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Sample records for anti-proliferative substance taurolidine

  1. Oral administration of the anti-proliferative substance taurolidine has no impact on dextran sulfate sodium-induced colitis-associated carcinogenesis in mice

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    Chromik Ansgar

    2010-01-01

    Full Text Available Background: New chemopreventive strategies for ulcerative colitis (UC-associated dysplasia and cancer have to be evaluated. Taurolidine (TRD has anti-inflammatory, anti-proliferative and anti-neoplastic properties with almost absent toxicity. The aim of the study was to determine whether TRD decreases dysplasia in the well-characterized Dextran Sulfate Sodium - Azoxymethane (DSS-AOM animal model for UC-associated carcinogenesis. Material and Methods: The DSS-AOM model of carcinogenesis was induced in female inbred C57BL/6 mice. Half of the mice were treated with TRD, the other served as control. After 100 days macroscopic, histological and immunhistochemical (β-Catenin, E-Cadherin, SOX9, Ki-67, Cyclin-D1 examination of the colon was performed. Results: Incidence, multiplicity, grading and growth pattern of adenomas did not differ significantly between TRD and control group. In all animals, inflammatory changes were absent. Immunhistochemistry revealed increased expression of Ki-67, β-catenin, SOX9 and Cyclin-D1 in adenomas compared to normal mucosa - without significant difference between TRD and control treatment. Conclusion: Oral administration of TRD has no impact on DSS-induced colitis-associated carcinogenesis. However, SOX9 and Cyclin-D1 representing key members of the Wnt pathway have not yet been described in the DSS-AOM model of carcinogenesis - underlining the importance of this oncogenic pathway in this setting.

  2. The antibacterial substance, taurolidine in the second/third-line treatment of very advanced stage IV melanoma including brain metastases: results of a phase 2, open-label study.

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    Imhof, Laurence; Goldinger, Simone M; Baumann, Katrin; Schad, Karin; French, Lars E; Röthlisberger, Peter; Dummer, Reinhard

    2011-02-01

    The efficacy and tolerability of taurolidine, an antibacterial substance, was evaluated in a phase 2 trial enrolling patients with advanced melanoma. The treatment schedule consisted of daily taurolidine (20 g) administered intravenously for 5 days per week for 3 consecutive weeks followed by 1 week of rest. One cycle comprised of 28 days. A maximum of six cycles could be administered. Sixteen patients were assessable for tumor response, seven of whom had brain metastases. Three patients (18.8%) achieved disease stabilization, including a patient with a primary mucosal melanoma of the nasal cavity who had a marked locoregional response with disease stabilization of the distant metastases. Thirteen patients had disease progression. Median overall survival was 46±1 days. Adverse events were moderate and mainly gastrointestinal. Treatment with taurolidine has no activity in patients with advanced melanoma.

  3. The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death.

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    Stendel, Ruediger; Biefer, Hector Rodriguez Cetina; Dékány, Gabriela Marta; Kubota, Hisashi; Münz, Christian; Wang, Sheng; Mohler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

    2009-02-01

    The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.

  4. Anti-proliferative effects of deflazacort on Nb2 cells as quantitated by formazan production.

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    Adler, R A; Naumann, S A; Mansouri, A; Krieg, R J; Latta, K; Sanders, K M

    1994-01-01

    Prolactin and other lactogenic hormones are mitogenic for the rat T-cell lymphoma line, Nb2. Glucocorticoids have antiproliferative effects on these cells. A limiting feature of experiments utilizing the Nb2 line is their labor-intensive nature. We therefore adapted the commonly used MTT dye proliferation assay for the Nb2 cell line. While rPRL, hPRL, oPRL, hGH, bPL, and to a lesser extent bPRL stimulated the Nb2 cells, hormones without lactogenic activity, rGH and oGH did not. Human serum and rat sera from animals bearing a PRL-secreting tumor stimulated the Nb2 cells in parallel to standards. Glucocorticoids had anti-proliferative effects on Nb2 cells in the presence of half-maximal or maximal PRL doses, as measured by the MTT proliferation assay. It has been claimed that an oxazoline steroid, deflazacort, has anti-inflammatory effects in clinical studies with fewer of the deleterious side-effects common to glucocorticoids. We therefore compared the in vitro anti-proliferative effects of deflazacort with other glucocorticoids. Deflazacort's negative effect on Nb2 cell proliferation was similar to that of cortisol and prednisolone and less than that of dexamethasone. We conclude that the MTT proliferation assay can be used to study both mitogenic and anti-proliferative substances in Nb2 cells. In addition we found that deflazacort acts similarly in vitro to other glucocorticoids.

  5. Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum

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    Guoqing Shi

    2016-05-01

    Full Text Available To explore material basis of in vitro anti-proliferative activity of leukemia cell K562 of petroleum ether phase of product resulting from Galium aparine L. 60% ethanol extraction, the experiment adopts column chromatography combined with thin layer preparation, isolates and purifies petroleum ether, conducts structural identification of obtained single compound and applies MTT method for viability assay of in vitro anti-proliferative activity of leukemia cell K562. Experimental results show that G. aparine L. petroleum ether contains mainly β-sitosterol, daucosterol and dibutyl phthalate and other substances. Under experimental conditions, the three could inhibit the proliferation of leukemia cell K562 with dose-effect and time-effect relationship, of which dibutyl phthalate has strongest activity. Dibutyl phthalate with excellent activity, β-sitosterol with rich content and moderate effect should be the main contributor to its biological activity.

  6. Local and systemic chemotherapy with taurolidine and taurolidine/heparin in colon cancer-bearing rats undergoing laparotomy.

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    Braumann, Chris; Ordemann, Jürgen; Kilian, Maik; Wenger, Frank A; Jacobi, Christoph A

    2003-01-01

    Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 10(4) colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P = 0.05) and of taurolidine/heparin (median 0 mg, P = 0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P = 0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth

  7. Effects of TRAIL and taurolidine on apoptosis and proliferation in human rhabdomyosarcoma, leiomyosarcoma and epithelioid cell sarcoma.

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    Karlisch, C; Harati, K; Chromik, A M; Bulut, D; Klein-Hitpass, L; Goertz, O; Hirsch, T; Lehnhardt, M; Uhl, W; Daigeler, A

    2013-03-01

    Soft tissue sarcomas (STS) are a heterogeneous group of malignant tumours representing 1% of all malignancies in adults. Therapy for STS should be individualised and multimodal, but complete surgical resection with clear margins remains the mainstay of therapy. Disseminated soft tissue sarcoma still represents a therapeutic dilemma. Commonly used chemotherapeutic agents such as doxorubicin and ifosfamide have proven to be effective in fewer than 30% in these cases. Therefore, we tested the apoptotic and anti-proliferative in vitro effects of TNF-related apoptosis-inducing ligand (TRAIL) and taurolidine (TRD) on rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cell lines. Viability, apoptosis and necrosis were quantified by FACS analysis (propidium iodide/Annexin V staining). Gene expression was analysed by DNA microarrays and the results validated for selected genes by rtPCR. Protein level changes were documented by western blot analysis. Cell proliferation was analysed by BrdU ELISA assay. The single substances TRAIL and TRD significantly induced apoptotic cell death and decreased proliferation in rhabdomyosarcoma and epithelioid cell sarcoma cells. The combined use of TRAIL and TRD resulted in a synergistic apoptotic effect in all three cell lines, especially in rhabdomyosarcoma cells leaving 18% viable cells after 48 h of incubation (p<0.05). Analysis of the differentially regulated genes revealed that TRD and TRAIL influence apoptotic pathways, including the TNF-receptor associated and the mitochondrial pathway. Microarray analysis revealed remarkable expression changes in a variety of genes, which are involved in different apoptotic pathways and cross talk to other pathways at multiple levels. This in vitro study demonstrates that TRAIL and TRD synergise in inducing apoptosis and inhibiting proliferation in different human STS cell lines. Effects on gene expression differ relevantly in the sarcoma entities. These

  8. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

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    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  9. Divergent effects of taurolidine as potential anti-neoplastic agent: inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo.

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    Abramjuk, Claudia; Bueschges, Michael; Schnorr, Jörg; Jung, Klaus; Staack, Andrea; Lein, Michael

    2009-08-01

    We investigated taurolidine (TRD) against various human bladder cell lines and the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in ascending concentrations depending on different incubation times on cell proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested cell lines. Increasing concentrations and longer incubation times decreased the proliferation depending on the primary quantities of cells. For in vivo studies, an orthotopic rat bladder carcinoma was used. The animals were treated intravenously or intravesically and the tumors were harvested and weighted after the study. In contrast to other authors we could not find any anti-proliferative effect, we actually showed that instillation into the rat urinary bladder enhanced tumor growth.

  10. Microbiocidal effects of various taurolidine containing catheter lock solutions

    NARCIS (Netherlands)

    Olthof, E.D.; Nijland, R van; Gulich, A.F.; Wanten, G.J.A.

    2015-01-01

    BACKGROUND & AIMS: We have recently shown that a catheter lock solution containing taurolidine dramatically decreases catheter-related bloodstream infections (CRBSI) in patients on home parenteral nutrition (HPN) when compared to heparin. Since several taurolidine formulations are commercially avail

  11. Taurolidine in Pediatric Home Parenteral Nutrition Patients.

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    Hulshof, Emma Claire; Hanff, Lidwien Marieke; Olieman, Joanne; de Vette, Susanna; Driessen, Gert-Jan; Meeussen, Conny; Escher, Johanna Caroline

    2017-02-01

    To reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients, the use of taurolidine was introduced in the Sophia Children's Hospital in 2011. This introduction led to a reduction in catheter-related bloodstream infections: 12.7/1000 catheter days before the use of taurolidine, compared with 4.3/1000 catheter days afterwards (n = 7) [relative risk = 0.36, 95% confidence interval: 0.20-0.65 (P = 0.018)].

  12. The evolving role of taurolidine in cancer therapy.

    LENUS (Irish Health Repository)

    Neary, Peter M

    2010-04-01

    BACKGROUND AND DESIGN: Taurolidine consists of two taurinamide rings derived from the naturally occurring amino acid taurine. It has been utilized to prevent adhesions, as an antimicrobial, and as an anti-inflammatory agent. More recently, it has been found to exert antineoplastic activity. We reviewed the literature regarding taurolidine and its role in cancer treatment. RESULTS AND CONCLUSION: Taurolidine induces cancer cell death through a variety of mechanisms. Even now, all the antineoplastic pathways it employs are not completely elucidated. It has been shown to enhance apoptosis, inhibit angiogenesis, reduce tumor adherence, downregulate proinflammatory cytokine release, and stimulate anticancer immune regulation following surgical trauma. Apoptosis is activated through both a mitochondrial cytochrome-c-dependent mechanism and an extrinsic direct pathway. A lot of in vitro and animal data support taurolidine\\'s tumoricidal action. Taurolidine has been used as an antimicrobial agent in the clinical setting since the 1970s and thus far appears nontoxic. The nontoxic nature of taurolidine makes it a favorable option compared with current chemotherapeutic regimens. Few published clinical studies exist evaluating the role of taurolidine as a chemotherapeutic agent. The literature lacks a gold-standard level 1 randomized clinical trial to evaluate taurolidine\\'s potential antineoplastic benefits. However, these trials are currently underway. Such randomized control studies are vital to clarify the role of taurolidine in modern cancer treatment.

  13. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    OpenAIRE

    Reyhan Akhtar; Mohd Ali; Safrannisa Mahmood; Sankar Nath Sanyal

    2014-01-01

    Background: Silibinin a flavonoid from milk thistle (Silybum marianum) exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml) for 24, 48 or 72 h showed a progressive decline in cell viability. Res...

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

    Institute of Scientific and Technical Information of China (English)

    Javid Ali; Bashir Ahmad

    2015-01-01

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

  15. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

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    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  16. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

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    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.

  17. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

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    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells.

  18. Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis By-Products

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    Marie-Elise Carbonneau

    2013-03-01

    Full Text Available Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.

  19. Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

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    Jie, Meng; Cheung, Wan Man; Yu, Vivian; Zhou, Yanling; Tong, Pak Ho; Ho, John W S

    2014-01-01

    Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.

  20. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

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    Fatemeh Haji Abbas Tabrizi

    2016-01-01

    Full Text Available Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC 50 value at 72 h (0.1 μg/ml in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder and flavonoids (10.5 ± 2.0 mg/g of dry powder.The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway.

  1. Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cells.

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    Venkateswararao, Eeda; Sharma, Vinay K; Yun, Jieun; Kim, Youngsoo; Jung, Sang-Hun

    2014-07-01

    To investigate the anti-proliferative effect of NF-κB inhibitor, a series of analogs of (E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5a) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Compounds (E)-1-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5e) and (E)-4-(3-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-oxoprop-1-enyl)benzenesulfonamide (5p) showed good NF-κB inhibition as well as potent anti-proliferative activity. SAR studies showed that all the compounds with potent or moderate NF-κB inhibition displayed good anti-proliferative activity. All the analogs (5b-r) maintained a good correlation between their NF-κB inhibition and anti-proliferative activity though the extent is not directly proportional to each other.

  2. New ursane triterpenoids from Salvia urmiensis Bunge: Absolute configuration and anti-proliferative activity.

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    Farimani, Mahdi Moridi; Bahadori, Mir Babak; Koulaei, Sheyda Ahmadi; Salehi, Peyman; Ebrahimi, Samad Nejad; Khavasi, Hamid Reza; Hamburger, Matthias

    2015-10-01

    Two new triterpenoids, urmiensolide B (1) and urmiensic acid (2), with rare carbon skeletons together with three known compounds were isolated from the aerial parts of Salvia urmiensis Bunge, an endemic species of Iran. The structures were established by a combination of 1D and 2D NMR, and HRESIMS, and in the case of 2 and 3, their structures were confirmed by single-crystal X-ray analysis. The absolute configuration of 2 was established by electronic circular dichroism (ECD) spectra. The new compounds were evaluated for their anti-proliferative activities against A549 and MCF-7 human cancer cell lines. Compounds 1 and 2 showed IC50 values of 2.8 and 1.6 μM against MCF-7 cells, respectively.

  3. Antibacterial effect of taurolidine (2%) on established dental plaque biofilm.

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    Arweiler, Nicole Birgit; Auschill, Thorsten Mathias; Sculean, Anton

    2012-04-01

    Preliminary data have suggested that taurolidine may bear promising disinfectant properties for the therapy of bacterial infections. However, at present, the potential antibacterial effect of taurolidine on the supragingival plaque biofilm is unknown. To evaluate the antibacterial effect of taurolidine on the supragingival plaque biofilm using the vital fluorescence technique and to compare it with the effect of NaCl and chlorhexidine (CHX), 18 subjects had to refrain from all mechanical and chemical hygiene measures for 24 h. A voluminous supragingival plaque sample was taken from the buccal surfaces of the lower molars and wiped on an objective slide. The sample was then divided into three equal parts and mounted with one of the three test or control preparations (a) NaCl, (b) taurolidine 2% and (c) CHX 0.2%. After a reaction time of 2 min, the test solutions were sucked of. Subsequently, the plaque biofilm was stained with fluorescence dye and vitality of the plaque flora was evaluated under the fluorescence microscope (VF%). Plaque samples treated with NaCl showed a mean VF of 82.42 ± 6.04%. Taurolidine affected mean VF with 47.57 ± 16.60% significantly (p taurolidine). Taurolidine possesses a significant antibacterial effect on the supragingival plaque biofilm which was, however, not as pronounced as that of CHX.

  4. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

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    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  5. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

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    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  6. Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities.

    Science.gov (United States)

    Liu, Chao; Liao, Zhi-xin; Liu, Shi-jun; Qu, Yan-bo; Wang, Heng-shan

    2014-07-01

    A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC50 values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2-5 exhibited moderate cytotoxic activities for the two cell lines with the IC50 values ranging from 32.1 to 58.2 μM.

  7. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  8. Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships.

    Science.gov (United States)

    Xu, Wen; Li, Ting; Qiu, Jian-Fang; Wu, Shui-Sheng; Huang, Ming-Qing; Lin, Li-Gen; Zhang, Qing-Wen; Chen, Xiu-Ping; Lu, Jin-Jian

    2015-01-01

    This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 μM for 3 and 18.01, 15.97, and 13.56 μM for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.

  9. Chitin and chitosan from the Norway lobster by-products: Antimicrobial and anti-proliferative activities.

    Science.gov (United States)

    Sayari, Nadhem; Sila, Assaâd; Abdelmalek, Baha Eddine; Abdallah, Rihab Ben; Ellouz-Chaabouni, Semia; Bougatef, Ali; Balti, Rafik

    2016-06-01

    Chitin was recovered through enzymatic deproteinization of the Norway lobster (Nephrops norvegicus) processing by-products. The obtained chitin was characterized and converted into chitosan by N-deacetylation, the acid-soluble form of chitin. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR) and 13 Cross polarization magic angle spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy. The antimicrobial activity and anti-proliferative capacity of chitosan were evaluated. Antimicrobial activity assays indicated that prepared chitosan exhibited marked inhibitory activity against the bacterial and fungal strains tested. Further, cytotoxic effects of chitosan samples on human colon carcinoma cells HCT116 was evaluated using the MTT assay. Chitosan showed the antiproliferative capacity against the colon-cancer-cell HCT116 in a dose dependent manner with IC50 of 4.6mg/ml. Indeed, HCT116 cell proliferation was significantly inhibited (p<0.05) between 13.5 and 67.5% at 0.5-6mg/mL of chitosan after 24h of cell treatment. The chitosan showed high antitumor activity which seemed to be dependent on its characteristics such as acetylation degree.

  10. Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract.

    Science.gov (United States)

    Thani, Wasina; Vallisuta, Omboon; Siripong, Pongpan; Ruangwises, Nongluck

    2010-03-01

    In this study the leaves of the Thai noni/Yor, (Morinda citrifolia Linn.) were extracted by several methods and evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as a Vero (African green monkey kidney) cell line, employing the MTT colorimetric method, comparing it to damnacanthal, rutin, and scopoletin. The dichloromethane extract of the fresh leaf showed a better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50 microg/ml, respectively. The dichloromethane extract of dried leaves revealed cytotoxicity against the KB cell line with an IC50 value of 39.00 microg/ml. Other extracts, as well as rutin and scopoletin, showed reduced anti-proliferative effects on all cancer cell lines (IC50 103 to over 600 microg/ml). Interestingly, the damnacanthal had potent cytotoxicity against all cancer cell lines and Vero cell lines. These results suggest Thai noni extracts may be safer than the pure compounds, due to their higher safety ratios, which is a good indicator for possible cancer treatment. Several non-aqueous extracts from the leaves showed antioxidant properties, giving IC50 values of 0.20-0.35 mg/ml. It can be concluded the leaves of M. citrifolia may have benefit as a food supplement for chemoprevention against epidermoid and cervical cancers.

