapolations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. The Conversion of Wiswesser Line Notations to Ring Codes. I. The Conversion of Ring Systems

    Science.gov (United States)

    Granito, Charles E.; And Others

    1972-01-01

    The computerized conversion of Wiswesser Line Notations to Ring Codes, using a two-part approach, and the set of computer programs generated for the conversion of ring systems are described. (9 references) (Author)

  2. Mechanical support of a ceramic gas turbine vane ring

    Science.gov (United States)

    Shi, Jun; Green, Kevin E.; Mosher, Daniel A.; Holowczak, John E.; Reinhardt, Gregory E.

    2010-07-27

    An assembly for mounting a ceramic turbine vane ring onto a turbine support casing comprises a first metal clamping ring and a second metal clamping ring. The first metal clamping ring is configured to engage with a first side of a tab member of the ceramic turbine vane ring. The second metal clamping ring is configured to engage with a second side of the tab member such that the tab member is disposed between the first and second metal clamping rings.

  3. Ring opening metathesis polymerization catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Grubbs, R.H.; Johnson, L.K.; Novak, B.M.; Hillmyer, M.; Benedicto, A.; France, M.; Nguyen, S.T. [California Institute of Technology, Pasadena, CA (United States)

    1993-12-31

    Over the past eight years, a number of new catalysts for the ring opening metathesis polymerization of cyclic olefins have been developed. These catalysts are simple organometallic complexes containing metal carbon multiple bonds that in most cases polymerize olefins by a living process. These catalysts have been used to prepare a family of near monodispersed and structurally homogeneous polymers, a series of telechelic polymers with controlled molecular weight and functionality and triblock polymers with segments with potentially interesting electronic properties. A series of new group VIII catalysts are being developed that allow a wide range of functionality to be incorporated into the polymer side chains. The same catalysts can also be used in the synthesis of fine chemicals.

  4. Main ring transition crossing simulations

    International Nuclear Information System (INIS)

    Kourbanis, I.; Ng, King-Yuen.

    1990-10-01

    We used ESME to simulate transition crossing in the Main Ring (MR). For the simulations, we followed the MR 29 cycle used currently for bar p production with a flat top of 120 GeV. In Sect. II, some inputs are discussed. In Sect. III, we present simulations with space charge turned off so that the effect of nonlinearity can be studied independently. When space charge is turned on in Sect. IV, we are faced with the problem of statistical errors due to binning, an analysis of which is given in the Appendices. Finally in Sects. V and VI, the results of simulations with space charge are presented and compared with the experimental measurements. 7 refs., 6 figs

  5. Low-emittance Storage Rings

    CERN Document Server

    Wolski, Andrzej

    2014-01-01

    The effects of synchrotron radiation on particle motion in storage rings are discussed. In the absence of radiation, particle motion is symplectic, and the beam emittances are conserved. The inclusion of radiation effects in a classical approximation leads to emittance damping: expressions for the damping times are derived. Then, it is shown that quantum radiation effects lead to excitation of the beam emittances. General expressions for the equilibrium longitudinal and horizontal (natural) emittances are derived. The impact of lattice design on the natural emittance is discussed, with particular attention to the special cases of FODO-, achromat- and theoretical-minimum-emittance-style lattices. Finally, the effects of betatron coupling and vertical dispersion (generated by magnet alignment and lattice tuning errors) on the vertical emittance are considered.

  6. What confines the rings of Saturn?

    Science.gov (United States)

    Tajeddine, Radwan; Nicholson, Philip D.; El Moutamid, Maryame; Longaretti, Pierre-Yves; Burns, Joseph A.