  11. White kidney bean lectin exerts anti-proliferative and apoptotic effects on cancer cells.

    Science.gov (United States)

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2016-04-01

    A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8 μM; HepG2 cells: 19.7 μM; MCF7 cells: 26.9 μM; and WRL68 cells: >80 μM). The activity could be reduced by addition of glucosamine, which occupies the binding sites of WKBL, indicating that carbohydrate binding is crucial for the activity. Annexin V-FITC and PI staining, JC-1 staining and Hoechst 33342 staining revealed that apoptosis was induced on WKBL-treated HONE1 cells and HepG2 cells, but not as obviously on MCF7 cells. Cell cycle analysis also showed a slight cell cycle arrest on HONE1 cells after WKBL treatment. Western blotting suggested that WKBL induced apoptosis of HONE1 cells occurred through the extrinsic apoptosis pathway, with detection of increased level of active caspase 3, 8 and 9.

  12. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-11-06

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it.

  13. Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

    Science.gov (United States)

    Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

    2007-09-25

    The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (pCactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.

  14. The effect of taurolidine on experimental thrombus formation.

    Science.gov (United States)

    Kaptanoglu, Levent; Kucuk, Hasan Fehmi; Colak, Elif; Kurt, Necmi; Bingul, Sadik Mehmet; Akyol, Huseyin; Torlak, Oguzhan Aziz; Yazici, Fatma

    2008-01-14

    Venous thrombosis can be the source of emboli, a significant health risk encountered throughout surgical and medical clinics. Taurolidine is an antimicrobial agent used to prevent intraabdominal adhesion formation and sepsis in experimental and clinical trials. The aim of this study is to evaluate effect of taurolidine on experimental thrombus formation and make a comparison with low-molecular weight heparin. Four groups of ten Wistar-Albino rats (300-350 g) were used; with the first and second groups each being administered 10 and 20 mg of taurolidine, the third group low-molecular weight heparin and the fourth group saline solution (control group) respectively. Experimental thrombus formation was performed in rats in the area of the abdominal inferior vena cava by using a combination of stasis and hypercoagulability described by Wessler et al. [Wessler, S., Reimer, S.M., Sheps, M.C., 1959. Biologic assay of a thrombosis inducing activity in human serum. J. Appl. Physiol. 14:943-946.]. Thrombocyte count, the weight of thrombus, prothrombin time and activated partial thromboplastin time and activities of coagulation factors were measured and compared across groups. Thrombus weights in the taurolidine treated groups were lower than the control group and greater than the low-molecular weight heparin treated group. Taurolidine was found to decrease activities of coagulation factors V, VIII, IX, XI and XII. Taurolidine showed no effect on activated partial thromboplastin time and prothrombin time values; however, it decreased thrombus weight, but not as much as low-molecular weight heparin. The cause of these findings in our study may be related to the minimized effect of taurolidine on factor II, VII, and X activities. These effects likely render the agent ineffective in the prevention of venous thrombosis. Taurolidine was found to be less effective than low-molecular weight heparin in prevention of thrombus formation.

  15. Rational design, synthesis and anti-proliferative evaluation of novel 1,4-benzoxazine-[1,2,3]triazole hybrids.

    Science.gov (United States)

    Bollu, Rajitha; Palem, Jyothsna Devi; Bantu, Rajashaker; Guguloth, Vijayacharan; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, Nishant

    2015-01-07

    A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI50 values ranging from 1.2 to 2.5 μM and 0.1-1.1 μM respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 5l showed significant activity against MDA-MB-231 and IMR32 with GI50 values ranging from 1.1 and 1.4 μM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids.

  16. Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

    Directory of Open Access Journals (Sweden)

    Jan Tauchen

    Full Text Available ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively, while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively. However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively. Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

  17. Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

    Directory of Open Access Journals (Sweden)

    Samira Samane

    2006-01-01

    Full Text Available Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2, ERK kinase (MEK1/2 and protein kinase B (PKB/Akt signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  18. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    Science.gov (United States)

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  19. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    Science.gov (United States)

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.

  20. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tao; Meng, Lingjun [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States); Tsai, Robert Y.L., E-mail: rtsai@ibt.tamhsc.edu [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States)

    2011-10-22

    Highlights: {yields} Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. {yields} Cell type-dependent synergy between MPA and anti-proliferative agents. {yields} The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. {yields} The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  1. Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

    Science.gov (United States)

    Akef, Hassan; Kotb, Nahla; Abo-Elmatty, Dina; Salem, Sayed

    2017-01-01

    The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells. PMID:28382285

  2. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships.

    Science.gov (United States)

    Gnabre, John; Unlu, Irem; Chang, Tso-Cheng; Lisseck, Paul; Bourne, Bryan; Scolnik, Ryan; Jacobsen, Neil E; Bates, Robert; Huang, Ru Chih

    2010-10-15

    Separate benzocyclooctadiene lignans were isolated from the berries of Schisandra chinensis in milligram quantities on analytical reverse phase (RP) HPLC by an automated repeat-injection method and shown to have anti-proliferative activity against human colorectal cancer cells. Structures of the compounds were determined by a combination of NMR and mass spectrometry. Stereospecific NMR assignments for gomisin-N and deoxyschisandrin, gave more complete and accurate data than previously reported, based on 600MHz 2D HSQC, DQF-COSY and HMBC data. Comparison of coupling constants and HMBC crosspeak intensities with calculated and X-ray crystal structures confirmed their stereochemistry and conformation. Analysis of structure-activity relationships revealed the importance of key structural determinants. The S-biphenyl configuration of gomisin N, the most active lignan, correlated with increased anti-proliferative activity, while the presence of a hydroxyl group at the C7 position reduced or abolished this activity. Increased activity was also observed when a methylenedioxy group was present between C12 and C13. The percent yield of the most active compounds relative to the starting plant materials was 0.0156% for deoxyschisandrin and 0.0173% for gomisin N. The results of these studies indicate that automated repeat-injection method of analytical HPLC may provide a superior alternative to the standard semi-preparative HPLC techniques for separation of complex mixtures.

  3. Absence of microbial adaptation to taurolidine in patients on home parenteral nutrition who develop catheter related bloodstream infections and use taurolidine locks

    NARCIS (Netherlands)

    Olthof, E.D.; Rentenaar, R.J.; Rijs, A.J.M.M.; Wanten, G.J.A.

    2013-01-01

    BACKGROUND & AIMS: Some home parenteral nutrition (HPN) patients develop catheter related bloodstream infections (CRBSI) despite using an anti-microbial catheter lock solution taurolidine. The aim of this study was to assess whether long-term use of taurolidine leads to selective growth of microorga

  4. Furanodiene presents synergistic anti-proliferative activity with paclitaxel via altering cell cycle and integrin signaling in 95-D lung cancer cells.

    Science.gov (United States)

    Xu, Wen-Shan; Dang, Yuan-Ye; Chen, Xiu-Ping; Lu, Jin-Jian; Wang, Yi-Tao

    2014-02-01

    Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Recently, we found that the combined treatment of FUR with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D lung cancer cells. Herein, we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase. The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down-regulated in the group of combined treatment. The dramatically down-regulated expression of integrin β4, focal adhesion kinase and paxillin might partially contribute to the synergic effect. Though FUR alone obviously induced endoplasmic reticulum stress, this signaling pathway may not contribute to the synergetic anti-proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group.

  5. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  6. Chemical Composition, Antioxidant, Anti-Inflammatory and Anti-Proliferative Activities of Essential Oils of Plants from Burkina Faso

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A.; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography–mass spectrometry and gas chromatography–flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  7. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Bagora Bayala

    Full Text Available This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78% and β-caryophyllene (10.54% for Ocimum basilicum; 1, 8-cineol (31.22%, camphor (12.730%, α-pinene (6.87% and trans α-bergamotene (5.32% for Ocimum americanum; β-caryophyllene (21%, α-pinene (20.11%, sabinene (10.26%, β-pinene (9.22% and α-phellandrene (7.03% for Hyptis spicigera; p-cymene (25.27%, β-caryophyllene (12.70%, thymol (11.88, γ-terpinene (9.17% and thymyle acetate (7.64% for Lippia multiflora; precocene (82.10%for Ageratum conyzoides; eucalyptol (59.55%, α-pinene (9.17% and limonene (8.76% for Eucalyptus camaldulensis; arcurcumene (16.67%, camphene (12.70%, zingiberene (8.40%, β-bisabolene (7.83% and β-sesquiphellandrène (5.34% for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the

  8. Mitogenic and anti-proliferative activity of a lectin from the tubers of Voodoo lily (Sauromatum venosum).

    Science.gov (United States)

    Singh Bains, Jagmohan; Singh, Jatinder; Kamboj, Sukhdev Singh; Nijjar, Kamaljeet Kaur; Agrewala, Javed N; Kumar, Vinod; Kumar, Ashok; Saxena, A K

    2005-05-25

    A new lectin with the potent mitogenic and in vitro anti-proliferative activity was isolated from the tubers of a wild monocotyledonous plant Sauromatum venosum (Schott), from the family Araceae, by affinity chromatography on the asialofetuin linked amino-activated silica beads. The apparent native molecular mass of S. venosum lectin (SVL), as determined by gel filtration chromatography, was 54 kDa. In HPLC, size exclusion and cation exchange chromatography, SVL gave a single peak and also a single band of 13.5 kDa in SDS-PAGE, pH 8.3, under reducing and non-reducing conditions, indicating that the lectin is composed of four identical subunits. S. venosum lectin agglutinated rabbit, rat, sheep and guinea pig erythrocytes but reacted with goat erythrocytes after the neuraminidase treatment. However, SVL was unable to agglutinate human ABO blood group erythrocytes even after treatment with neuraminidase. SVL was inhibited by N-acetyl-D-Lactosamine (LacNAc), which is an important marker in various carcinomas and a complex desialylated glycoprotein, asialofetuin. The amino acid composition showed that lectin contained a high amount of aspartic acid and glycine but totally devoid of cysteine. However, trace amounts of methionine was present. The lectin showed a potent mitogenic response towards BALB/c splenocytes and human lymphocytes. As the mitogenic stimulation was more than that of Con A, a standard well-known plant mitogen and the response of this lectin was almost double than that of Con A. This lectin is endowed with proliferation of T cells as revealed by IL-2 bioassay but showed no production of immunoglobulins thus indicating the non-stimulation of B cells. SVL significantly inhibited the proliferation of murine cancer cell-lines, i.e., WEHI-279 to 84.6%, J774 to 81%, P388D1 to 74% and A-20 to 47%. In addition, the in vitro anti-proliferative activity of SVL was also evaluated against nine human cancer cell lines representing different organs and tissues

  9. The pharmacokinetics of taurolidine metabolites in healthy volunteers.

    Science.gov (United States)

    Gong, Li; Greenberg, Howard E; Perhach, James L; Waldman, Scott A; Kraft, Walter K

    2007-06-01

    Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the end of infusion for taurinamide, whereas that of taurultam was reached before completion of infusion. The taurolidine metabolite taurultam demonstrated a shorter half-life and lower systemic exposure than taurinamide. Shortening of infusion duration increased the C(max) and AUC of taurultam. Changes in infusion rate did not substantially change the pharmacokinetic parameters of taurinamide.

  10. Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines.

    Science.gov (United States)

    Walters, Denise K; Muff, Roman; Langsam, Bettina; Gruber, Philipp; Born, Walter; Fuchs, Bruno

    2007-08-01

    Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent.

  11. Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.

    Science.gov (United States)

    Lobb, Karen L; Hipskind, Philip A; Aikins, James A; Alvarez, Enrique; Cheung, Yiu-Yin; Considine, Eileen L; De Dios, Alfonso; Durst, Gregory L; Ferritto, Rafael; Grossman, Cora Sue; Giera, Deborah D; Hollister, Beth A; Huang, Zhongping; Iversen, Philip W; Law, Kevin L; Li, Tiechao; Lin, Ho-Shen; Lopez, Beatriz; Lopez, Jose E; Cabrejas, Luisa M Martin; McCann, Denis J; Molero, Victoriano; Reilly, John E; Richett, Michael E; Shih, Chuan; Teicher, Beverly; Wikel, James H; White, Wesley T; Mader, Mary M

    2004-10-21

    Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds.

  12. Potential Anti-proliferative and Immunomodulatory Effects of Marine Microalgal Exopolysaccharide on Various Human Cancer Cells and Lymphocytes In Vitro.

    Science.gov (United States)

    Park, Geon-Tae; Go, Ryeo-Eun; Lee, Hae-Miru; Lee, Geum-A; Kim, Cho-Won; Seo, Jeong-Woo; Hong, Won-Kyung; Choi, Kyung-Chul; Hwang, Kyung-A

    2017-02-04

    Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment. Alterations in immunoreactivity by the microalgal EPS were examined by measuring its influence on the growth of T and B lymphocytes and cytokine production of T cells. In cell viability assay, the microalgal EPS inhibited cancer cell growth at the lowest concentration of 10(-11) dilution and in a dose-responsive manner within the range of dilution of 10(-11)~10(-3). In addition, the protein expression of cell cycle progression genes such as cyclin D1 and E in these cancer cell lines was significantly reduced by the microalgal EPS in a dose- and a time-dependant manner. In cell proliferation assay using T and B cells, the microalgal EPS induced B cell proliferation even at the lowest dilution of 10(-11), but not T cells. In cytokine assay, the microalgal EPS decreased the formation of IL-6 and INF-γ at 10(-3) dilution compared to the control and had no significant effects on TNF-α. Collectively, these findings suggest that the EPS derived from microalgae Thraustochytriidae sp. GA has an anti-proliferative activity against cancer cells and an immunomodulatory effect by having an influence on B cell proliferation and cytokine secretion of T cells.

  13. Probing the GnRH receptor agonist binding site identifies methylated triptorelin as a new anti-proliferative agent

    Directory of Open Access Journals (Sweden)

    Robert P Millar

    2012-06-01

    Full Text Available D-amino acid substitutions at Glycine postion-6 in GnRH-I decapeptide can possess super-agonist activity and enhanced in vivo pharmacokinetics. Agonists elicit growth-inhibition in tumorigenic cells expressing the GnRH receptor above threshold levels. However, new agonists with modified properties are required to improve the anti-proliferative range. Effects of residue substitutions and methylations on tumourigenic HEK293[SCL60] and WPE-1-NB26-3 prostate cells expressing the rat GnRH receptor were compared. Peptides were ranked according to receptor binding affinity, induction of inositol phosphate production and cell growth-inhibition. Analogues possessing D-Trp6 (including Triptorelin, D-Leu6 (including Leuprolide, D-Ala6, D-Lys6, or D-Arg6 exhibited agonist and anti-proliferative activity. Residues His5 or His5,Trp7,Tyr8, corresponding to residues found in GnRH-II , were tolerated, with retention of sub-nanomolar/low nanomolar binding affinities and EC50s for receptor activation and IC50s for cell growth-inhibition. His5D-Arg6-GnRH-I exhibited reduced binding affinity and potency, effective in the mid-nanomolar range. However, all GnRH-II-like analogues were less potent than Triptorelin. By comparison, three methylated-Trp6 Triptorelin variants showed differential binding, receptor activation and anti-proliferation potency. Significantly, 5-Methyl-DL-Trp6-Triptorelin was equipotent to triptorelin. Subsequent studies should determine whether pharmacologically enhanced derivatives of Triptorelin can be developed by further alkylations, without substitutions or cleavable cytotoxic adducts, to improve the extent of growth-inhibition of tumour cells expressing the GnRH receptor.

  14. Taurolidine and povidone-iodine induce different types of cell death in malignant pleural mesothelioma.

    Science.gov (United States)

    Opitz, I; Sigrist, B; Hillinger, S; Lardinois, D; Stahel, R; Weder, W; Hopkins-Donaldson, S

    2007-06-01

    Taurolidine and povidone-iodine (PVP-I) are used in every day clinical practice, taurolidine as a broad spectrum antibiotic, and PVP-I as an antiseptic. The type of cell death induced in malignant pleural mesothelioma (MPM) cell lines by these agents was compared, and their ability to sensitize to chemotherapy assessed. Both taurolidine and PVP-I inhibited MPM cell growth after 7.5min incubation, but taurolidine was more effective at later time points and was more specific towards tumour cells than PVP-I. Taurolidine induced death by caspase-dependent and independent mechanisms, whereas in contrast, PVP-I induced a necrotic phenotype that was not caspase-dependent. Interestingly, both taurolidine and PVP-I induced the production of reactive oxygen intermediates and decreased mitochondrial membrane permeability, and cell death was inhibited by the oxygen scavenger N-acetyl cysteine. Taurolidine but not PVP-I treatment resulted in p53 activation in 2/3 MPM cell lines and a decrease in the protein levels of survivin, Bcl-2 and Mcl-1. Survivin also decreased in response to PVP-I whereas Bcl-xL remained unaffected by both treatments. Targeting of Bcl-xL with siRNA sensitized MPM cells to taurolidine and taurolidine treatment sensitized MPM cells to cisplatin-induced apoptosis. In conclusion, taurolidine and PVP-I are both cytotoxic to human MPM cells at early and late time points and induce reactive oxygen intermediate production. Taurolidine induces apoptosis and necrosis, activates p53 and sensitizes cells to cisplatin, whereas PVP-I inhibits cell growth via necrosis. Both agents are promising candidates for use in local treatment within multimodality concepts for MPM.

  15. Chemical composition, and anti-proliferative and anti-inflammatory effects of the leaf and wholeplant samples of diploid and tetraploid gynostemma pentaphyllum

    Science.gov (United States)

    Leaf and whole-plant samples of the diploid and tetraploid Gynostemma pentaphyllum (GP)were investigated and compared for their chemical compositions, and their potential anti-proliferative and anti-inflammatory effects. The highest levels of total flavonoids and phenolics were observed in the diplo...

  16. Efficacy of taurolidine against periodontopathic species--an in vitro study.

    Science.gov (United States)

    Eick, Sigrun; Radakovic, Sabrina; Pfister, Wolfgang; Nietzsche, Sandor; Sculean, Anton

    2012-06-01

    The antimicrobial effect of taurolidine was tested against periodontopathic species in comparison to chlorhexidine digluconate in the presence or absence of serum. Minimal inhibitory concentrations (MIC), microbiocidal concentrations (MBC), as well as killing were determined against 32 different microbial strains including 3 Porphyromonas gingivalis, 3 Aggregatibacter actinomycetemcomitans, and 15 potentially superinfecting species with and without 25% v/v human serum. The MIC(50) of taurolidine against the tested microbial strains was 0.025% and the MIC(90) 0.05%. The respective values for the MBCs were 0.05% and 0.1%. Addition of 25% serum (heat-inactivated) did not change the MIC and MBC values of taurolidine. In contrast, MICs and MBCs of chlorhexidine (CHX) increased by two steps after addition of serum. Taurolidine killed microorganisms in a concentration and time-dependent manner, the killing rate of 1.6% taurolidine was 99.08% ± 2.27% in mean after 2 h. Again, killing activity of taurolidine was not affected if serum was added, whereas addition of inactivated serum clearly reduced the killing rate of all selected bacterial strains by CHX. Therefore, taurolidine possesses antimicrobial properties which are not reduced in the presence of serum as a main component in gingival crevicular fluid and wound fluid. Taurolidine may have potential as an antimicrobial agent in non-surgical and surgical periodontal treatment.

  17. Taurolidine-Fibrin-Sealant-Matrix using spray application for local treatment of brain tumors.

    Science.gov (United States)

    Stendel, Ruediger; Scheurer, Louis; Schlatterer, Kathrin; Gminski, Richard; Möhler, Hanns

    2004-01-01

    Malignant gliomas tend to recur in the vast majority of cases. Recurrent gliomas may arise from vital tumor cells present in this zone around the resection margin. It appears promising to combine tumor resection with local chemotherapy using an antineoplastic, but non-toxic agent. Taurolidine exerts a selective antineoplastic effect by induction of programmed cell death and has anti-angiogenic activity. Fibrin sealant is completely degradable and firmly adheres to brain tissue, suggesting that it would provide a suitable matrix for taurolidine delivery--a Taurolidine-Fibrin-Sealant-Matrix (TFM)--in the local treatment of brain tumors. The potential of local delivery of taurolidine out of a fibrin sealant matrix was investigated. Taurolidine could be suspended homogeneously in both the thrombin and the procoagulant protein components of the fibrin sealant. The fibrin sealant matrix was a suitable carrier for the suspension of taurolidine at a concentration that ensured the release of therapeutically effective amounts of the drug over a period of 2 weeks in vitro. The antineoplastic action of taurolidine was not affected by embedding in the fibrin sealant matrix. The described drug delivery system may be suitable for local taurolidine treatment of brain tumors following complete or partial resection or of tumors that are non-resectable because of their location.

  18. The tumor-suppressive reagent taurolidine is an inhibitor of protein biosynthesis.

    Science.gov (United States)

    Braumann, Chris; Henke, Wolfgang; Jacobi, Christoph A; Dubiel, Wolfgang

    2004-11-01

    Taurolidine has been successfully used as a disinfectant and to prevent the spreading and growth of tumor cells after surgical excision. However, the underlying mechanisms regarding its effects remain obscure. Here, we show that taurolidine treatment reduces endogenous levels of IkappaBalpha, p105, c-Jun, p53 and p27 in a dose-dependent manner in colon adenocarcinoma cells, which can be in part due to massive cell death. Because expression of tested proteins was affected by taurolidine, its influence on protein expression was studied. In the coupled transcription/translation system, taurolidine inhibited c-Jun expression with an IC50 value of 1.4 mM. There was no or little effect on transcription. In contrast, translation of c-Jun or p53 mRNA was completely inhibited by taurolidine. To determine which step of translation was affected, prominent complexes occurring in the course of translation were analyzed by density gradient centrifugation. In the presence of taurolidine, no preinitiation translation complex was assembled. Taurolidine also suppressed protein expression in bacteria. Based on our data, we conclude that taurolidine blocks a fundamental early phase of translation, which might explain its effects as a disinfectant and inhibitor of tumor growth.

  19. In-vitro activity of taurolidine on single species and a multispecies population associated with periodontitis.

    Science.gov (United States)

    Zollinger, Lilly; Schnyder, Simone; Nietzsche, Sandor; Sculean, Anton; Eick, Sigrun

    2015-04-01

    The antimicrobial activity of taurolidine was compared with minocycline against microbial species associated with periodontitis (four single strains and a 12-species mixture). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs), killing as well as activities on established and forming single-species biofilms and a 12-species biofilm were determined. The MICs of taurolidine against single species were always 0.31 mg/ml, the MBCs were 0.64 mg/ml. The used mixed microbiota was less sensitive to taurolidine, MIC and the MBC was 2.5 mg/ml. The strains and the mixture were completely killed by 2.5 mg/ml taurolidine, whereas 256 μg/ml minocycline reduced the bacterial counts of the mixture by 5 log10 colony forming units (cfu). Coating the surface with 10 mg/ml taurolidine or 256 μg/ml minocycline prevented completely biofilm formation of Porphyromonas gingivalis ATCC 33277 but not of Aggregatibacter actinomycetemcomitans Y4 and the mixture. On 4.5 d old biofilms, taurolidine acted concentration dependent with a reduction by 5 log10 cfu (P. gingivalis ATCC 33277) and 7 log10 cfu (A. actinomycetemcomitans Y4) when applying 10 mg/ml. Minocycline decreased the cfu counts by 1-2 log10 cfu independent of the used concentration. The reduction of the cfu counts in the 4.5 d old multi-species biofilms was about 3 log10 cfu after application of any minocycline concentration and after using 10 mg/ml taurolidine. Taurolidine is active against species associated with periodontitis, even within biofilms. Nevertheless a complete elimination of complex biofilms by taurolidine seems to be impossible and underlines the importance of a mechanical removal of biofilms prior to application of taurolidine.

  20. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    Science.gov (United States)

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

  1. Biosynthesis of Anti-Proliferative Gold Nanoparticles Using Endophytic Fusarium oxysporum Strain Isolated from Neem (A. indica) Leaves.

    Science.gov (United States)

    Siddiqui, Ejaz Ahmad; Ahmad, Absar; Julius, Anju; Syed, Asad; Khan, Shadab; Kharat, Mahesh; Pai, Kalpana; Kadoo, Narendra; Gupta, Vidya

    2016-01-01

    Here we report a simple, rapid, environment friendly approach for the synthesis of gold nanoparticles using neem (Azadirachta indica A. Juss.) fungal endophyte, which based upon morphological and cultural characteristics was eventually identified as Fusarium oxysporum. The aqueous precursor (HAuCl4) solution when reacted with endophytic fungus resulted in the biosynthesis of abundant amounts of well dispersed gold nanoparticles of 10-40 nm with an average size of 22nm. These biosynthesized gold nanoparticles were then characterized by standard analytical techniques such as UV-Visible spectroscopy, X-ray diffraction, Transmission Electron Microscopy and Fourier Transform Infrared Spectroscopy. Cytotoxic activity of these nanoparticles was checked against three different cell types including breast cancer (ZR-75-1), Daudi (Human Burkitt's lymphoma cancer) and normal human peripheral blood mononuclear cells (PBMC), where it was found that our gold nanoparticles are anti-proliferative against cancer cells but completely safe toward normal cells. In addition to this, assessment of toxicity toward human RBC revealed less than 0.1 % hemolysis as compared to Triton X-100 suggesting safe nature of our biosynthesized gold nanoparticles on human cells. Also, our nanoparticles exhibited no anti-fungal (against Aspergillus niger) or anti-bacterial [against Gram positive (Bacillus subtilis & Staphylococcus aureus) and Gram negative (Escherichia coli & Pseudomonas aeruginosa) bacteria] activity thus suggesting their non-toxic, biocompatible nature. The present investigation opens up avenues for ecofriendly, biocompatible nanomaterials to be used in a wide variety of application such as drug delivery, therapeutics, theranostics and so on.

  2. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  3. A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.

    Directory of Open Access Journals (Sweden)

    Elena Bausch

    Full Text Available Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent.

  4. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.

    Science.gov (United States)

    Kontogianni, Vassiliki G; Tomic, Goran; Nikolic, Ivana; Nerantzaki, Alexandra A; Sayyad, Nisar; Stosic-Grujicic, Stanislava; Stojanovic, Ivana; Gerothanassis, Ioannis P; Tzakos, Andreas G

    2013-01-01

    The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS(n)). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-α release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile.

  5. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines.

    Science.gov (United States)

    Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

    2014-03-01

    Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0 /G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0 /G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer.

  6. Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action.

    Science.gov (United States)

    Liu, Wei; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

    2011-01-01

    Population studies suggest putative links between vitamin D (VD)-deficiency and risk of cancer and diabetes. The insulin/IGF-I receptor represents a signaling target of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) that is implicated in both diabetes and cancer, therefore we hypothesized that VD actions may be mediated through this adhesion molecule. In this study, we show that 1,25 vitamin D3 and its analogues EB1089 and KH1060 potently inhibit CEACAM1 expression in cancer cells. This effect was associated with significant reductions in mRNA and protein levels, resulting from transcriptional and posttranslational actions respectively. Insulin/IGF-I-mediated IRS-1 and Akt activation were enhanced by VD treatment. Similarly, CEACAM1 downregulation significantly upregulated the insulin and IGF-I receptors and mimicked the effect of VD-mediated enhanced insulin/IGF-I receptor signaling. Despite improved insulin/IGF-I signaling, the anti-proliferative actions of VD were preserved in the absence or presence of forced CEACAM1 expression. Forced CEACAM1, however, abrogated the anti-invasive actions of VD. Our findings highlight CEACAM1 as a target of VD action. The resulting inhibition of CEACAM1 has potentially beneficial effects on metabolic disorders without necessarily compromising the anticancer properties of this vitamin.

  7. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

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    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  8. Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

    Science.gov (United States)

    Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

    2016-01-01

    To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

  9. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

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    Justyna Moskwa

    Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  10. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules.

  11. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells

    Directory of Open Access Journals (Sweden)

    Neo Soek-Ying

    2011-01-01

    Full Text Available Abstract Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells. Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography/mass spectrometry (UHPLC-MS analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay. Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2 than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.

  12. The calcium channel blocker amlodipine exerts its anti-proliferative action via p21(Waf1/Cip1) gene activation.

    Science.gov (United States)

    Ziesche, Rolf; Petkov, Ventzislav; Lambers, Christopher; Erne, Paul; Block, Lutz-Henning

    2004-10-01

    Proliferation of vascular smooth muscle cells (VSMC) contributes to the progression of atherosclerotic plaques. Calcium channel blockers have been shown to reduce VSMC proliferation, but the underlying molecular mechanism remains unclear. p21(Waf1/Cip1) is a potent inhibitor of cell cycle progression. Here, we demonstrate that amlodipine (10(-6) to 10(-8) M) activates de novo synthesis of p21(Waf1/Cip1) in vitro. We show that amlodipine-dependent activation of p21(Waf1/Cip1) involves the action of the glucocorticoid receptor (GR) and C/EBP-alpha. The underlying pathway apparently involves the action of mitogen-activated protein kinase or protein kinase C, but not of extracellular signal-related kinase or changes of intracellular calcium. Amlodipine-induced p21(Waf1/Cip1) promoter activity and expression were abrogated by C/EBP-alpha antisense oligonucleotide or by the GR antagonist RU486. Amlodipine-dependent inhibition of cell proliferation was partially reversed by RU486 at 10(-8) M (58%+/-29%), antisense oligonucleotides targeting C/EBP-alpha (91%+/-26%), or antisense mRNAs targeting p21(Waf1/Cip1) (96%+/-32%, n=6); scrambled antisense oligonucleotides or those directed against C/EBP-beta were ineffective. The data suggest that the anti-proliferative action of amlodipine is achieved by induction of the p21 (Waf1/Cip1) gene, which may explain beneficial covert effects of this widely used cardiovascular therapeutic drug beyond a more limited role as a vascular relaxant.

  13. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  14. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  15. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

    Science.gov (United States)

    Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

    2016-01-01

    The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

  16. Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines.

    Science.gov (United States)

    Yunos, Nurhanan M; Mutalip, Siti S M; Jauri, Muhammad H; Yu, Jun Q; Huq, Fazlul

    2013-10-01

    Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm) and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose activity was lower in the resistant A2780(cisR) cell line than in the parent A2780 cell line, Andro was found to be three times more active in the A2780(cisR) cell line as compared to that in A2780 cell line. Synergism was observed when Cis and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage of apoptotic cell death was found to be greater for the 0/4 h combination of Andro and Cis as compared to those values from single-drug treatments. The results may be clinically significant if confirmed in vivo.

  17. Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

    OpenAIRE

    Marley, Kevin; Stuart C. Helfand; Simpson, Jennifer; Mata, John E.; Tracewell, William G; Brownlee, Lisa; Bracha, Shay; Séguin, Bernard

    2013-01-01

    Background Osteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteos...

  18. The effect of Taurolidine on adherent and floating subpopulations of melanoma cells.

    Science.gov (United States)

    Shrayer, D P; Lukoff, H; King, T; Calabresi, P

    2003-04-01

    The annual incidence of malignant melanoma is estimated at 10-12 per 100000 inhabitants in countries of Central Europe and the US, with more recent estimates showing a dramatic upward trend. Taurolidine (Carter/Wallace, Cranberry, NJ) is a novel, potentially effective, antitumor chemotherapeutic agent. We hypothesized that Taurolidine could inhibit the growth, induce apoptosis, affect the cell cycle and change morphology of melanoma cells. We expected this process to be different in adherent and floating subpopulations that may be reflective of solid tumors and their metastases. Analysis of MNT-1 human and B16F10 murine melanoma cells showed that at 72 h the IC(50) of Taurolidine was 25.4+/-3.3 microM for MNT-1 human melanoma cells and 30.9+/-3.6 microM for B16F10 murine melanoma cells. Taurolidine induced DNA fragmentation of melanoma cells in a dose-dependent manner. Taurolidine (75 and 100 microM) induced 52-97% Annexin-V binding (apoptosis), respectively. Evaluation of cell cycle after 72 h exposure to Taurolidine (0-100 microM) revealed that the percentage of melanoma cells in S phase increased from 27 to 40% in the adherent subpopulation and from 33 to 49% in the floating subpopulation. Phase contrast microscopy revealed a marked swelling of melanoma cells and decreasing cell numbers in adherent subpopulation starting at 24 h with 25 microM Taurolidine. Shrinkage of cells dominated at 75-100 microM Taurolidine. Using Cytospin assay in the floating population, we observed swelling of melanoma cells induced by 25-100 micro Taurolidine and appearance of giant (multinuclear) forms resulting from exposure to 75-100 micro Taurolidine. Some floating cells with normal morphology were observed with low concentrations of Taurolidine (0-25 microM). These data show that effects of Taurolidine may be different in adherent and floating subpopulations of melanoma cells. More importantly, floating subpopulations that may contain some viable melanoma cells, may be reflective

  19. Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

    Science.gov (United States)

    Wu, Feifei; Zhou, Li; Jin, Wangdong; Yang, Weiji; Wang, Ying; Yan, Bo; Du, Wenlin; Zhang, Qiang; Zhang, Lei; Guo, Yonghua; Zhang, Jin; Shan, Letian; Efferth, Thomas

    2016-01-01

    With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent) pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP) and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X). Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II) inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of A549 cells

  20. Anti-proliferative and apoptosis-inducing effect of theabrownin against non-small cell lung adenocarcinoma A549 cells

    Directory of Open Access Journals (Sweden)

    Feifei Wu

    2016-12-01

    Full Text Available With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC, is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549 cells, using MTT assay, morphological observation (DAPI staining, in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay, and annexin V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X. Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of

  1. [In vitro effect of taurolidine on squamous cell carcinoma in the oral cavity].

    Science.gov (United States)

    Petrovic, L; Schlegel, K A; Ries, J; Park, J; Diebel, E; Schultze-Mosgau, S; Wiltfang, J

    2003-03-01

    Taurolidine (Taurolin) is a derivative of the amino acid taurine, successfully used in the treatment of peritonitis. In vitro and in vivo studies have shown that taurolidine inhibits cell proliferation and induces apoptosis in a variety of tumor cell lines. At present there are no published studies on the use of taurolidine in the treatment of squamous cell carcinoma. Our aim was to examine the inhibition of cell proliferation and induction of apoptosis in cell lines SCC 4 and SCC 15 treated with taurolidine in concentrations of 0.01%, 0.1%, and 0.5%. Analogue to the present investigations on adenocarcinoma cell lines, we used toxic antiseptic povidone iodine in the same concentration as for the reference group. Untreated cells were used as a control group. The cells were incubated with taurolidine or povidone iodine once for 2 h at 37 degrees C in 5% CO(2). Cell proliferation was assessed using WST-1 labeling kit after 3, 24, 48, 72, and 96 h. The additional measurement of cell apoptosis was examined using ELISA(PLUS) cell death detection kit and performed after 0, 24, and 48 h. The findings showed a significant inhibition of cell proliferation and induction of apoptosis in taurolidine-treated cells SCC 4 and SCC 15 in contrast to the reference group treated with povidone iodine or the untreated control group.

  2. In vitro anti-proliferative, anti-bacterial potential and induction of DNA strand break of partially purified Cuscuta reflexa Roxb.

    Directory of Open Access Journals (Sweden)

    Madhulika Bhagat

    2011-01-01

    Full Text Available Cuscuta reflexa is an important medicinal plant, mentioned in Ayurveda, an ancient Indian system of medicine. The plant is selected to evaluate the possibility for novel pharmaceuticals for anticancer and antibiotics drugs. Since most of these drugs had developed resisitance against currently used chemotherapeutics. This study describes the in vitro anti-proliferative, anti-bacterial and single stand DNA break of the holoprasitic plant Cuscuta reflexa. Bioassay-guided fractionation and partial purification of the plant were done and evaluated for antiproliferative activity against human cancer cell lines by SRB assay and single strand DNA break by comet assay. Further antibacterial activity was also performed by agar well diffusion assay. The alcoholic extract, chloroform fraction and partially purified ethylacetate-methanol (1:1 sub-fraction of C. reflexa showed anti-proliferative potential against IMR-32 and 502713 human cancer cell lines. Alcoholic extract exhibited anti-proliferative activity of 74% and 72%, chloroform fraction demonstrated 91% and 95% against neuroblastoma (IMR-32 and colon (502713 cancer cell lines at 100 μg/ml. Single strand DNA break of the chloroform fraction was also demonstrated using comet assay, indicating that possible mode of cell death may be apoptosis. Anti-microbial properties were evaluated against eight species of pathogenic and non-pathogenic microorganisms and maximum zone of inhibition for anti-bacterial activity was found against Staphylococcus aureus (22 mm by alcoholic extract, 21 mm by chloroform fraction and 12 mm by ethylacetate-methanol (1:1 sub-fraction. Minimum inhibitory concentration (MIC of the chloroform fraction was 1500 μg/ml for S. aureus. The plant was found to be equally effective against gram-positive and negative bacteria. Studies are well underway to isolate and identify active compounds from chloroform fraction and ethyl acetate:methanol (1:1 sub-fraction, which can be used as

  3. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

    Directory of Open Access Journals (Sweden)

    Marley Kevin

    2013-01-01

    Full Text Available Abstract Background Osteosarcoma (OS affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Results Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS. Conclusion Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

  4. Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line.

    Science.gov (United States)

    Cortés-Benítez, Francisco; Cabeza, Marisa; Ramírez-Apan, María Teresa; Alvarez-Manrique, Berenice; Bratoeff, Eugene

    2016-10-04

    In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one and evaluated against the androgen-sensitive human prostate adenocarcinoma LNCaP cell line. The cancerous cells were exposed to 50 μM of each compound and the proliferating agent testosterone (T) or dihydrotestosterone (DHT). The most potent compounds from this assay were further tested against the androgen-insensitive PC3 cell line. We also demonstrate the activity of these compounds on rat peripheral blood mononuclear cells for comparison. Both 17β-N-[3,5-bis(trifluoromethyl)phenylcarbamoyl]androst-4-ene-3-one (6f) and 17β-N-(1,3-thiazol-2-ylcarbamoyl)androst-4-ene-3-one (6g) exhibited a higher growth inhibitory effect than commercially available drugs finasteride, flutamide and ketoconazole on LNCaP cells in the presence and absence of androgens. In addition, 6f and 6g demonstrated high potency on PC3 cells suggesting an androgen-independent anti-proliferative effect. Moreover, the novel compounds showed a small effect on rat mononuclear cells, an indication of low toxicity.