    2017-10-01

    The viscous spreading of planetary rings is believed to be counteracted by satellite torques, either through an individual resonance or through overlapping resonances (when the satellite is close to the ring edge). For the A ring of Saturn, it has been commonly believed that the satellite Janus alone can prevent the ring from spreading via its 7:6 Lindblad resonance. We discuss this common misconception and show that, in reality, the A ring is confined by the contributions from the group of satellites Pan, Atlas, Prometheus, Pandora, Janus, Epimetheus, and Mimas, whose resonances gradually decrease the angular momentum flux transported outward through the ring via density and bending waves. We further argue that this decrease in angular momentum flux occurs through the mechanism of ‘flux reversal’.We find that the Janus 7:6 torque is relatively feeble, as is the comparable torque of the nearby small satellite Atlas, each amounting to less than one-tenth of the angular momentum transport carried by the A ring. But the cumulative torques of the many other satellite resonances in the A ring sufficiently reduce the angular momentum flux through the rings so that the torques due to Janus and Atlas are effective in confining the outer edge of the ring.Furthermore, we use the magnitude of the satellites’ resonance torques to estimate the effective viscosity profile across the A ring, showing that it decreases from ~50 cm2 s-1 at the inner edge to less than ~11 cm2 s-1 at the outer edge. The gradual estimated decrease of the angular momentum flux and effective viscosity are roughly consistent with results obtained by balancing the shepherding torques from Pan and Daphnis with the viscous torque at the edges of the Encke and Keeler gaps, as well as the edge of the A ring.On the other hand, the Mimas 2:1 Lindblad resonance alone seems to be capable of confining the edge of the B ring, and contrary to the situation in the A ring, we show that the effective viscosity

  7. Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin.

    Science.gov (United States)

    Yeh, Lee-Chuan C; Banerjee, Asok; Prasad, Veena; Tuszynski, Jack A; Weis, Alexander L; Bakos, Tamas; Yeh, I-Tien; Ludueña, Richard F; Lee, John C

    2016-02-01

    The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the β subunit. There are many isotypes of β-tubulin and their distributions differ among different tissues. The βIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on βIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing βIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the βIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.

  8. Analysis of Dermal Papilla Cell Interactome Using STRING Database to Profile the ex Vivo Hair Growth Inhibition Effect of a Vinca Alkaloid Drug, Colchicine

    Directory of Open Access Journals (Sweden)

    Ching-Wu Hsia

    2015-02-01

    Full Text Available Dermal papillae (DPs control the formation of hair shafts. In clinical settings, colchicine (CLC induces patients’ hair shedding. Compared to the control, the ex vivo hair fiber elongation of organ cultured vibrissa hair follicles (HFs declined significantly after seven days of CLC treatment. The cultured DP cells (DPCs were used as the experimental model to study the influence of CLC on the protein dynamics of DPs. CLC could alter the morphology and down-regulate the expression of alkaline phosphatase (ALP, the marker of DPC activity, and induce IκBα phosphorylation of DPCs. The proteomic results showed that CLC modulated the expression patterns (fold > 2 of 24 identified proteins, seven down-regulated and 17 up-regulated. Most of these proteins were presumably associated with protein turnover, metabolism, structure and signal transduction. Protein-protein interactions (PPI among these proteins, established by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING database, revealed that they participate in protein metabolic process, translation, and energy production. Furthermore, ubiquitin C (UbC was predicted to be the controlling hub, suggesting the involvement of ubiquitin-proteasome system in modulating the pathogenic effect of CLC on DPC.

  9. VUV optical ring resonator for Duke storage ring free electron laser

    Energy Technology Data Exchange (ETDEWEB)

    Park, S.H.; Litvinenko, V.N.; Madey, J.M.J. [Duke Univ., Durham, NC (United States)] [and others

    1995-12-31

    The conceptual design of the multifaceted-mirror ring resonator for Duke storage ring VUV FEL is presented. The expected performance of the OK-4 FEL with ring resonator is described. We discuss in this paper our plans to study reflectivity of VUV mirrors and their resistivity to soft X-ray spontaneous radiation from OK-4 undulator.