  5. Synthesis and evaluation of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties as new potential anti proliferative agents.

    Science.gov (United States)

    Yadagiri, Bandi; Gurrala, Srikanth; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Srujana, Garimella; Jain, Nishant

    2015-01-01

    As an aspect of our ongoing research in search of new anti proliferative agents, a series of novel analogs of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties were synthesized in excellent yields (82-93%). All the newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, ESI/LC-MS, HRMS and evaluated for their in vitro anti proliferative activity against four human cancer cell lines (cervical, breast, pancreatic and alveolar). Among the synthesized compounds, 4b, 6a, 7d and 7l showed potent anti proliferative activity with GI50 values range of 0.079-0.957μM against four human cancer cell lines. However, it was revealed that the compound 7d have shown very close GI50 value 0.079μM as compared with positive control of colchicine against cervical cancer cell line.

  6. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

    Energy Technology Data Exchange (ETDEWEB)

    Min, Kyung-Won [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Zhang, Xiaobo [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100 (China); Imchen, Temjenmongla [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Baek, Seung Joon, E-mail: sbaek2@utk.edu [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

    2012-09-01

    MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

  7. Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities

    Science.gov (United States)

    El-Faham, Ayman; Soliman, Saied M.; Ghabbour, Hazem A.; Elnakady, Yasser A.; Mohaya, Talal A.; Siddiqui, Mohammed R. H.; Albericio, Fernando

    2016-12-01

    Novel series of s-triazine-Schiff base derivatives were synthesized employing ultrasonic irradiation and characterized by NMR (1H and 13C), FT-IR, and elemental analysis. The use of ultrasonic irradiation has allowed the preparation of the target products with better yields in shorter reaction time and excellent purities compared to the conventional heating. X-ray single crystal diffraction experiments verified the molecular structure of four from the new prepared s-triaizne-Schiff base derivatives. The molecular structures of the studied compounds are computerized using DFT/B3LYP method. The effects of substituent at the triazine and phenyl ring on the electronic and spectroscopic properties of the studied compounds were also investigated. The natural atomic charges showed that pipridino-s-triazine derivatives are richer in electrons than those having morpholino derivatives. The anti-proliferative effects for the prepared compounds were tested against three different cancer cell lines.

  8. The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties

    Science.gov (United States)

    Qaddouri, Bouchra; Guaadaoui, Abdelkarim; Bellirou, Ahmed; Hamal, Abdellah; Melhaoui, Ahmed; Brown, Grant W.; Bellaoui, Mohammed

    2011-01-01

    The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties. PMID:19596744

  9. Evaluation of anti-proliferative and anti-inflammatory activities of Pelagia noctiluca venom in Lipopolysaccharide/Interferon-γ stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Ayed, Yosra; Sghaier, Rabiaa Manel; Laouini, Dhafer; Bacha, Hassen

    2016-12-01

    Components of Pelagia noctiluca (P. noctiluca) venom were evaluated for their anticancer and nitric Oxide (NO) inhibition activities. Three fractions, out of four, obtained by gel filtration on Sephadex G75 of P. noctiluca venom revealed an important selective anti-proliferative activity on several cell lines such as human bladder carcinoma (RT112), human glioblastoma (U87), and human myelogenous leukemia (K562) but not on mitogen-stimulated peripheral blood mononuclear cells. Interestingly, P. noctiluca components showed an important dose-dependent anti-inflammatory activity, through inhibition of NO production via transcriptional regulation of Inducible NO Synthase (iNOS), in IFN-γ/LPS stimulated RAW 264.7 macrophages. These data strongly suggest that P. noctiluca venom could be used as a natural inhibitor of cancer cell lines and a potent anti-inflammatory agent for the treatment of anti-inflammatory diseases.

  10. The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties

    Directory of Open Access Journals (Sweden)

    Bouchra Qaddouri

    2011-01-01

    Full Text Available The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.

  11. [The protoskolicidal effect of 1% polyvinylpyrrolidone-iodine (PVP-1) and 2% taurolidine on abdominal hydatidosis].

    Science.gov (United States)

    Ekçı, Baki; Gürol, Yeşim; Aydin, Ismail; Yalniz, Fırat; Ozcan, Murat; Zengın, Kaan

    2010-01-01

    The aim of this study is to determine the efficacy of 1% polyvinylprolidone-iodine (Betadine, PVP-I) and 2% Taurolidine as scolicidal agents for the prevention of abdominal hydatidosis defined as the rupture of the echinococcal cyst spontaneously or traumatically. The study was carried out in fifty mice randomly assigned into 5 treatment groups as following: group with no expose to any scolicidal agent, groups with 1% PVP-I for 2 and 5 minutes; groups with 2 % Taurolidine for 2 minutes, and 5 minutes. PVP-I has found to be effective according to results of staining with the eosin dye in vitro and abdominal hydatidosis in vivo, while Taurolidine was ineffective as a scolicidal agent.

  12. Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

    Science.gov (United States)

    Refolo, Maria Grazia; D'Alessandro, Rosalba; Malerba, Natascia; Laezza, Chiara; Bifulco, Maurizio; Messa, Caterina; Caruso, Maria Gabriella; Notarnicola, Maria; Tutino, Valeria

    2015-12-01

    Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved. We observed a significant increase in the expression of the endocannabinoids receptor (CB1-R) after quercetin treatment. CB1-R can be considered an estrogen responsive receptor and quercetin, having a structure similar to that of the estrogens, can interact with CB1-R leading to the regulation of cell growth. In order to clarify the contribution of the CB1-R to the quercetin action, we investigated some of the principal molecular pathways that are inhibited or activated by this natural compound. In particular we detected the inhibition of the major survival signals like the PI3K/Akt/mTOR and an induction of the pro apoptotic JNK/JUN pathways. Interestingly, the metabolism of β-catenin was modified by flavonoid both directly and through activated CB1-R. In all the experiments done, the quercetin action has proven to be reinforced by anandamide (Met-F-AEA), a CB1-R agonist, and partially counteracted by SR141716, a CB1-R antagonist. These findings open new perspectives for anticancer therapeutic strategies.

  13. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

    Science.gov (United States)

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  14. Die Wirksamkeit von Taurolidin auf das Harnblasenkarzinom des Menschen im Zellversuch und im Rattenmodell

    OpenAIRE

    Bueschges, Michael

    2010-01-01

    The effects of Taurolidine on bladder cancer was observed in cell cultures with human bladder (cancer-) cells (HCV-29, RT-4, Rt112, J-82), on bladder cancer cells of rats (AY-27) and in a rat model. In the cell-cultures, proliferation rate of the cells was measured with a XTT-Test. Taurolidine showed antiproliferative effects on all cell lines. In the rat model, bladder cancer was generated via injection of tumor cells (AY-27) in the bladder-muscularis of female fisher rats (F344). The rats w...

  15. Taurolidine antiadhesive properties on interaction with E. coli; its transformation in biological environment and interaction with bacteria cell wall.

    Directory of Open Access Journals (Sweden)

    Francesco Caruso

    Full Text Available The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a biological environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl on the exocyclic C(methylene. A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH(2 group in the E. coli bacteria cell wall (peptidoglycan has a negative DeltaG value (-38.2 kcal/mol but a high energy barrier (45.8 kcal/mol suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate, whereas methylol-taurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at

  16. Taurolidine antiadhesive properties on interaction with E. coli; its transformation in biological environment and interaction with bacteria cell wall.

    Science.gov (United States)

    Caruso, Francesco; Darnowski, James W; Opazo, Cristian; Goldberg, Alexander; Kishore, Nina; Agoston, Elin S; Rossi, Miriam

    2010-01-28

    The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a biological environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH(2) group in the E. coli bacteria cell wall (peptidoglycan) has a negative DeltaG value (-38.2 kcal/mol) but a high energy barrier (45.8 kcal/mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methylol-taurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.

  17. Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ritter Peter R

    2010-03-01

    Full Text Available Abstract Background Taurolidine (TRD represents an anti-infective substance with anti-neoplastic activity in many malignant cell lines. So far, the knowledge about the cell death inducing mechanisms and pathways activated by TRD is limited. The aim of this study was therefore, to perform a comparative analysis of cell death induction by TRD simultaneously in different malignant cell lines. Materials and methods Five different malignant cell lines (HT29/Colon, Chang Liver/Liver, HT1080/fibrosarcoma, AsPC-1/pancreas and BxPC-3/pancreas were incubated with increasing concentrations of TRD (100 μM, 250 μM and 1000 μM for 6 h and 24 h. Cell viability, apoptosis and necrosis were analyzed by FACS analysis (Propidiumiodide/AnnexinV staining. Additionally, cells were co-incubated with the caspase Inhibitor z-VAD, the radical scavenger N-Acetylcystein (NAC and the Gluthation depleting agent BSO to examine the contribution of caspase activation and reactive oxygen species in TRD induced cell death. Results All cell lines were susceptible to TRD induced cell death without resistance toward this anti-neoplastic agent. However, the dose response effects were varying largely between different cell lines. The effect of NAC and BSO co-treatment were highly different among cell lines - suggesting a cell line specific involvement of ROS in TRD induced cell death. Furthermore, impact of z-VAD mediated inhibition of caspases was differing strongly among the cell lines. Conclusion This is the first study providing a simultaneous evaluation of the anti-neoplastic action of TRD across several malignant cell lines. The involvement of ROS and caspase activation was highly variable among the five cell lines, although all were susceptible to TRD induced cell death. Our results indicate, that TRD is likely to provide multifaceted cell death mechanisms leading to a cell line specific diversity.

  18. Taurolidine cooperates with antineoplastic drugs in neuroblastoma cells.

    Science.gov (United States)

    Eschenburg, Georg; Luckert, Christian; Reinshagen, Konrad; Bergholz, Robert

    2014-11-01

    Neuroblastoma is the most common extracranial tumor in childhood. Outcome of stage 4 disease remains poor and the development of novel therapeutic approaches is thus urgently needed. Taurolidine (TRD), originally invented to avoid catheter infections, has shown to exhibit antineoplastic activity in various cancers. The growth of neuroblastoma cell lines is inhibited by TRD as recently demonstrated. Further analysis disclosed a significant negative growth effect of TRD on the four neuroblastoma cell lines SH-EP TET21N, SK-N-AS, SK-N-BE(2)-M17 and SK-N-SH. Detected IC50 (51-274 μM; 48 h) are promising and correspond to clinically-achievable plasma levels. Apoptosis was induced (76-86%; 48 h) in a time-dependent manner mediated by a simultaneous activation of the intrinsic and extrinsic pathways. This was confirmed by cleavage of caspases -3, -8 and -9 and abrogation of apoptosis by pan-caspase inhibition. Application of TRD resulted in a significant enhancement of cytotoxic drugs vincristine/doxorubicin (2/3 of 4 cell lines) making TRD a promising candidate to be included in neuroblastoma therapy regimens in the future.

  19. The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

    LENUS (Irish Health Repository)

    Doddakula, Kishore K

    2010-09-01

    Cardiopulmonary bypass results in ischemia\\/reperfusion (I\\/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG).

  20. Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (review).

    Science.gov (United States)

    Möhler, Hanns; Pfirrmann, Rolf W; Frei, Karl

    2014-10-01

    Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti‑oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications.

  1. Unsuccessful application of taurolidine in the treatment of fungal peritonitis in peritoneal dialysis.

    Science.gov (United States)

    Gallieni, M; Chiarelli, G; Olivi, L; Cozzolino, M; Cusi, D

    2011-01-01

    Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients, determining hospitalization, technique failure, catheter loss and death. In the 2005 update, treatment recommendations for FP from the International Society of Peritoneal Dialysis (ISPD) advocate catheter removal immediately after fungi are identified by microscopy or culture. The availability of more effective medical treatments could therefore be of great importance. The aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive PD patient with fluconazole resistant Candida peritonitis, who was treated with an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with broad bactericidal and fungicidal properties. It has been used during surgery for lavage of the peritoneum in cases of peritonitis. Its mechanism of action is related to direct toxic action on micro-organisms, through a chemical reaction between active taurolidine derivatives and structures on the cell wall. Treatment failed because the patient had severe burning pain during i.p. administration of the drug, limiting its dose. PD catheter removal allowed complete recovery. It remains undetermined if, with different doses and methodology, taurolidine could be more effective in treating bacterial and/or fungal peritonitis. Currently, catheter removal remains the most effective therapy of fungal peritonitis.

  2. Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.

    LENUS (Irish Health Repository)

    O'Brien, G C

    2012-02-03

    BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness. METHODS: Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response. RESULTS: Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease. CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.

  3. Taurolidine is effective in the treatment of central venous catheter-related bloodstream infections in cancer patients.

    Science.gov (United States)

    Koldehoff, M; Zakrzewski, J L

    2004-11-01

    Taurolidine is an antimicrobial agent that was originally used in the local treatment of peritonitis and was shown to be effective in the prevention of catheter-related bloodstream infections (CR-BSI). In this pilot study, we used taurolidine solution as an intravenous (i.v.) lock into the totally implantable intravascular devices of 11 consecutive oncological patients with catheter-related bloodstream infections not responding to systemic antimicrobial chemotherapy. All patients recovered completely from the infection. No adverse drug effects were seen. Three patients were successfully retreated for a recurrent infection. Our data suggest a beneficial role of taurolidine i.v. lock for the therapy of catheter-related bloodstream infections in oncological patients. Taurolidine i.v. lock application is feasible and could especially be useful in infections resistant to antibiotic chemotherapy.

  4. Observational study of need for thrombolytic therapy and incidence of bacteremia using taurolidine-citrate-heparin, taurolidine-citrate and heparin catheter locks in patients treated with hemodialysis.

    Science.gov (United States)

    Solomon, Laurie R; Cheesbrough, John S; Bhargava, Ramya; Mitsides, Nicos; Heap, Michael; Green, Gerwyn; Diggle, Peter

    2012-01-01

    Catheter-related blood stream infections may be reduced by interdialytic locking with Taurolidine, a nontoxic antimicrobial agent. A formulation of 1.35% Taurolidine in 4% citrate (TC) is associated with a greater need for thrombolysis to maintain catheter patency than 5000 U/ml heparin. Our aim was to determine whether addition of 500 Units/ml of heparin to TC reduces the need for thrombolysis. TCH (1.35% taurolidine, 4% citrate and 500 U/ml heparin) was compared to TC and Heparin 5000 U/ml using retrospective data. Hundred and six adult hemodialysis patients with internal jugular tunnelled intravascular catheters using TCH were compared with 34 patients using TC and 34 patients using heparin 5000 U/ml respectively. Outcomes were time to first use of thrombolysis and bacteremia rates.TCH reduced the need for thrombolysis compared to TC (hazard ratio, 0.2; 95%CI: 0.06, 0.5; p < 0.001) and was not significantly different from heparin 5000 U/ml (hazard ratio, 1.4; 95%CI: 0.5, 3.9; p = 0.5). The bacteremia rates from all causes were 1.33, 1.22 and 3.25 per 1000 catheter- days (p < 0.001) in the TCH, TC and heparin groups respectively. Addition of 500 U/ml heparin to TC reduces the need for thrombolysis without increasing bacteremia and may achieve patency comparable to heparin 5000 U/ml.

  5. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions

    OpenAIRE

    Olthof, Evelyn D.; Versleijen, Michelle W.; Getty Huisman-de Waal; Ton Feuth; Wietske Kievit; Geert J A Wanten

    2014-01-01

    BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the ...

  6. Die Wirkung von Kombinationschemotherapien mit Taurolidin auf Pankreaskarzinomzellen unter besonderer Berücksichtigung der Induktion von Apoptose

    OpenAIRE

    Rust, Johanna Elisabeth Margarete Adelheid

    2016-01-01

    Introduction: The antibacterial agent taurolidine has been shown to exhibit antineoplastic effects both in vitro and in animal models. Resistance towards established cytotoxic agens is a typical feature of pancreatic cancer. Inhibition of programmed cell death was identfied as an important mechanism of drug resistance in cancer cells. Firstly in this study the effect of taurolidine in monotherapy and in combination with gemcitabine, docetaxel and suramin on viabilitiy and proliferation...

  7. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

    Directory of Open Access Journals (Sweden)

    Evelyn D Olthof

    Full Text Available BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. METHODS: Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. RESULTS: Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions. CONCLUSIONS: Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

  8. Taurolidine Antiadhesive Properties on Interaction with E. coli; Its Transformation in Biological Environment and Interaction with Bacteria Cell Wall

    OpenAIRE

    Francesco Caruso; James W Darnowski; Cristian Opazo; Alexander Goldberg; Nina Kishore; Agoston, Elin S.; Miriam Rossi

    2010-01-01

    The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activit...

  9. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

    Science.gov (United States)

    Melchini, A; Costa, C; Traka, M; Miceli, N; Mithen, R; De Pasquale, R; Trovato, A

    2009-07-01

    Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (pinduction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

  10. A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability

    Science.gov (United States)

    Vasaturo, Michele; Fiengo, Lorenzo; De Tommasi, Nunziatina; Sabatino, Lina; Ziccardi, Pamela; Colantuoni, Vittorio; Bruno, Maurizio; Cerchia, Carmen; Novellino, Ettore; Lupo, Angelo; Lavecchia, Antonio; Piaz, Fabrizio Dal

    2017-01-01

    Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects. PMID:28117438

  11. Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway).

    Science.gov (United States)

    Kumar, C Ganesh; Poornachandra, Y; Chandrasekhar, Cheemalamarri

    2015-11-28

    The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications.

  12. Chemical composition and anti-proliferative and anti-inflammatory effects of the leaf and whole-plant samples of diploid and tetraploid Gynostemma pentaphyllum (Thunb.) Makino.

    Science.gov (United States)

    Xie, Zhuohong; Huang, Haiqiu; Zhao, Yang; Shi, Haiming; Wang, Shaoke; Wang, Thomas T Y; Chen, Pei; Yu, Liangli Lucy

    2012-05-01

    Leaf and whole-plant samples of the diploid and tetraploid Gynostemma pentaphyllum (GP) were investigated and compared for their chemical compositions, and their potential anti-proliferative and anti-inflammatory effects. The highest levels of total flavonoids and phenolics were observed in the diploid leaf botanical (2L3) at 36.84mg rutin equiv/g and 41.15mg gallic acid equiv/g, respectively. The diploid leaf sample (2L2) had the highest amount of rutin and quercetin contents of 77.7μmol quercetin equiv/g. The tetraploid whole-plant botanical (4L3) had the highest total saponin content of 227.1mg gypenoside equiv/g. Extracts from all tested GP samples showed time- and dose-dependent antiproliferative effects in HT-29 cells, and the diploid leaf samples had the overall highest inhibitory activity. These extracts had different order of antiproliferative properties in the LNCaP cells, suggesting the potential selective inhibition of GP extracts against different types of cancer cells and the effect of the cell model in screening and evaluation of antiproliferative components. In addition, the diploid leaf extracts showed the strongest inhibitory effects on the expression of TNF-α, IL-6 and COX-2 mRNA at final concentrations of 0.2 and 1mg botanical equiv/ml media. The results from this study will be used to develop new nutraceutical products from G. pentaphyllum.

  13. A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Youlin Deng

    2016-08-01

    Full Text Available Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

  14. A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability

    Science.gov (United States)

    Vasaturo, Michele; Fiengo, Lorenzo; de Tommasi, Nunziatina; Sabatino, Lina; Ziccardi, Pamela; Colantuoni, Vittorio; Bruno, Maurizio; Cerchia, Carmen; Novellino, Ettore; Lupo, Angelo; Lavecchia, Antonio; Piaz, Fabrizio Dal

    2017-01-01

    Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects.

  15. Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial.

    NARCIS (Netherlands)

    Bisseling, T.M.; Willems, M.C.M.; Versleijen, M.W.J.; Hendriks, J.C.M.; Vissers, R.K.; Wanten, G.J.A.

    2010-01-01

    BACKGROUND & AIMS: Catheter-related bloodstream infections remain the major threat for Home Parenteral Nutrition programs. Taurolidine, a potent antimicrobial agent, holds promise as an effective catheter lock to prevent such infections. Aim of the present study was to compare taurolidine with hepar

  16. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells.

    Science.gov (United States)

    Sánchez-Camargo, Andrea Del Pilar; García-Cañas, Virginia; Herrero, Miguel; Cifuentes, Alejandro; Ibáñez, Elena

    2016-12-07

    In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116). The processes, carried out under optimal conditions, were: (1) pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent) at lab-scale; (2) Single-step supercritical fluid extraction (SFE) at pilot scale; (3) Intensified two-step sequential SFE at pilot scale; (4) Integrated PLE plus supercritical antisolvent fractionation (SAF) at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight), this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA) and carnosol (CS) at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide), suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  17. Resveratrol Increases Anti-Proliferative Activity of Bestatin Through Downregulating P-Glycoprotein Expression Via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells.

    Science.gov (United States)

    Wang, Li; Wang, Changyuan; Jia, Yongming; Liu, Zhihao; Shu, Xiaohong; Liu, Kexin

    2016-05-01

    Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P-glycoprotein (P-gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti-tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti-proliferative activity of bestatin in K562/ADR cells. Co-treatment with resveratrol, IC50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase-3 and caspase-8 increased, which indicated that resveratrol potentiated bestatin-induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P-gp function and downregulating P-gp expression at mRNA and protein levels, which increased anti-proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti-proliferative activity of bestatin through downregulating P-gp expression via suppressing the PI3K/Akt/mTOR signaling pathway.

  18. High albumin levels restrict the kinetics of 13-cis retinoic acid uptake and intracellular isomerization to all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes.

    Science.gov (United States)

    Tsukada, Miki; Schröder, Mandy; Seltmann, Holger; Orfanos, Constantin E; Zouboulis, Christos C

    2002-07-01

    13-cis Retinoic acid is rapidly absorbed into cells and exerts its anti-proliferative effect on human sebocytes by specific isomerization to high levels of all-trans retinoic acid and binding the retinoic acid receptors. In this study, we have shown that bovine serum albumin, an extracellular binding protein for 13-cis retinoic acid, plays an important part in the uptake of 13-cis retinoic acid in human sebocytes, its intracellular isomerization to all-trans retinoic acid, and the induction of its anti-proliferative effect. The addition of highly concentrated bovine serum albumin (20 mg per ml) to the serum-free maintenance medium resulted in a rather controlled uptake of constant levels of 13-cis and all-trans retinoic acid into the cells over the 72 h of treatment. As a consequence, significantly reduced and delayed isomerization of 13-cis retinoic acid to all-trans retinoic acid was detected. In parallel experiments, the anti-proliferative activity of 13-cis retinoic acid on SZ95 sebocytes was abrogated by adding 20 mg bovine serum albumin per ml into the serum-free medium. These results indicate a critical function of serum albumin as retinoid-binding protein in reducing the concentration of active retinoids and restricting their biologic effects on human sebocytes.

  19. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrea del Pilar Sánchez-Camargo

    2016-12-01

    Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  20. Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Khaghanzadeh Narges

    2012-10-01

    Full Text Available Abstract Background Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. Methods The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed. Results Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. Conclusions We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  1. Umbelliprenin is Cytotoxic against QU-DB Large Cell Lung Cancer Cell Line but Anti-Proliferative against A549 Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Abbas Ghaderi

    2012-10-01

    Full Text Available Background:Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins.Recently, umbelliprenin has attracted the researchers' attention for its antitumor activitiesagainst skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer.Methods:The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed.Results:Data from three independent MTT experiments in triplicate revealed that IC50 values for QUDB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells,but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and lessconcentrations of umbelliprenin, no suppressive effect was observed.Conclusions:We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  2. A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity.

    Science.gov (United States)

    Ude, Ziga; Romero-Canelón, Isolda; Twamley, Brendan; Fitzgerald Hughes, Deirdre; Sadler, Peter J; Marmion, Celine J

    2016-07-01

    7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics.

  3. Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity

    Science.gov (United States)

    Maiorani, Orlando; Pivetta, Eliana; Capuano, Alessandra; Modica, Teresa Maria Elisa; Wassermann, Bruna; Bucciotti, Francesco; Colombatti, Alfonso; Doliana, Roberto; Spessotto, Paola

    2017-01-01

    The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. PMID:28074935

  4. Synthesis, characterization, DNA interactions, DNA cleavage, radical scavenging activity, antibacterial, anti-proliferative and docking studies of new transition metal complexes.

    Science.gov (United States)

    Chennam, Kishan Prasad; Ravi, Mudavath; Ushaiah, B; Srinu, V; Eslavath, Ravi Kumar; Devi, Ch Sarala

    2016-01-01

    The compound N-(2-hydroxybenzylidene)-1-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8 naphthyridine-3-carbohydrazide (LH) and its Cu (II), Co (II) and Zn (II) complexes were synthesized and characterized. The absorption spectral titrations and competitive DNA binding studies depicted those complexes of title compound bind to CT-DNA through intercalation. Interestingly [Cu (II)-(L2)] showed relatively high binding constant value (6.61 x 10(5) M(-1)) compared to [Co (II)-(L2)] (4.378× 10(5) M(-1)) and [Zn (II)-(L2)] (3.1x10(5) M(-1)). Ligand and its complexes were also examined for DNA nuclease activity against pBR-322 plasmid DNA, which showed that [Cu (II)-(L2)] had the best hydrolytic cleavage property displaying prominent double-strand DNA cleavage. In addition, antioxidant activities of the ligand and its metal complexes investigated through scavenging effects for DPPH radical in- vitro, indicated their potentiality as good antioxidants. The in vitro anti-bacterial study inferred the better anti-bacterial activity of [Cu (II)-(L2)] and this was also correlated theoretically by employing docking studies wherein [Cu (II)-(L2)] displayed good Gold score and Chem score. Finally the in vitro anti- proliferative activity of studied compounds was tested against HeLa and MCF-7 cell lines. Interestingly [Cu (II)-(L2)] displayed lower IC50 value and lower percentage of viability in both HeLa and MCF-7 cell lines.

  5. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter;

    2012-01-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi......-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream...

  6. Peritoneal taurolidine lavage in children with localised peritonitis due to appendicitis.

    Science.gov (United States)

    Schneider, Axel; Sack, Ulrich; Rothe, Karin; Bennek, Joachim

    2005-06-01

    Despite aggressive surgical treatment, rational antibiotic therapy, and modern intensive care, generalised peritonitis remains a major threat in the paediatric age group. Several adjuvant strategies such as peritoneal saline lavage and peritoneal drainage have been utilised. Taurolidine, derived from the amino acid taurine, has bactericidic, antiendotoxic, and antiinflammatory properties. It has been introduced previously for intraoperative peritoneal lavage in treating peritonitis in adults. The aim of our study was to evaluate the effect of peritoneal taurolidine lavage on the clinical course and serological inflammation markers in children with perforated appendicitis and localised peritonitis. A series of 27 children presenting with appendicitis between January 1999 and July 2001 were included in the study after parental informed consent. All patients underwent open appendectomy. Taurolidine peritoneal lavage was applied in 15 randomly selected children (eight girls and seven boys; mean age 10 years and 10 months). Twelve children received saline peritoneal lavage and served as the control group (six girls and six boys; mean age 9 years and 7 months). Blood was taken preoperatively and on postoperative days 1, 3, 7, and 14. Full blood cell count, C-reactive protein, endotoxin, interleukin-1, interleukin-6, soluble interleukin-2 receptor, tumour necrosis factor alpha, and procalcitonin were investigated to evaluate the serological course of inflammation. Both groups initially presented with severe inflammation as evidenced clinically and serologically. The clinical postoperative course was uneventful in 13/15 patients in the treatment group and 10/12 patients in the control group. The remaining patients presented complications: intraperitoneal abscess or early postoperative bowel obstruction. With regard to the serological inflammatory parameters, no significant differences were found between the two groups except for the soluble interleukin-2-receptor on the 7

  7. Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution.

    OpenAIRE

    Betjes, Michiel; Agteren, Madelon

    2004-01-01

    textabstractBACKGROUND: The use of haemodialysis catheters is complicated by catheter-related sepsis. Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis. The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization, thereby reducing the incidence of catheter-related sepsis. METHODS: In a randomized prospective trial, patients receiving a dialysis catheter were included and cat...

  8. A Taurolidine-Citrate-Heparin Lock Solution Effectively Eradicates Pathogens From the Catheter Biofilm in Hemodialysis Patients.

    Science.gov (United States)

    Zwiech, Rafał; Adelt, Maria; Chrul, Sławomir

    2016-01-01

    Catheter-related bacteremia (CRB) is a typical complication of hemodialysis catheter use. Catheter lumen colonization by pathogens is regarded as a direct cause of CRB. Once settled, the catheter biofilm increases the risk of developing infection, thus necessitating insertion replacement and antibiotic treatment. The study assessed the self-sufficient efficacy of taurolidine-citrate-heparin lock solution in eradicating catheter biofilm bacteria and keeping it sterile in patients on hemodialysis. Twenty-nine chronic patients on hemodialysis with tunneled and nontunneled catheters locked with a heparin filling (the mean time of heparin lock use -30.1 ± 2.0 days) and subsequently converted to a taurolidine-citrate-heparin filling were included. Peripheral vein and catheter lumen blood cultures were obtained before the filling change and after taurolidine-citrate-heparin lock use (mean time 33.8 ± 7.6 days). Twenty-four participants with tunneled and nontunneled catheters locked with taurolidine-citrate-heparin filling served as the control group. During the heparin-locking period, CRB was diagnosed in 3 cases (only nontunneled catheters). The catheter blood cultures findings were positive in 23 patients (10 temporary and 13 permanent catheters), whereas both the catheter and peripheral vein blood cultures were sterile in 3 of 29 subjects (only permanent catheters). Irrespective of catheter type (tunneled or nontunneled), repeated culture revealed no pathogens in any of the 23 patients with initial positive catheter blood culture, after the use of taurolidine-citrate-heparin filling. No positive blood culture was noted in the control group. The taurolidine-citrate-heparin lock solution effectively eradicated pathogens from nontunneled and tunneled catheter biofilms and helped to maintain catheter lumen sterility.

  9. The antineoplastic antibiotic taurolidine promotes lung and liver metastasis in two syngeneic osteosarcoma mouse models and exhibits severe liver toxicity.

    Science.gov (United States)

    Arlt, Matthias J E; Walters, Denise K; Banke, Ingo J; Steinmann, Patrick; Puskas, Gabor J; Bertz, Josefine; Rentsch, Katharina M; Ehrensperger, Felix; Born, Walter; Fuchs, Bruno

    2012-09-01

    Osteosarcoma (OS) is the most frequent primary bone tumor. Despite multiagent neoadjuvant chemotherapy, patients with metastatic disease have a poor prognosis. Moreover, currently used chemotherapeutics have severe toxic side effects. Thus, novel agents with improved antimetastatic activity and reduced toxicity are needed. Taurolidine, a broad-spectrum antimicrobial, has recently been shown to have antineoplastic properties against a variety of tumors and low systemic toxicity. Consequently, we investigated in our study the antineoplastic potential of taurolidine against OS in two different mouse models. Although both OS cell lines, K7M2 and LM8, were sensitive for the compound in vitro, intraperitoneal application of taurolidine failed to inhibit primary tumor growth. Moreover, it enhanced the metastatic load in both models 1.7- to 20-fold and caused severe liver deformations and up to 40% mortality. Thus, systemic toxicity was further investigated in tumor-free mice histologically, by electron microscopy and by measurements of representative liver enzymes. Taurolidine dose-dependent fibrous thickening of the liver capsule and adhesions and atrophies of the liver lobes were comparable in healthy and tumor-bearing mice. Liver toxicity was further indicated by up to eightfold elevated levels of the liver enzymes alanine transaminase, aspartate transaminase and GLDH in the circulation. Ultrastructural analysis of affected liver tissue showed swollen mitochondria with cristolysis and numerous lipid vacuoles in the cytoplasm of hepatocytes. The findings of our study question the applicability of taurolidine for OS treatment and may suggest the need for caution regarding the widespread clinical use of taurolidine as an antineoplastic agent.

  10. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin.

    Science.gov (United States)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter; Møller, Jens Kjølseth; Schrøder, Henrik

    2012-10-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream infections (CRBSI) was 0.1 per 1000 catheter-days using taurolidine and 0.9 per 1000 catheter-days using heparin (p = 0.03). This randomized trial confirmed that the use of taurolidine as catheter-lock compared with heparin reduced the rate of CRBSIs; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups.

  11. The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics

    OpenAIRE

    Shchekotikhin, Andrey E; Glazunova, Valeria A; Dezhenkova, Lyubov G; Shevtsova, Elena K; Valery F. Traven; Balzarini, Jan; Huang, Hsu-Shan; Shtil, Alexander A; Preobrazhenskaya, Maria N.

    2011-01-01

    We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivative...

  12. Effects of taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer.

    Science.gov (United States)

    Kilian, M; Mautsch, I; Braumann, C; Schimke, I; Guski, H; Jacobi, C A; Wenger, F A

    2003-10-01

    Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (Ptaurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.

  13. RESEARCH PROGRESS ON ANTICANCER EFFECT OF TAUROLIDINE%Taurolidine抗肿瘤应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    江涛; 于少卿; 薛学温

    2011-01-01

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

  14. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions

    NARCIS (Netherlands)

    Olthof, E.D.; Versleijen, M.W.J.; Huisman-de Waal, G.J.; Feuth, T.; Kievit, W.; Wanten, G.J.A.

    2014-01-01

    BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when c

  15. Taurolidine locks significantly reduce the incidence of catheter-related blood stream infections in high-risk patients on home parenteral nutrition.

    Science.gov (United States)

    Saunders, J; Naghibi, M; Leach, Z; Parsons, C; King, A; Smith, T; Stroud, M

    2015-02-01

    Emerging evidence suggests taurolidine reduces the risk of repeated episodes of catheter related blood stream infections (CRBSI) in a subgroup of patients receiving home parenteral nutrition (HPN). We defined 3 indications where taurolidine could be considered and retrospectively analysed data from patients who were treated over a 10 year period to examine the validity of these criteria. Twenty-two patients were identified from a total HPN population of 81, representing 33.2 years of experience. The overall CRBSI rate pre- and post-taurolidine usage was reduced from 5.71 to 0.99 infections per 1000 patient parenteral nutrition days (P-value taurolidine is used as secondary prophylaxis and providing initial data suggesting the benefit of its use as primary prophylaxis.

  16. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

    OpenAIRE

    Marley Kevin; Helfand Stuart C; Edris Wade A; Mata John E; Gitelman Alix I; Medlock Jan; Séguin Bernard

    2013-01-01

    Abstract Background Osteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate fo...

  17. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  18. Antineoplastic activity of taurolidine and its derivatives on human ex vivo glioblastoma bulk cells and cancer stem cells

    OpenAIRE

    Kälin, M B

    2010-01-01

    Despite multimodal therapy, patients suffering from glioblastoma (GBM) still have a dismal prognosis. The identification of cancer stem cells (CSC) in brain tumour tissue, yielded hope that the vulnerable target to combat GBM has been found. Several study groups worldwide concentrate nowadays on therapeutic strategies that effectively target CSC. Since in our laboratory has been revealed that taurolidine, a derivate of the amino acid taurin, displays a potent antineoplastic effect in human gl...

  19. Taurolidine and congeners activate hTRPA1 but not hTRPV1 channels and stimulate CGRP release from mouse tracheal sensory nerves.

    Science.gov (United States)

    Kichko, Tatjana I; Pfirrmann, Rolf W; Reeh, Peter W

    2016-02-01

    Taurolidine has long been in clinical use as an antimicrobial irrigation that does not impede wound healing. It can even be administered intravenously (30 g/day) to treat sepsis or to exert newly recognized antineoplastic actions. Only one irritant effect is reported, that is, to temporarily induce burning pain of unknown origin when applied to body cavities or peripheral veins. The structure of the molecule suggested the chemoreceptor channel TRPA1 as a potential target, which was verified measuring stimulated CGRP release from sensory nerves of the isolated mouse trachea and calcium influx in hTRPA1-transfected HEK293 cells. With both methods, the concentration-response relationship of taurolidine exceeded the threshold value below 500 μmol/L and 100 μmol/L, respectively, and reached saturation at 1 mmol/L. The clinical 2% taurolidine solution did not evoke greater or longer lasting responses. The reversible tracheal response was abolished in TRPA1(-/-) but retained in TRPV1(-/-) mice. Consistently, hTRPV1-HEK showed no calcium influx as a response, likewise native HEK293 cells and hTRPA1-HEK deprived of extracellular calcium did not respond to taurolidine 1 mmol/L. The metabolite taurultam and its oxathiazine derivative, expected to cause less burning pain, showed weak tracheal irritancy only at 10 mmol/L, acting also through hTRPA1 but not hTRPV1. In conclusion, taurolidine, its metabolite, and a novel derivative showed no unspecific cellular effects but selectively, concentration-dependently and reversibly activated the irritant receptor TRPA1 in CGRP-expressing, thus nociceptive, neurons. The clinical solution of 2% taurolidine (~70 mmol/L) can, thus, rightly be expected to cause transient burning pain and neurogenic inflammation.