  10. Electron beam cooling at a magnetic storage ring, TARN II, and an electrostatic storage ring

    International Nuclear Information System (INIS)

    Tanabe, Tetsumi

    2006-01-01

    At the High Energy Accelerator Research Organization (KEK), a magnetic storage ring, TARN II, with an electron cooler was operated from 1989 to 1999, while an electrostatic storage ring with a small electron cooler has been operational since 2000. In this paper, the electron cooling at TARN II and the electrostatic storage ring is described. (author)

  11. Cytotoxicity potentials of eleven Bangladeshi medicinal plants.

    Science.gov (United States)

    Khatun, Amina; Rahman, Mahmudur; Haque, Tania; Rahman, Md Mahfizur; Akter, Mahfuja; Akter, Subarna; Jhumur, Afrin

    2014-01-01

    Various forms of cancer are rising all over the world, requiring newer therapy. The quest of anticancer drugs both from natural and synthetic sources is the demand of time. In this study, fourteen extracts of different parts of eleven Bangladeshi medicinal plants which have been traditionally used for the treatment of different types of carcinoma, tumor, leprosy, and diseases associated with cancer were evaluated for their cytotoxicity for the first time. Extraction was conceded using methanol. Phytochemical groups like reducing sugars, tannins, saponins, steroids, gums, flavonoids, and alkaloids were tested using standard chromogenic reagents. Plants were evaluated for cytotoxicity by brine shrimp lethality bioassay using Artemia salina comparing with standard anticancer drug vincristine sulphate. All the extracts showed potent to moderate cytotoxicity ranging from LC50 2 to 115 µg/mL. The highest toxicity was shown by Hygrophila spinosa seeds (LC50 = 2.93 µg/mL) and the lowest by Litsea glutinosa leaves (LC50 = 114.71 µg/mL) in comparison with standard vincristine sulphate (LC50 = 2.04 µg/mL). Among the plants, the plants traditionally used in different cancer and microbial treatments showed highest cytotoxicity. The results support their ethnomedicinal uses and require advanced investigation to elucidate responsible compounds as well as their mode of action.

  12. Cytotoxicity Potentials of Eleven Bangladeshi Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Amina Khatun

    2014-01-01

    Full Text Available Various forms of cancer are rising all over the world, requiring newer therapy. The quest of anticancer drugs both from natural and synthetic sources is the demand of time. In this study, fourteen extracts of different parts of eleven Bangladeshi medicinal plants which have been traditionally used for the treatment of different types of carcinoma, tumor, leprosy, and diseases associated with cancer were evaluated for their cytotoxicity for the first time. Extraction was conceded using methanol. Phytochemical groups like reducing sugars, tannins, saponins, steroids, gums, flavonoids, and alkaloids were tested using standard chromogenic reagents. Plants were evaluated for cytotoxicity by brine shrimp lethality bioassay using Artemia salina comparing with standard anticancer drug vincristine sulphate. All the extracts showed potent to moderate cytotoxicity ranging from LC50 2 to 115 µg/mL. The highest toxicity was shown by Hygrophila spinosa seeds (LC50=2.93 µg/mL and the lowest by Litsea glutinosa leaves (LC50=114.71 µg/mL in comparison with standard vincristine sulphate (LC50=2.04 µg/mL. Among the plants, the plants traditionally used in different cancer and microbial treatments showed highest cytotoxicity. The results support their ethnomedicinal uses and require advanced investigation to elucidate responsible compounds as well as their mode of action.

  13. Cytotoxicity of poly(p-phenylenediamine)

    Czech Academy of Sciences Publication Activity Database

    Kuceková, Z.; Rejmontová, P.; Humpolíček, P.; Kašpárková, V.; Bober, Patrycja; Sáha, P.; Stejskal, Jaroslav

    2017-01-01

    Roč. 71, č. 2 (2017), s. 367-372 ISSN 0366-6352 R&D Projects: GA ČR(CZ) GA13-00270S Institutional support: RVO:61389013 Keywords : cytotoxicity * poly(p-phenylenediamine) * mouse embryonic fibroblasts Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 1.258, year: 2016

  14. SYNTHESIS AND CYTOTOXICITY OF NOVEL LIGNANS

    NARCIS (Netherlands)

    Middel, O; Woerdenbag, H.J.; van Uden, W.; van Oeveren, A.; Jansen, J.F.G.A.; Feringa, B.L.; Konings, A.WT; Pras, N.; Kellogg, R.M

    1995-01-01

    In this study the syntheses of 11 novel lignans are described. Their cytotoxicities are studied in GLC(4), a human small cell lung carcinoma cell line, using the microculture tetrazolium (MTT) assay. Ten of these compounds were substituted with a menthyloxy group on the 5-position of the lactone.