  20. Taurolidine-citrate lock solution (TauroLock significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

    Directory of Open Access Journals (Sweden)

    Fleischhack Gudrun

    2008-07-01

    Full Text Available Abstract Background Taurolidin/Citrate (TauroLock™, a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type. Methods In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal® Wockhardt UK Ltd, Wrexham, Wales and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock™, Tauropharm, Waldbüttelbrunn, Germany. Results In group 1 (heparin, 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47% BSI were 'primary Gram positive BSI due to CoNS (n = 4 or MRSE (n = 10' [incidence density (ID; 2.30 per 1000 inpatient CVAD-utilization days]. In group 2 (TauroLock™, 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12% BSI were caused by CoNS. (ID, 0.45. The difference in the ID between the two groups was statistically significant (P = 0.004. Conclusion The use of Taurolidin/Citrate (TauroLock™ significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients.

  1. Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma.

    Science.gov (United States)

    Aceto, N; Bertino, P; Barbone, D; Tassi, G; Manzo, L; Porta, C; Mutti, L; Gaudino, G

    2009-12-01

    Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death. Apoptosis was studied by annexin V binding, cell cycle analysis, caspase-8 activation, poly(ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Oxidative stress was measured by nitrite production and DNA oxidative damage. Protein expression and phosphorylation were evaluated by immunoprecipitation and immunoblotting. TN induces cell death of mesothelioma cells, but not of non-neoplastic human mesothelial cells. After TN treatment of mesothelioma cells, Akt but not extracellular signal-regulated kinase (Erk) 1/2 activity is inhibited a in time- and dose-dependent manner. Protein phosphatase (PP)1alpha and PP2A are activated several hours after drug addition. Apoptosis induced by TN is driven by oxidative stress and cell exposure to sulfydryl donors, such as glutathione monoethylester and l-N-acetylcysteine, significantly reduced pro-apoptotic effects and Akt inhibition. Conversely, expression of constitutively activated Akt did not affect cytoxicity elicited by TN, which retained its ability to inhibit the kinase. TN induces mesothelioma cell death via oxidative stress, accompanied by inhibition of Akt signalling. This provides a promising molecular rationale for TN as local treatment of malignant mesothelioma.

  2. Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case

    Directory of Open Access Journals (Sweden)

    Menenakos Charalambos

    2006-06-01

    Full Text Available Abstract Background Taurolidine (TRD is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2, N0, V0. 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

  3. Efeito anti-proliferativo das infusões de Achyrocline satureioides DC (Asteraceae sobre o ciclo celular de Allium cepa Anti-proliferative effect of infusions of Achyrocline satureioides on the Allium cepa cell cycle

    Directory of Open Access Journals (Sweden)

    Juliana M. Fachinetto

    2007-03-01

    Full Text Available Achyrocline satureioides (marcela é utilizada na medicina popular brasileira, na forma de chá, como tratamento de patologias digestivas e inflamatórias. O efeito anti-proliferativo de infusões de marcela sobre o ciclo celular da cebola foi avaliado, utilizando-se inflorescências de marcela recém coletadas (2005 e após armazenamento por 30 meses (2003. Preparou-se as infusões em duas concentrações: 5,0 mg/mL (concentração usual como chá e 20 mg/mL. Utilizaram-se 3 grupos de 6 bulbos de cebola para cada população de marcela. Retirou-se um grupo de bulbos controle de cada população. Todos os bulbos enraizados em água destilada foram transferidos para os extratos de marcela e permaneceram por 24 horas, (os bulbos controle permaneceram em água. As radículas foram coletadas, fixadas em etanol-ácido acético (3:1 por 24 h e estocadas em álcool 70%. Foram analisadas 6000 células por grupo de bulbos, e os índices mitóticos calculados submetidos a análise estatística pelo teste chi2 a 5%. Conclui-se que as infusões de marcela possuem ação antiproliferativa sobre o ciclo celular da cebola e que essa ação inibitória da divisão celular aumenta conforme aumento da concentração, bem como após o armazenamento.Achyrocline saturoides (marcela is used in Brazilian folk medicine as a tea in the treatment of digestive and inflammatory diseases. The anti-proliferative effect of infusions of marcela on onion cell cycle was evaluated by using the inflorescences of recently collected marcela and after the storage for 30 months. Marcela inflorescences were collected for the infusion preparations in 2003 and in 2005 (used still fresh. We prepared the infusions at two concentrations 5.0 mg/mL (concentration used as tea and 20 mg/mL. We used two groups of six onion bulbs for each population of marcela, and one group of bulbs of each population was withdrawn as a control group. All bulbs rooted in distilled water and after they were

  4. Differentiation-inducing and anti-proliferative activities of isoliquiritigenin and all-trans-retinoic acid on B16F0 melanoma cells: Mechanisms profiling by RNA-seq.

    Science.gov (United States)

    Chen, Xiaoyu; Yang, Ming; Hao, Wenjin; Han, Jichun; Ma, Jun; Wang, Caixia; Sun, Shiguo; Zheng, Qiusheng

    2016-10-30

    Melanoma is a cancer that arises from melanocytes, specialized pigmented cells that are found predominantly in the skin. The incidence of malignant melanoma has significantly increased over the last decade. With the development of therapy, the survival rate of some kind of cancer has been improved greatly. But the treatment of melanoma remains unsatisfactory. Much of melanoma's resistance to traditional chemotherapy is believed to arise intrinsically, by virtue of potent growth and cell survival-promoting genetic alteration. Therefore, significant attention has recently been focused on differentiation therapy, as well as differentiation inducer compounds. In previous study, we found isoliquiritigenin (ISL), a natural product extracted from licorice, could induce B16F0 melanoma cell differentiation. Here we investigated the transcriptional response of melanoma differentiation process induced by ISL and all-trans-retinoic acid (RA). Results showed that 390 genes involves in 201 biochemical pathways were differentially expressed in ISL treatment and 304 genes in 193 pathways in RA treatment. Differential expressed genes (DGEs, fold-change (FC)≥10) with the function of anti-proliferative and differentiation inducing indicated a loss of grade malignancy characteristic. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated glutathione metabolism, glycolysis/gluconeogenesis and pentose phosphate pathway were the top three relative pathway perturbed by ISL, and mitogen-activated protein kinase (MAPK) signaling pathway was the most important pathway in RA treatment. In the analysis of hierarchical clustering of DEGs, we discovered 72 DEGs involved in the process of drug action. We thought Cited1, Tgm2, Xaf1, Cd59a, Fbxo2, Adh7 may have critical role in the differentiation of melanoma. The evidence displayed herein confirms the critical role of reactive oxygen species (ROS) in melanoma pathobiology and provides evidence for future targets in the

  5. Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mueller Joachim M

    2009-03-01

    Full Text Available Abstract Background The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe. Methods In the settings of a multicentre (three University Hospitals prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD or 0.25% povidone-iodine (control intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall level of IL-1beta in peritoneal fluid. Results Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36, the cancer-related death rate (17 vs. 19, p = .2, the local recurrence rate (7 vs. 12, p = .16, the distant metastasis rate (13 vs. 18, p = 0.2 as well as the time to relapse were not statistically significant different. Conclusion Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection. Trial registration ISRCTN66478538

  6. Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

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    Weyhe Dirk

    2010-10-01

    Full Text Available Abstract Background The anti-infective agent Taurolidine (TRD has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. Methods Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3 were incubated with TRD (100 μM, 250 μM and 1000 μM. Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. Results TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3 as well as genes involved in the ER stress response (PPP1R15A, in ubiquitination (TRAF6 and mitochondrial apoptotic pathways (PMAIP1. Conclusions This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis.

  7. A novel, non-apoptotic role for Scythe/BAT3: a functional switch between the pro- and anti-proliferative roles of p21 during the cell cycle.

    Directory of Open Access Journals (Sweden)

    Sheila T Yong

    Full Text Available BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.

  8. 羽扇豆醇对人高转移肝癌HCCLM3增殖影响的机制研究%Mechanism of Anti-proliferative Effect of Lupeol on Highly Metastatic Human Hepatocellular Carcinoma HCCLM3 Cells

    Institute of Scientific and Technical Information of China (English)

    张玲莉; 邱振鹏; 彭燕

    2015-01-01

    Objective:To study the mechanism of anti-proliferative effect of lupeol on highly metastatic human hepatocellular car-cinoma HCCLM3 cells. Methods:CCK-8 assay was performed to evaluate the effects of lupeol at different concentration on cell viability in 12-48 h. Caspase inhibitors were used to identify the subtypes of caspases activated during lupeol-induced cell death. The effects of lupeol on the mRNA expression of caspase family and Bcl-2 related genes were detected by real-time PCR. The effects of lupeol on HC-CLM3 cell phase distribution were investigated by flow cytometry. Results:Compared with the control group, lupeol could inhibit HC-CLM3 cell proliferation in a concentration-dependent manner with IC50 of 93 μmol·L-1 in 24h. The number of HCCLM3 cells in the period of G2/M was increased by 1-fold when the lupeol concentration was within 60-100 μmol·L-1 . Lupeol could activate the path-way of caspase, and the mRNA expression of caspase-3 was elevated by 50%-150% when compared with that in the control group. Mo-reover, the mRNA expression of p53 and Bax were increased above 1-fold by lupeol at 100 μmol·L-1 , and the Bcl-2 and PARP ex-pression were significantly suppressed by lupeol at 60-100 μmol·L-1(P<0. 05 or P<0. 01). Conclusion:The results indicate that lupeol has anti-proliferative effect on the liver cancer cells, which is beneficial to the prevention and treatment of liver cancer.%目的::研究羽扇豆醇( Lupeol)在人高转移肝癌细胞系HCCLM3中的抗增殖作用机制。方法:运用CCK-8法检测不同浓度Lupeol在12-48 h对HCCLM3细胞活力的影响及相关Caspase参与Lupeol(20~100μmol·L-1)诱导的细胞凋亡类型;运用Realtime PCR评价Lupeol对细胞内Caspase家族及Bcl-2相关基因的mRNA表达的影响;同时运用流式细胞术检测Lupe-ol对细胞周期分布的影响。结果:Lupeol在24~48 h能够抑制HCCLM3的细胞增殖,并呈现浓度依赖性,在24 h处理细胞的IC50为93μmol·L-1

  9. 美洛昔康抑制人结肠癌细胞增殖与Wnt/β-catenin信号的关系研究%Anti-proliferative effect of meloxicam and Wnt/β-catenin signal in colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    周密; 何百成; 秧茂盛

    2015-01-01

    目的:研究美洛昔康( meloxicam,Mel)对人结肠癌细胞LoVo增殖抑制作用及其机制。方法以人结肠癌细胞株LoVo为研究对象,体外药物敏感试验(结晶紫染色)和流式细胞术( FCM)分析Mel对细胞的增殖抑制作用;流式细胞术和HE染色检测Mel对细胞凋亡的影响;萤光素酶报告质粒检测Mel 对 Wnt/β-catenin 通路信号转导的影响;Western blot检测Mel对细胞内β-catenin蛋白水平的影响。结果与对照组相比,Mel能抑制LoVo细胞增殖,72 h、100μmol· L-1 Mel的细胞抑制率高达(57.635±3.86)%(t=10.044,P=0.001);Mel能诱导 LoVo 细胞凋亡,24 h、60μmol · L-1 Mel的细胞凋亡率达到(33.6 ± 1.7)%( t =30.166, P =0.001);Mel能降低TCF/LEF及Myc/Max报告质粒的萤光素酶活性,24 h、60μmol · L-1 Mel 可使 TCF/LEF 和 Myc/Mac报告的荧光素酶活性分别降至(40.05± 2.79)%( t =14.864, P =0.001)和(35.9±2.38)%( t =16.904, P =0.001);Mel能下调细胞内β-catenin 蛋白水平,40μmol · L-1 Mel在24、48 h时,可将β-catenin蛋白水平分别降至(71±3.78)%( t =7.353, P =0.003)、(52.66±3.57)%( t =11.724,P=0.001)。结论 Mel能抑制LoVo细胞增殖并促进其凋亡,其机制可能与抑制 Wnt /β-catenin 通路信号转导,降低细胞内β-catenin蛋白水平有关。%Aim To investigate the inhibitory effect of meloxicam ( Mel ) on human colon cancer LoVo cells and its mechanism. Methods Crystal violet staining assay and flow cytometry assay were performed to de-termine the anti-proliferative effect of Mel. Flow cy-tometry assay and H&E assay were used to evaluate the apoptotic effect of Mel. Luciferase reporter plasmid ISRE-Luc was employed to measure the effect of Mel on the activation of Wnt/β-catenin signaling transduc-tion. Western blot assay was used to detect effect of Mel on the expression level of β-catenin protein. Re-sults Compared with the control group, the inhibitory rate of cell

  10. Primary anti-proliferative activity evaluation of 1-(quinolizidin-1'-yl)methyl- and 1-([Formula: see text]-tert-amino)alkyl-substituted 2-phenyl-, 2-benzyl- and 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles on human cancer cell lines.

    Science.gov (United States)

    Tonelli, Michele; Tasso, Bruno; Mina, Lorenzo; Paglietti, Giuseppe; Boido, Vito; Sparatore, Fabio

    2013-08-01

    Twenty benzimidazole derivatives bearing in position 1 a ([Formula: see text]-tert-amino)alkyl chain (mainly quinolizidin-1-ylmethyl) and in position 2 an aromatic moiety (phenyl, benzyl or benzotriazol-1/2-ylmethyl) were evaluated at the National Cancer Institute (NCI) for anti-proliferative activity against a panel of 60 human cancer cell lines. Four compounds (6, 7, 9 and 10) displayed a large spectrum of activity with [Formula: see text] 10 [Formula: see text] on 24-57 cell lines, while thirteen compounds exhibited sub-micromolar or even nanomolar activity against single cell lines, such as leukemia CCRF-CEM, HL-60 and MOLT-4, CNS cancer SF-268 and, particularly, renal cancer UO-31, sometimes with outstanding selectivity (compounds 5-7, 11, 13 and 18).

  11. Complications of total implantable access ports and efficacy of Taurolidine-citrate lock solution against catheter-related infections

    Directory of Open Access Journals (Sweden)

    Emine Ince

    2014-01-01

    Full Text Available Background: Totally, implantable access ports (TIAPs are used for long standing venous catheterization. This study was designed to present our experiences of the TIAPs applications and efficacy of Taurolidine-citrate lock solution (TCLS against catheter-related infections. Materials and Methods: We evaluated records of the 108 patients implanted with 112 TIAPs, which had been performed using heparin solution or TCLS between 2005 and 2013. Results: Duration of exposure to TIAPs was 17-2051 days (median: 411 days. The primary diagnoses were solid tumours (n = 57, lymphoma (n = 23, haematologic diseases (n = 23, nephrotic syndrome (n = 4, Hirschsprung disease (n = 1. The right external jugular vein was most frequently used vascular access route (72.3%. Mechanical complications were observed in four cases. TIAPs were removed due to remission in 19 cases and infection in 19 cases. Median time from implantation and to the development of infection was 60 days. Heparin solution had been used for care in 33 ports, whereas heparin and TCLS had been used in 79 ports. Based on statistical comparison, use of TCLS was considered to be an important factor for preventing infection (P = 0.03. Conclusion: We consider that TCLS reduces infection prevalence so TIAPs would be used more extensively and effectively to prevent infections.

  12. Tunneled catheters with taurolidine-citrate-heparin lock solution significantly improve the inflammatory profile of hemodialysis patients.

    Science.gov (United States)

    Fontseré, Néstor; Cardozo, Celia; Donate, Javier; Soriano, Alex; Muros, Mercedes; Pons, Mercedes; Mensa, Josep; Campistol, Josep M; Navarro-González, Juan F; Maduell, Francisco

    2014-07-01

    Mortality and morbidity are significantly higher among patients with dialysis catheters, which has been associated with chronic activation of the immune system. We hypothesized that bacteria colonizing the catheter lumen trigger an inflammatory response. We aimed to evaluate the inflammatory profile of hemodialysis patients before and after locking catheters with an antimicrobial lock solution. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were measured in serum, and levels of mRNA gene expression of IL-6, IL-10, and TNF-α were analyzed in peripheral blood mononuclear cells (PBMC). Samples were obtained at baseline and again after 3 months' use of taurolidine-citrate-heparin lock solution (TCHLS) in 31 hemodialysis patients. The rate of catheter-related bloodstream infections (CRBSI) was 1.08 per 1,000 catheter-days in the heparin period and 0.04 in the TCHLS period (P = 0.023). Compared with the baseline data, serum levels of hs-CRP and IL-6 showed median percent reductions of 18.1% and 25.2%, respectively (P < 0.01), without significant changes in TNF-α or IL-10 levels. Regarding cytokine gene expression in PBMC, the median mRNA expression levels of TNF-α and IL-6 decreased by 20% (P < 0.05) and 19.7% (P = 0.01), respectively, without changes in IL-10 expression levels. The use of TCHLS to maintain the catheter lumen sterility significantly reduces the incidence of CRBSI and improves the inflammatory profile in hemodialysis patients with tunneled catheters. Further studies are needed to evaluate the potential beneficial effects on clinical outcomes.

  13. TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma

    Directory of Open Access Journals (Sweden)

    Klein-Hitpass Ludger

    2008-12-01

    Full Text Available Abstract Background Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD, two substances with apoptogenic properties on human fibrosarcoma (HT1080. Methods Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining. Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR. Protein level changes were documented by Western Blot analysis. NFKB activity was analysed by ELISA and proliferation assays (BrdU were performed. Results and discussion The single substances TRAIL and TRD induced apoptotic cell death and decreased proliferation in HT1080 cells significantly. Gene expression of several genes related to apoptotic pathways (TRAIL: ARHGDIA, NFKBIA, TNFAIP3; TRD: HSPA1A/B, NFKBIA, GADD45A, SGK, JUN, MAP3K14 was changed. The combination of TRD and TRAIL significantly increased apoptotic cell death compared to the single substances and lead to expression changes in a variety of genes (HSPA1A/B, NFKBIA, PPP1R15A, GADD45A, AXL, SGK, DUSP1, JUN, IRF1, MYC, BAG5, BIRC3. NFKB activity assay revealed an antipodal regulation of the several subunits of NFKB by TRD and TRD+TRAIL compared to TRAIL alone. Conclusion TRD and TRAIL are effective to induce apoptosis and decrease proliferation in human fibrosarcoma. A variety of genes seems to be involved, pointing to the NFKB pathway as key regulator in TRD/TRAIL-mediated apoptosis.

  14. Synthesis, characterization and in silico designing of diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents.

    Science.gov (United States)

    Malani, Kalpesh; Thakkar, Sampark S; Thakur, Mukund Chandra; Ray, Arabinda; Doshi, Hiren

    2016-10-01

    A series of eight compounds diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxilate (KM10-17) analogues have been prepared by conventional methods and characterized by IR, Mass, NMR and elemental analysis. In silico docking studies on Human topoisomerase IIbeta (PDB Id: 3QX3) have been performed for all molecules (KM10-17) synthesized. The compounds were tested for in vitro anti-proliferative activity on VERO and 786-O cell lines. Out of all the synthesized compounds, KM11 &KM16 showed moderate activity on both cell lines. In vitro anti-microbial activity was also checked against Bacillus subtilis (BS), Staphylococcus aurous (SA), Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Candida albicans (CA) by well diffusion method. The compound KM11 was found to have highest zone of inhibition against BS, SA, PA and EC. The molecules KM13 and KM16 exhibited good activity against CA. The compounds KM14 and KM16 indicated good zone of inhibition against BS.