  15. Phytochemical and cytotoxic analysis of Pharthenium hysterophosis ...

    African Journals Online (AJOL)

    Parthenium hysterophorus is a well known medicinal plant widely used traditionally in the treatment of various diseases and as a constituent of various drugs, and in phytotherapy. The current study was designed to investigate the phytochemical screening and cytotoxic capacity of methanolic and n-hexane extract of P.

  16. Synthesis and cytotoxic evaluation of isoxazoles an

    Indian Academy of Sciences (India)

    tetrazolium bromide] cell proliferation assay was used to evaluate the cytotoxic activity of the synthesized compounds against COLO320 adenocarcinoma col- orectal cancer cell lines.6 COLO320 cancer cell line was maintained in complete tissue culture medium. RPMI with 10% Fetal Bovine Serum and 2 mM L-. Glutamine ...

  17. Randomized anticancer and cytotoxicity activities of Guibourtia ...

    African Journals Online (AJOL)

    Materials and Methods: The plants were screened for the presence of coumarins, alkaloids, flavonoids, anthraquinones, steroids and terpenoids using thin layer chromatography. Anticancer screening was performed on a panel of three cancer cell lines, while cytotoxicity was determined using a human fibroblast cell line, ...

  18. Anticonvulsant, Antimicrobial and Cytotoxic Activities of Berberis ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anticonvulsant, antimicrobial and cytotoxic activities of Berberis calliobotrys. Methods: The powdered plant material (10 kg) was extracted thrice with methanol (3 × 12 L) by dipping for seven days. The methanol extract was concentrated to dryness under reduced pressure, and then successively ...

  19. Cytotoxicity of Nanoliposomal Cisplatin Coated with Synthesized ...

    African Journals Online (AJOL)

    Purpose: To evaluate the cytotoxicity of pegylated nanoliposomal cisplatin on human ovarian cancer cell line A2780CP. Methods: Synthesized methoxypolyethylene glycol (mPEG) propionaldehyde was characterized by 1Hnuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FTIR) and used ...

  20. The antioxidant properties, cytotoxicity and monoamine oxidase ...

    African Journals Online (AJOL)

    Tarchonanthus camphoratus (camphor bush) has been widely used for numerous medicinal purposes. The aim of the present study was to evaluate the antioxidant properties, cytotoxicity and monoamine oxidase inhibition activities of the crude dichloromethane leaf extract of T. camphoratus. The antioxidant activities were ...

  1. Synthesis, characterisation, nuclease and cytotoxic activity of ...

    Indian Academy of Sciences (India)

    GULZAR A BHAT

    2018-02-07

    Feb 7, 2018 ... Synthesis, characterisation, nuclease and cytotoxic activity of phosphate-free and phosphate-containing copper. 4 -(N-methylpyridinium)-2,2 :6 ,2 terpyridine complexes. GULZAR A BHATa, RAIHANA MAQBOOLb and RAMASWAMY MURUGAVELa,∗. aDepartment of Chemistry, Indian Institute of ...

  2. Rifampicin: Cytotoxic and Genotoxic Action | Olufunsho | Nigerian ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the cytotoxic and genotoxic effects of Rif to better understand its mutagenicity. The study was carried out using three methods: Standard Allium cepa (Linn.) assay, modified Ames test (which is a modification of the standard Ames assay) and micronucleus test (an in vivo method ...

  3. Development of Novel Bis(indolyl)-hydrazide-Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells.

    Science.gov (United States)

    Das Mukherjee, Dipanwita; Kumar, N Maruthi; Tantak, Mukund P; Das, Amlan; Ganguli, Arnab; Datta, Satabdi; Kumar, Dalip; Chakrabarti, Gopal

    2016-05-31

    The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesize novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognized NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue-purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells, normal human lung fibroblasts (WI38) and peripheral blood mononuclear cells (PBMC) with IC50 values of ∼2, 48.5, and 62 μM, respectively. Thus, the relatively high cytotoxicity of NMK-BH3 toward lung carcinoma (A549) cells over normal lung fibroblasts (WI38) and PBMC confers a therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot, and immunofluorescence studies in the A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarization, and apoptosis by depolymerizing the cellular interphase and spindle microtubules. Consistent with these observations, study in cell free system revealed that NMK-BH3 inhibited the microtubule assembly with an IC50 value of ∼7.5 μM. The tubulin-ligand interaction study using fluorescence spectroscopy indicated that NMK-BH3 exhibited strong and specific tubulin binding with a dissociation constant of ∼1.4 μM at a single site, very close to colchicine site, on β-tubulin. Collectively, these findings explore the cytotoxic potential of NMK-BH3 by targeting the microtubules and inspire its development as a potential candidate for lung cancer chemotherapy.

  4. Phenolics, Antiradical Assay and Cytotoxicity of Processed Mango ...

    African Journals Online (AJOL)

    Phenolics, Antiradical Assay and Cytotoxicity of Processed Mango ( Mangifera indica ) and Bush Mango ( Irvingia gabonensis ) Kernels. ... Nigerian Food Journal ... Phenolic constituents (total phenols, flavonoids, tannins, and anthocyanins), comparative antiradical potency and cytotoxicity of processed mango (Mangifera ...

  5. A cytotoxic serine proteinase isolated from mouse submandibular gland.

    Science.gov (United States)

    Shimamura, T; Nagumo, N; Ikigai, H; Murakami, K; Okubo, S; Toda, M; Ohnishi, R; Tomita, M

    1989-08-01

    We have isolated a novel cytotoxic factor from the submandibular glands of male BALB/c mice by Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. The cytotoxic factor is a serine proteinase, which belongs to the mouse glandular kallikrein (mGK) family, with an Mr of approximately 27,000. The purified serine proteinase showed cytotoxic activity against mouse thymocytes in a dose-dependent manner, and a serine proteinase inhibitor, diisopropyl fluorophosphate, blocked its cytotoxic activity.

  6. Radiation vulcanized natural rubber latex is not cytotoxic

    International Nuclear Information System (INIS)

    Nakamura, Akitada; Ikarashi, Y.; Tsuchiya, T.; Kaniwa, M.

    1990-01-01

    It has been reported that urethritis and/or urethral strictures caused by urinary catheters relates to cytotoxicities of their materials, and that natural rubber latex (NRL) materials often show the strong cytotoxicities. This paper reports the cytotoxicity testing method using chinese hamster V79 cultured cells, clarifies that the toxicities of NRLs vulcanized by the conventional processes are due mainly to the contents of zinc dialkyldithiocarbamates in the materials, and that the cytotoxicity of radiation vulcanized NRL (RVNRL) is very weak. (author)

  7. Two cases of halo scalp ring.

    Science.gov (United States)

    Douri, Thaer Hasan

    2016-11-15

    Halo scalp ring (HSR) is a rare form of non-scarring annular alopecia that is attributed to caput succedaneum. It arises perinatally because of prolonged pressure on the scalp by the cervix during or before the delivery. We report two new cases of halo scalp ring in full term pregnancy - newborns.

  8. Two cases of halo scalp ring

    OpenAIRE

    Douri, Thaer Hasan

    2016-01-01

    Halo scalp ring (HSR) is a rare form of non-scarring annular alopecia that is attributed to caput succedaneum. It arises perinatally because of prolonged pressure on the scalp by the cervix during or before the delivery. We report two new cases of halo scalp ring in full term pregnancy - newborns.

  9. Local duality for 2-dimensional local ring

    Indian Academy of Sciences (India)

    We prove a local duality for some schemes associated to a 2-dimensional complete local ring whose residue field is an -dimensional local field in the sense of Kato–Parshin. Our results generalize the Saito works in the case =0 and are applied to study the Bloch–Ogus complex for such rings in various cases.