  15. [Tunnelled internal jugular vein catheters with taurolidine lock: an acceptable challenge to arterio-venous fistula in 70 years old haemodialyzed patients: a prospective pilot study].

    Science.gov (United States)

    Branger, Bernard; Reboul, Pascal; Prelipcean, Camélia; Noguera, Maria Eugenia; Cariou, Sylvain; Granolleras, Céline; Vecina, Frédérique; Zabadani, Bachir; Boubenider, Samir; Rousseau, Philippe; Deshodt, Gérard; Ramperez, Pierre; Hory, Bernard; Picard, Eric; Branchereau, Pascal; Fabbro-Peray, Pascale; Fourcade, Jacques

    2011-07-01

    Arteriovenous fistula (AVF) is still in 2010 the gold standard of vascular(2) access in haemodialysis (HD) patients. Nevertheless it may be difficult to obtain and/or to use AVF in elderly. With this prospective randomised pilot study, we compare two strategies of vascular access in 70 years old or more new HD patients. AVF were compared to tunnelled jugular vein catheters (TIJC) with taurolidine as bacterial lock solution. Results were as follow: [table: see text] The responses with the visual analogic scale of comfort was 8/10 for TIJC and 5/10 with AVF * Ptaurolidine because of partial clotting of catheters. Albuminemia was significantly lower in AVF failure patients compared to AVF success patients (24.8g/L vs 31.1g/L). This pilot study allows to conclude that TIJC is an acceptable challenge to AVF in haemodialysed patients of 70 years or more in a two years long use.

  16. Substance use

    Science.gov (United States)

    Substance abuse; Illicit drug abuse; Narcotic abuse; Hallucinogen abuse ... Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  17. Recent Advances in Researches on Physiologically Active Substances in Holothurians

    Institute of Scientific and Technical Information of China (English)

    Hirata Takashi; Zaima Nobuhiro; Yamashita Kyoko; Noguchi Ryoko; XUE Changhu; Sugawara Tatsuya

    2005-01-01

    In this report, we reviewed recent literature on physiologically active substances from sea cucumbers (SCs) and their activities together with results obtained from our study. Preventive properties against lipid metabolism were reported in rats using a whole SC preparation with no particular constituent specified. Administration of the preparation lowered serum and hepatic cholesterol levels and improved the HDL/LDL ratio. These functions may be attributed to the stimulatory effect of the extract on the secretion of cholesterol in feces. Novel fucosylated chondroitin sulfates (FCSs) from Ludwigothurea grisea significantly induced fibroblast growth factor 2-dependent angiogenesis in human umbilical vein endothelial cells (HUVECs). The proangiogenetic activity seemed attributable to the action of the sulfated fucose branches on the polysaccharide.SCs contain mycosporine-like amino acids (MAAs) that are capable of absorbing UV. A biogenetic precursor of MAAs was first reported in SCs. The anti-proliferative effects of a branched chain fatty acid from a sea cucumber on prostate cancer cells was reported with the activity of 5-lipoxygenase. Glycosphingolipid constituents in SCs have been systematically analyzed over the past ten years. The results showed that the gangliosides in several SCs differed from those of mammals in that a sialic acid of SC gangliosides directly binded to glucose of cerebroside. Neuritogenic activity of the glycosphingolipids was demonstrated in vitro experiments and may lead to the development of therapeutic products for neurological disorders. Our study also showed that sphingoid bases, the hydrolyzed products of glycosphingolipids from SCs, induced significant apoptosis in several tumor cell lines.

  18. Taurolidine lock solutions for the prevention of catheter-related bloodstream infections: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Yong Liu

    Full Text Available BACKGROUND: Catheter-related bloodstream infections (CRBSIs are a significant cause of morbidity and mortality in critically ill patients, contributing to prolonged hospital stays and increased costs. Whether taurolidine lock solutions (TLS are beneficial for the prevention of CRBSIs remains controversial. In this meta-analysis, we aim to assess the efficacy of TLS for preventing CRBSIs. METHODS: We conducted a systematic search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials that reported on the effects of TLS for preventing CRBSIs. The primary outcome in these studies was catheter-related bloodstream infections, with microbial distribution of CRBSI and catheter-associated thrombosis as secondary outcomes. Data were combined using random-effects models owing to significant clinical heterogeneity. RESULTS: Six randomized controlled trials (RCTs conducted from 2004 through 2013 involving 431 patients and 86,078 catheter-days were included in the review. TLS were significantly associated with a lower incidence of CRBSIs when compared to heparin lock solutions (Risk Ratio [RR], 0.34; 95% Confidence Interval [CI], 0.21-0.55. Use of TLS significantly decreased the incidence of CRBSIs from gram-negative (G- bacteria (P = 0.004; RR, 0.27; CI, 0.11-0.65, and was associated with a non-significant decrease in gram-positive (G+ bacterial infections (P = 0.07; RR, 0.41; CI, 0.15-1.09. No significant association was observed with TLS and catheter-associated thrombosis (RR, 1.99; CI, 0.75-5.28. CONCLUSIONS: The use of TLS reduced the incidence of CRBSIs without obvious adverse effects or bacterial resistance. However, the susceptibility of G+ and G- bacteria to taurolidine and the risk for catheter-associated thrombosis of TLS are indeterminate due to limited data. The results should be treated with caution due to the limited sample sizes and methodological deficiencies

  19. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  20. Shared Substance

    DEFF Research Database (Denmark)

    Gjerlufsen, Tony; Klokmose, Clemens Nylandsted; Eagan, James

    2011-01-01

    This paper presents a novel middleware for developing flexible interactive multi-surface applications. Using a scenario-based approach, we identify the requirements for this type of applications. We then introduce Substance, a data- oriented framework that decouples functionality from data, and S...

  1. Salinomycin对乳腺癌阿霉素耐药细胞株MCF-7/DOX的增殖抑制作用及机制%Anti-proliferative effect of salinomycin on doxorubicin-resistant human breast cancer MCF-7/DOX cells

    Institute of Scientific and Technical Information of China (English)

    刘浩; 卢敏莹; 贺智敏

    2015-01-01

    Aim To investigate the anti-proliferative effect of salinomycin on doxorubicin-resistant human breast cancer MCF-7 /DOX cells.Methods MCF-7 and MCF-7 /DOX cells were treated or untreated with salinomycin.Cell viability was detected by MTS assay. Cell apoptosis was detected by Annexin V-FITC /PI as-say.Reactive oxygen species (ROS)was measured by DCFH-DA staining.Mitochondrial membrane potential was measured by JC-1 assay.The expression of apopto-sis related proteins BAX, BCL-2, caspase-3, and caspase-9 were evaluated by Western blot analysis. Results The cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. The flow cytometry results showed that salinomycin in-duced MCF-7 /DOX cell apoptosis,increased ROS pro-duction,and decreased mitochondrial membrane poten-tial.Furthermore,salinomycin decreased the expres-sion of BCL-2,and increased the expression of BAX, cleaved caspase-3,and cleaved caspase-9.Moreover, the antioxidant N-acetylcysteine (NAC ) markedly blocked the above effects.Conclusions Our results suggest that salinomycin-induced apoptosis in MCF-7 /DOX is associated with induction of ROS production, and activation of mitochondria apoptosis pathway, which may become a potential chemotherapeutic agent for the therapy of doxorubicin resistant breast cancer.%目的:本研究旨在探讨 Salinomycin 对乳腺癌阿霉素耐药细胞株 MCF-7/DOX 增殖和凋亡的影响及可能作用机制。方法MTS 实验检测 Salinomycin 对 MCF-7/DOX 细胞增殖的影响;Annexin V-FITC /PI 染色检测 Salinomycin 对MCF-7/DOX 耐药细胞凋亡的影响;DCFH-DA 染色检测 Sali-nomycin 对 MCF-7/DOX 耐药细胞活性氧(reactive oxygen species,ROS)产生的影响;JC-1法测定细胞线粒体膜电位;Western blot 法检测细胞凋亡相关蛋白 BAX、BCL-2、caspase-3和 caspase-9的表达变化。结果Salinomycin 能明显抑制MCF-7/DOX 耐药细胞增殖,且具有浓度

  2. Isolation,Identification and Cancer Cell Anti-proliferative Activity of Fomitopsis officinalis Fruit Body Constituents%药用拟层孔菌子实体的化学成分及其对肿瘤细胞增殖抑制

    Institute of Scientific and Technical Information of China (English)

    池梦怡; 贾力耕; 包海鹰

    2014-01-01

    Eight compounds,isolated and purified from Fomitopsis officinalis fruit bodies by silica gel column chromatography,Sephadex LH-20 column chromatography and recrystallization,were identified by NMR and mass spectrometry as 4,6,8 (14),22 (23)-tetraen-3-one-ergos-tane,ergosta-7,22,dien-3β-ol,3-keto-dehydrosulfurenic acid,dehydroeburicoic acid,dehydroeburiconic acid,and fomefficinic acids A,B and C. 4,6,8 (14),22 (23)-tetraen-3-one-ergostane has been isolated from F.officinalis fruit bodies for the first time.Fomefficinic acids A and C,3-keto-dehydrosulfurenic acid and dehydroeburicoic acid were obtained in high yield and tested for anti-proliferative activity against two human cancer cell lines.Fomefficinic acids A and C,and 3-keto-dehydrosulfurenic acid,inhibited the growth of MCF-7 human breast cancer cells,while fomefficinic acids A and C inhibited the growth of SMMC-7721 human liver cancer cells.%通过硅胶柱层析法、Sephadex LH-20凝胶柱层析法和重结晶法,分离纯化药用拟层孔菌(Fomitopsis officinalis)子实体中的化学成分,依据化合物的物理性质,运用核磁共振谱(nuclear magnetic resonance, NMR)、质谱(mass spectrometry,MS)等波谱法分析鉴定化合物结构,并选用得率较高的4种化合物进行体外抗肿瘤实验。共分离出8个化合物,为4,6,8(14),22(23)-四烯-3-酮-麦角甾烷、麦角甾-7,22-二稀-3β-醇、3-酮基-去氢硫色多孔菌酸、去氢齿孔酸、阿里红酸A、去氢齿孔酮酸、阿里红酸 C、阿里红酸 B。其中化合物4,6,8(14),22(23)-四烯-3-酮-麦角甾烷为首次从药用拟层孔菌子实体中分离得到。阿里红酸A、阿里红酸 C、3-酮基-去氢硫色多孔菌酸抑制人乳腺癌细胞MCF-7活性较好,阿里红酸A、阿里红酸 C 抑制人肝癌细胞 SMMC-7721活性较好。

  3. Synthesis of novel furozan-based nitric oxide-releasing derivatives of 1-oxo-oridonin with anti-proliferative activity%NO供体型呋咱类1-位氧代冬凌草甲素衍生物的合成及抗增殖活性

    Institute of Scientific and Technical Information of China (English)

    李达翃; 王磊; 蔡浩; 蒋博文; 张奕华; 孙益军; 徐进宜

    2012-01-01

    目的:为寻找新型一氧化氮(NO)供体型抗肿瘤候选药物,设计合成了一系列新型呋咱类1-位氧代冬凌草甲素衍生物.方法:首先合成不同呋咱类NO供体中间体(9a-i),再将它们与1-位氧代冬凌草甲素(2)的14-位羟基进行缩合,得到一系列NO供体型呋咱类1-位氧代冬凌草甲素衍生物;用Griess实验测试硝酸盐/亚硝酸盐的含量,从而间接测试了NO释放量;同时采用MTT法测定了目标化合物对4种人肿瘤细胞株增殖的抑制活性.结果:所有呋咱类NO供体衍生物在体外60 min时间点上都能释放大于19 μmol·L-1的NO.活性最好的目标化合物10h对Bel-7402细胞的增殖抑制活性IC50值达到0.74 μmol.L-1,优于阳性对照药紫杉醇;获得了初步构效关系信息.结论:利用NO供体和活性天然产物形成孪药分子有望成为发现新型抗肿瘤药物的途径之一.%AIM:To search for novel nitric oxide (NO) releasing anti-tumor agents,a series of furoxan-based nitric oxide-releasing derivatives of 1-oxo-oridonin were designed and synthesized.METHOD:Different furozan-based NO donors (ga-i) were synthesized and conjugated with the 14-hydroxyl of 1-oxo-oridonin (2).The level of nitrate/nitrite in the cell lysates was tested by Griess assay and the anti-proliferative activity of these derivatives against four human cancer cell lines was also determined.RESULTS:These furoxan-based NO-releasing derivatives could produce more than 19 μmol·L-1 of NO in vitro at the time point of 60 min.The most promising compound 10 h exhibited stronger activity than the positive control Taxol against the Bel-7402 cell line with an IC50 value 0.74 μmol.L-1.The structure-activity relationships were concluded based on the derived experimental data.CONCLUSION:These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

  4. Psychotoxic Substances

    Science.gov (United States)

    1964-11-16

    began an in- tensive research for the clarification of the mechanism of the effect of psychotomimetic substances. In addition to the semi-synthetically...Dibenamine i.v. 200,000 ... 6oo,000 Ethyl ether p.o. 200,000 ... 400,000 Cocaine s.c. 80,000 ... 300,000 Mescaline p.o. 10,000 ... 20,000 Morphia s.c. 5,000...Autonomic functions Excitement, mood Pyramidal and extra- Meso-diencephalic changes: pyramidal effects: effects: Euphoria , depres- Ataxia, spastic

  5. Recent advances in researches on physiologically active substances in holothurians

    Science.gov (United States)

    Takashi, Hirata; Nobuhiro, Zaima; Kyoko, Yamashita; Ryoko, Noguchi; Xue, Changhu; Tatsuya, Sugawara

    2005-07-01

    In this report, we reviewed recent literature on physiologically active substances from sea cucumbers (SCs) and their activities together with results obtained from our study. Preventive properties against lipid metabolism were reported in rats using a whole SC preparation with no particular constituent specified. Administration of the preparation lowered serum and hepatic cholesterol levels and improved the HDL/LDL ratio. These functions may be attributed to the stimulatory effect of the extract on the secretion of cholesterol in feces. Novel fucosylated chondroitin sulfates (FCSs) from Ludwigothurea grisea significantly induced fibroblast growth factor 2-dependent angiogenesis in human umbilical vein endothelial cells (HU-VECs). The proangiogenetic activity seemed attributable to the action of the sulfated fucose branches on the polysaccharide. SCs contain mycosporine-like amino acids (MAAs) that are capable of absorbing UV. A biogenetic precursor of MAAs was first reported in SCs. The anti-proliferative effects of a branched chain fatty acid from a sea cucumber on prostate cancer cells was reported with the activity of 5-lipoxygenase. Glycosphingolipid constituents in SCs have been systematically analyzed over the past ten years. The results showed that the gangliosides in several SCs differed from those of mammals in that a sialic acid of SC gangliosides directly binded to glucose of cerebroside. Neuritogenic activity of the glycosphingolipids was demonstrated in vitro experiments and may lead to the development of therapeutic products for neurological disorders. Our study also showed that sphingoid bases, the hydrolyzed products of glycosphingolipids from SCs, induced significant apoptosis in several tumor cell lines.

  6. p53/miR-34a通路介导羽扇豆醇的抑制人膀胱癌T24细胞增殖作用%Anti-proliferative Effect of Lupeol on Human Bladder Cancer T24 Cell Line via p53/miR-34 a Signaling

    Institute of Scientific and Technical Information of China (English)

    郭敏; 刘佩; 郑国华; 邱振鹏

    2016-01-01

    Objective:To study the anti-proliferative effect of lupeol on human bladder cancer T24 cell line and the regulating mechanism for p53/miR-34a signaling. Methods:CCK-8 assay was performed to evaluate the effects of lupeol at different concentra-tions on cell viability in 24 h and 48 h. Caspase inhibitors were used to identify the subtypes of Caspase during lupeol induced cell death. The effects of lupeol on the expression of total p53 protein and miR-34a were evaluated by western blot and real-time PCR, re-spectively. The effects of lupeol on downstream targets of miR-34a were quantified by real-time PCR. Results:Lupeol could inhibit the proliferation of T24 cells in a dose-dependent manner. The IC50 of lupeol was (77. 23 ± 6. 78) μmol·L-1 in 24 h. Compared with the control group, lupeol could elevate the expressions of p53 and miR-34a (P<0. 01). Moreover, the mRNA expression of miR-34a tar-gets, Bcl-2, CD44 and c-Myc were significantly down-regulated after the treatment with lupeol (P<0. 01). Conclusion:Lupeol can inhibit T24 cell proliferation, which is related with the regulating effects on p53/miR-34a signaling.%目的::探讨羽扇豆醇对人膀胱癌T24细胞增殖的影响及对p53/miR-34a通路调控机制。方法:运用CCK-8法检测不同浓度羽扇豆醇(5~120μmol·L-1)分别作用24 h和48 h对T24细胞增殖的影响;运用CCK-8法结合Caspase抑制药确证参与羽扇豆醇诱导细胞死亡的Caspase亚型;分别运用荧光定量PCR(qPCR)和蛋白免疫印记评价羽扇豆醇对miR-34a及p53蛋白表达的影响;运用qPCR评价羽扇豆醇对miR-34a下游靶基因Bcl-2、CD44、c-Myc的mRNA表达的影响。结果: T24细胞经羽扇豆醇处理后,其细胞增殖受到明显抑制,且呈一定的剂量依赖性;药物作用24 h和48 h时羽扇豆醇的半抑制浓度(IC50)分别为(77.23±6.78),(64.58±4.23)μmol·L-1。与对照组相比,羽扇豆醇能够使T24细胞中p53蛋白表达

  7. 柱前衍生-反相高效液相色谱测定牛磺罗定及固体制剂含量%Determination of Taurolidine by Pre-column Derivatization and Reversed-Phase High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    陈曦; 雷勇; 张宁; 王业秋; 逢居龙

    2011-01-01

    本文建立了对甲苯磺酰氯柱前衍生-反相高效液相色谱紫外检测法测定牛磺罗定及其固体制剂含量的方法.利用牛磺罗定中含有仲胺基的特点,以对甲基苯磺酰氯柱前衍生牛磺罗定,Venusil XBP C18色谱柱分离,在240 nm波长检测,线性范围为0.016~0.160 g·L-1(r=0.9995),衍生化产物在24 h内稳定,相对标准偏差(RSD)为3.8%,回收率为98.5%~101.2%.本方法简便、灵敏度高,且对检测设备要求低,适用于工业生产中大批量牛磺罗定原料药及其固体制剂的含量测定.%A method using pre-column derivatization and reserved-phase high performance liquid chromatography (RP-HPLC) UV detection was developed to determine taurolidine. Taurolidine was derivated with p-toluenesulfonyl chloride and then separated by Hypersil ODS C18 column, and detected under the 240 nm wavelength. The linear range of taurolidine was from 0. 016 to 0. 160 g/L with the recoveries from 98. 5% to 101. 2%. Derivative products were relatively stable during 24 h (RSD= 3.8%). The method was simple, convenient, sensitive and required low-cost detection device, which is possibly more suitable for the determination of industrial production of taurolidine and in its solid dosage forms.