  10. Hawking radiation of black rings from anomalies

    International Nuclear Information System (INIS)

    Chen Bin; He Wei

    2008-01-01

    We derive Hawking radiation of five-dimensional black rings from gauge and gravitational anomalies using the method proposed by Robinson and Wilczek. We find, as in the black hole case, that the problem could reduce to a (1+1)-dimensional field theory and the anomalies result in correct Hawking temperature for neutral, dipole and charged black rings

  11. Local duality for 2-dimensional local ring

    Indian Academy of Sciences (India)

    dimensional complete local ring whose residue field is an n-dimensional local field in the sense of. Kato–Parshin. Our results generalize the Saito works in the case n = 0 and are applied to study the Bloch–Ogus complex for such rings in various cases.

  12. Counteracting ring formation in rotary kilns

    NARCIS (Netherlands)

    Pisaroni, M.; Sadi, R.; Lahaye, D.

    Avoiding the formation of rings in rotary kilns is an issue of primary concern to the cement production industry. We developed a numerical combustion model that revealed that in our case study rings are typically formed in zones of maximal radiative heat transfer. This local overheating causes the

  13. The King's Ring: A Matter of Trust

    DEFF Research Database (Denmark)

    Sterrett, Joseph William

    2018-01-01

    This essay examines the material and social effects of an exchange of trust between a king, Henry VIII, and his counsellor, Thomas Cranmer in Shakespeare and Fletcher’s All is True. The ring that the King gives Cranmer is both nothing and everything: nothing in that it could be anything, any ring...

  14. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...

  15. Coefficient rings of formal group laws

    International Nuclear Information System (INIS)

    Buchstaber, V M; Ustinov, A V

    2015-01-01

    We describe the coefficient rings of universal formal group laws which arise in algebraic geometry, algebraic topology and their application to mathematical physics. We also describe the homomorphisms of these coefficient rings coming from reductions of one formal group law to another. The proofs are based on the number-theoretic properties of binomial coefficients. Bibliography: 37 titles

  16. Ring chromosome 13 and ambiguous genitalia.

    Science.gov (United States)

    Ozsu, Elif; Yeşiltepe Mutlu, Gül; Ipekçi, Belkıs

    2014-01-01

    Ambiguous genitalia, known to be associated with sex chromosome disorders, may also be seen with autosomal chromosome anomalies. Herein, we report a case with ambiguous genitalia and ring chromosome 13. Ring chromosome 13 is a rare genetic anomaly in which the loss of genetic material determines the clinical spectrum.

  17. Ring Chromosome 13 and Ambiguous Genitalia

    OpenAIRE

    Özsu, Elif; Yeşiltepe Mutlu, Gül; İpekçi, Belkıs

    2014-01-01

    Ambiguous genitalia, known to be associated with sex chromosome disorders, may also be seen with autosomal chromosome anomalies. Herein, we report a case with ambiguous genitalia and ring chromosome 13. Ring chromosome 13 is a rare genetic anomaly in which the loss of genetic material determines the clinical spectrum.

  18. On P-coherent endomorphism rings

    Indian Academy of Sciences (India)

    A ring is called right -coherent if every principal right ideal is finitely presented. Let M R be a right -module. We study the -coherence of the endomorphism ring of M R . It is shown ... Author Affiliations. Li-Xin Mao1. Institute of Mathematics, Nanjing Institute of Technology, Nanjing 211167, People's Republic of China ...

  19. The Fine Structure of Herman Rings

    DEFF Research Database (Denmark)

    Fagella, Nuria; Henriksen, Christian

    2017-01-01

    We study the geometric structure of the boundary of Herman rings in a model family of Blaschke products of degree 3 (up to quasiconformal deformation). Shishikura’s quasiconformal surgery relates the Herman ring to the Siegel disk of a quadratic polynomial. By studying the regularity properties...

  20. On the nonlinear modeling of ring oscillators

    KAUST Repository

    Elwakil, Ahmed S.

    2009-06-01

    We develop higher-order nonlinear models of three-stage and five-stage ring oscillators based on a novel inverter model. The oscillation condition and oscillation frequency are derived and compared to classical linear model analysis. Two important special cases for five-stage ring oscillators are also studied. Numerical simulations are shown. © 2009 World Scientific Publishing Company.