  8. Response surface methodology optimizing derivatization condition of taurolidine%表面响应曲面法优化牛磺罗定衍生化条件的研究

    Institute of Scientific and Technical Information of China (English)

    张宁; 雷勇; 任燕冬; 陈曦

    2011-01-01

    Objective:On the base of the single factor investigation, response surface mathodology was applied to optimize the derivatization condition of taurolidine. Methods : Different derivatization reagent concentrations,reaction time and reaction temperature were taken as factor. The amount of the derivative products( expressed by peak area)was taken as response factor. Results : The optimizing derivatization condition of taurolidine was as follows ; the reaction temperature ( 100 ℃ ) , the derivatization reagent concentration ( 20 g · L -1 ) , the reaction time ( 88 min) . Conclusion : The method is accurate, reliable and can be applied to derivatize taurodiline.%目的:在单因素实验的基础上,利用表面响应曲面法(RSM)对HPLC-UV法测定牛磺罗定含量中的牛磺罗定衍生化条件进行优化.方法:以衍生化试剂不同的浓度、反应时间和反应温度为因子,以反应后衍生化产物的量(用峰面积表示)为响应因子,对衍生化条件进行优化.结果:最佳衍生化条件是反应温度为100℃,衍生化试剂浓度为20g·L-1,反应时间为88min.结论:本方法结果准确可靠,可应用于牛磺罗定的衍生化.

  9. Substance Identification Information from EPA's Substance Registry

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Substance Registry Services (SRS) is the authoritative resource for basic information about substances of interest to the U.S. EPA and its state and tribal...

  10. Substance Use in Women

    Science.gov (United States)

    ... trigger women's substance use or other mental health disorders. Women who use certain substances may be more likely to have panic attacks, anxiety, or depression. Substance Use While Pregnant and Breastfeeding ...

  11. Suppressive Effect of Chitosan-taurolidine Nanogel on Invasiveness of HeLa Cells Treated with CO2 Pneumoperitoneum Pressure%壳聚糖-滔罗定纳米凝胶对CO2气腹后HeLa细胞侵袭性的抑制作用

    Institute of Scientific and Technical Information of China (English)

    杨琰; 黄颢; 严兆华; 吕炎; 张凤兰

    2013-01-01

    Objective To investigate the suppressive effect of the chitosan-taurolidine nanogel on the invasiveness of HeLa cells treated with CO2 pneumoperitoneum pressure. Methods Chitosan (0. 02% ) ,as a nano carrier ,was used to synthesize the taurolidine nanogel. The morphology of the fresh-prepared nanogel was observed by the scanning electron microscopy. The invasive ability of HeLa cells was detected by the Transwell migration assay before and after chitosan-taurolidine nanogel treatment. Results Scanning electron microscopy revealed that the chitosan-taurolidine nanogel presented a homogenous structure with a large quantity of fiber interwoven to form a network. The interspace of the network was 50-300 μm in diameter. After treatment with CO2 pneumoperitoneum pressure ,the number of invading and migrating HeLa cells was (69. 2±1. 5 ) and (90. 5 ±4. 1 ) and it was decreased to (20. 8±2. 5 ) and (61. 3±2. 8 ) after chitosan-taurolidine nanogel treatment with the difference being statistically significant ( P<0. 05 ). Conclusion The chitosan-taurolidine nanogel could restrain the invasion and migration of HeLa cells treated with CO2 pneumoperitoneum pressure ,which suggested that it may become a potential treatment alternative that can reduce tumor metastasis after laparoscopic CO2 pneumoperitoneum pressure treatment.%目的 探讨纳米载体壳聚糖(chitosan,CS)包裹新型抑癌剂滔罗定(taurolidine,TRO)所合成的纳米凝胶对CO2气腹后HeLa细胞侵袭性的抑制作用.方法以0.02%的壳聚糖为纳米载体,制备滔罗定凝胶,采用扫描电镜观察新鲜制备的纳米凝胶形态.以终浓度为0.2 mg/mL的壳聚糖-滔罗定凝胶处理HeLa细胞24 h后,Transwell小室法检测细胞处理前后侵袭及迁徙能力的改变.结果 所制备的壳聚糖-滔罗定凝胶为匀质、透明的胶样液体,电镜下凝胶为大量纤维交织形成支架的匀质结构,支架间空隙直径为50~300 μm.CO2气腹后HeLa细胞

  12. Substance use and multiculturalism.

    Science.gov (United States)

    Adrian, M

    1996-01-01

    This paper reviews intercultural variability of substance use behaviors, including availability of international statistics on consumption of alcohol and other drugs, as well as the use of drugs available locally only. Within a conceptual framework of intercultural relations, it considers the history of transcultural spread of substance use behaviors and possible reactions to the introduction of new drugs within a culture or jurisdiction, including illustrations of the "law of alien poisons." Although intercultural views of substance use have generally concentrated on majority groups' views of substance use in minority groups, minority and non-Western views of substance use need to be considered in the context of increasing international and intercultural communications that increase the rate at which substance use behaviors spread. Both Western and non-Western experiences with substance use and misuse must be taken into account so that better interventions can be developed to deal with addictions and other substance-related problems.

  13. Substance, Reality, and Distinctness

    Directory of Open Access Journals (Sweden)

    Boris Hennig

    2008-04-01

    Full Text Available Descartes claims that God is a substance, and that mind and body are two different and separable substances. This paper provides some background that renders these claims intelligible. For Descartes, that something is real means it can exist in separation, and something is a substance if it does not depend on other substances for its existence. Further, separable objects are correlates of distinct ideas, for an idea is distinct (in an objective sense if its object may be easily and clearly separated from everything that is not its object. It follows that if our idea of God is our most distinct idea, as Descartes claims, then God must be a substance in the Cartesian sense of the term. Also, if we can have an idea of a thinking subject which does not in any sense refer to bodily things, and if bodily things are substances, then mind and body must be two different substances.

  14. B16-4A5 cell apoptosis induced with taurolidine%Taurolidine诱导小鼠黑色素瘤B16-4A5细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    孙宝胜; 刘士新; 马艳; 龚平生; 汪江淮; 龚守良

    2007-01-01

    目的:探讨Taurolidine对小鼠黑色素瘤B16-4A5细胞的生长抑制及其诱导凋亡的作用机制.方法:MTT法检测Taurolidine对B16-4A5细胞生长的影响,流式细胞仪检测细胞凋亡,Western blotting检测Bcl-2家族蛋白表达水平,ApoTarget试剂盒检测caspase-9活性.结果:Taurolidine对小鼠B16-4A5细胞生长有显著的抑制作用,并能显著诱导细胞发生凋亡,其作用呈明显的量效和时间依赖性关系.Taurolidine能明显提高促凋亡蛋白(Bax和Bad)表达水平,抑制抗凋亡蛋白(Bcl-2)水平.结论:Taurolidine通过调节Bcl-2家族蛋白及激活caspase-9诱导小鼠B16-4A5黑色素瘤细胞凋亡,抑制细胞增殖.

  15. 离子液体用于牛磺罗定及有关物质的薄层色谱分离%Separation of Taurolidine and Related Substances Using Ionic Liquid by TLC

    Institute of Scientific and Technical Information of China (English)

    纪平; 马郑; 郭兴杰

    2009-01-01

    建立了TLC法分离碱性药物牛磺罗定及有关物质2-氨基乙磺酰氯、2-氨基乙磺酰叠氮和2-氨基乙磺酰胺.以0.5%[Bmim]BF4甲醇溶液处理过的硅胶G板为固定相,0.2%二乙胺的甲醇溶液为展开剂,4个化合物经薄层色谱展开后达到完全分离,斑点清晰、无拖尾现象.

  16. Pricing hazardous substance emissions

    Energy Technology Data Exchange (ETDEWEB)

    Staring, Knut; Vennemo, Haakon

    1997-12-31

    This report discusses pricing of emissions to air of several harmful substances. It combines ranking indices for environmentally harmful substances with economic valuation data to yield price estimates. The ranking methods are discussed and a relative index established. Given the relative ranking of the substances, they all become valued by assigning a value to one of them, the `anchor` substance, for which lead is selected. Valuations are provided for 19 hazardous substances that are often subject to environmental regulations. They include dioxins, TBT, etc. The study concludes with a discussion of other categories of substances as well as uncertainties and possible refinements. When the valuations are related to CO, NOx, SOx and PM 10, the index system undervalues these pollutants as compared to other studies. The scope is limited to the outdoor environment and does not include global warming and eutrophication. The indices are based on toxicity and so do not apply to CO{sub 2} or other substances that are biologically harmless. The index values are not necessarily valid for all countries and should be considered as preliminary. 18 refs., 6 tabs.

  17. Supervision: Substance and Style

    Science.gov (United States)

    Gellerman, Saul W.

    1976-01-01

    Argues that managerial style and substance are inextricably intertwined, illustrating the discussion with excerpts from an extensive study and job analysis of first-line supervisors in a food packaging plant. (JG)

  18. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells.

    Science.gov (United States)

    Akhtar, Reyhan; Ali, Mohd; Mahmood, Safrunnisa; Sanyal, Sankar Nath

    2014-02-01

    Antecedentes: Silibinina un flavonoide a partir de la leche de cardo mariano (Silybum marianum) exhiben una variedad de acciones farmacológicas, incluyendo actividades anti-proliferativos y apoptóticos contra varios tipos de cánceres en animales intactos y líneas celulares de cáncer. En el presente estudio, se estudió el efecto de silibinina en células humanas de cáncer de colon HT-29. Método: Las incubaciones de las células con diferentes concentraciones silibinin (0,783-1.600 ug/ml) para 24, 48 o 72 horas mostró un descenso progresivo de la viabilidad celular. Resultados: La pérdida de la viabilidad celular fue de tiempo de inhibición dependiente y óptima de crecimiento de las células (78%) se observó a las 72 horas. Bajo microscopio invertido, las células muertas fueron vistos como los agregados de células. IC50 (concentración de silibinina matar a las células 50%) los valores fueron 180, 110 y 40 ug/ml a las 24, 48 y 72 horas, respectivamente. Conclusión: Estos resultados volver a hacer cumplir la potenciales contra el cáncer de silibinina, como se informó anteriormente para varias otras líneas celulares de cáncer (Ramasamy y Agarwal (2008), Cancer Letters, 269: 352-62).

  19. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chi-Chang Chang

    2014-12-01

    Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  20. In-vitro release of anti-proliferative paclitaxel from novel balloon-expandable polycaprolactone stents

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shih-Jung, E-mail: shihjung@mail.cgu.edu.tw [Department of Mechanical Engineering, Chang Gung University, Taiwan (China); Hsiao, Chao-Ying [Department of Mechanical Engineering, Chang Gung University, Taiwan (China); Chen, Jan-Kan [Department of Physiology and Pharmacology, Chang Gung University, Taiwan (China); Liu, Kuo-Sheng [Department of Mechanical Engineering, Chang Gung University, Taiwan (China); Department of Cardiovascular Surgery, Chang Gung Memorial Hospital, Taiwan (China); Lee, Cheng-Hung [Department of Mechanical Engineering, Chang Gung University, Taiwan (China); Second Section of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan (China)

    2011-07-20

    This report investigated the in-vitro release characteristics of paclitaxel from novel balloon-expandable polycaprolactone stents. Polycaprolactone stents were first manufactured by a lab-made micro-injection molding machine. Paclitaxel and polylactide-polyglycolide (PLGA) copolymer were dissolved in acetonitrile and were coated onto the surface of the stents by a spray coating device, which was designed and built especially for this study. An elution method was utilized to characterize the in-vitro release characteristics of paclitaxel. The high performance liquid chromatography (HPLC) analysis showed that biodegradable stents could provide sustained release of paclitaxel for more than 70 days. Various process parameters that controlled the release rate of paclitaxel were studied. The experimental results suggested that the total period of drug release could be prolonged by adopting 75:25 PLGA copolymers, employing multi-layer coatings, and increasing the drug loading. In addition, the effectiveness of eluted paclitaxel on cell behavior was examined. The results showed that the eluted drug could effectively inhibit the proliferation of smooth muscle cells. - Research Highlights: {yields} We investigate the in-vitro release characteristics of paclitaxel from polycaprolactone stents. {yields} Biodegradable stents provide sustained release of paclitaxel for more than 70 days. {yields} The eluted drug effectively inhibits the proliferation of smooth muscle cells.

  1. Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells.

    Science.gov (United States)

    Ogihara, Kikumi; Naya, Yuko; Okamoto, Yoshiharu; Hata, Keishi

    2014-01-01

    Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue. The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.

  2. Anti-Proliferative Effect of an Aqueous Extract of Prunella vulgaris in Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Sun Mi Hwang

    2013-01-01

    Full Text Available The abnormal proliferation of vascular smooth muscle cells (VSMCs in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from Prunella vulgaris (APV in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G1 cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21waf1/cip1 and p27kip1. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-κB activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2 translocation and heme oxygenase-1 (HO-1 expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-κB /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that Prunella vulgaris may be useful in preventing diabetic atherosclerosis.

  3. The Anti-Proliferative Effect of Inhibitor of Telomerase on Cultured Retinal Pigment Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to provide a new method for treating proliferative vitreoretinopathy (PVR), the effects of anti-proliferation and apoptosis induction of inhibitors of telomerase and heat shock protein 90 (Hsp90) on the cultured retinal pigment epithelial (RPE) cells were investigated. The rate of apoptosis cells was measured by using TUNEL on the cultured RPE cells, the co-cultured RPE cells with inhibitor of telomerase (camptothecin) or the co-cultured RPE cells with inhibitor of Hsp90 (geldanamycin). The cell proliferation status was measured in the above three groups by using MTT method. The rate of apoptosis in the RPE cells co-cultured with camptothecin or geldanamycin was increased remarkably (P<0.05). MTT showed the rate of growth inhibition was 8.4 %, 32.3 % and 72.3 % at the concentrations of camptothecin 1 μmol/L, 5 μmol/L, 10 μmol/L, respectively, and 6.5 %, 30.9 %, 71.9 % at the concentrations of geldanamycin 1 μmol/L, 5 μmol/L, 10 μmol/L, respectively. It was concluded that telomerase and Hsp90 can promote the proliferation of the cultured RPE cells, while the inhibitor of them can induce apoptosis and inhibit the growth of the RPE cells.

  4. Chalcone derivatives from the fern Cyclosorus parasiticus and their anti-proliferative activity.

    Science.gov (United States)

    Wei, Han; Zhang, Xuenong; Wu, Guanghua; Yang, Xian; Pan, Songwei; Wang, Yanyan; Ruan, Jinlan

    2013-10-01

    Three new chalcone derivatives, named parasiticins A-C (1-3), were isolated from the leaves of Cyclosorus parasiticus, together with four known chalcones, 5,7-dihydroxy-4-phenyl-8-(3-phenyl-trans-acryloyl)-3,4-dihydro-1-benzopyran-2-one (4), 2'-hydroxy-4',6'-dimethoxychalcone (5), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (7). The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of compounds 1-7 were evaluated against six human cancer cell lines in vitro. Compounds 3 and 6 exhibited substantial cytotoxicity against all six cell lines, especially toward HepG2 with the IC₅₀ values of 1.60 and 2.82 μM, respectively. Furthermore, we demonstrated that compounds 3 and 6 could induce apoptosis in the HepG2 cell line, which may contribute significantly to their cytotoxicity.

  5. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  6. Hybrid surfactants decorated with copper ions: aggregation behavior, antimicrobial activity and anti-proliferative effect.

    Science.gov (United States)

    Kaur, Gurpreet; Kumar, Sandeep; Dilbaghi, Neeraj; Bhanjana, Gaurav; Guru, Santosh Kumar; Bhushan, Shashi; Jaglan, Sundeep; Hassan, P A; Aswal, V K

    2016-09-14

    In the present study, the emphasis is laid on the self aggregation behavior of copper based inorganic-organic hybrids in aqueous media. The two complexes, cationic hexadecyl pyridinium trichloro cuprate (1 : 1), [Cp](+)[CuCl3](-), and bishexadecylpyridinium tetrachloro cuprate (2 : 1), [Cp2](2+)[CuCl4](2-), were synthesized using the ligand insertion method. The complexes were characterized using elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and thermogravimetric analysis. The copper complexes were found to be thermally stable, and in the solid state, they possessed the perovskite arrangement with [Cp2](2+)[CuCl4](2-) exhibiting superior stability and crystallinity. The self aggregation behavior of the prepared complexes was analyzed in solution phase (in aqueous medium) using surface tension, conductivity, XRD and small angle neutron scattering (SANS). The results show that the presence of copper as a co-ion in both the stoichiometries results in lower critical micellization concentrations than their precursor. Micellization was thermodynamically spontaneous and micelles formed were ellipsoidal in shape and underwent a prolate ellipsoidal growth with an increase in the concentration of metallosurfactant, as estimated from the SANS. Furthermore, these metallosurfactants were investigated for biocompatibility (using hemolytic assay), antimicrobial activity (fungus and bacteria) and cytotoxicity using human cancerous cells. The hemolysis activity was found to depend on the aggregated state of the metallosurfactants, displaying the highest activity in the monomeric state, and the minimum for post micellar concentrations. The surfactants were found to enhance the antibacterial activity by twofold or more, with the addition of metal in both the stoichiometries. On the contrary, for anticancer and antifungal activities, barely any regular trend or generalization could be obtained. Nevertheless, the copper complexes exhibited high IC50 values for fR2 (healthy cells) signifying their higher safety in comparison to the cancerous cells.

  7. The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Takahara

    Full Text Available Boron neutron capture therapy (BNCT is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa using an in vivo mouse xenograft model that we have developed.Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA; Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment.The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05, while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment.This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

  8. Anti-Proliferative Effect of Copper Oxide Nanorods Against Human Cervical Carcinoma Cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Nagajyothi, P C; Shim, Jaesool; Kim, Doo Hwan

    2016-09-01

    Metal oxide nanoparticles have been widely investigated for its use in the pharmacological field. The present study was aimed to investigate the cytotoxicity of copper oxide nanorods in human cervical carcinoma cells. The effect of copper oxide nanorods on cell viability was determined by sulforhodamine-B (SRB) assay. The fluorescence and confocal microscopy analyzes showed the cell rounding and nuclear fragmentation following exposure of copper oxide nanorods. Reactive oxygen species (ROS) was increased and could initiate membrane lipid peroxidation, which in turn regulate cytokinetic movements of cells. The messenger RNA (mRNA) expression of p53 and caspase 3 was increased, which further confirms the occurrence of apoptosis at the transcriptional level. Furthermore, caspase-3 enzyme activity was increased, which also confirms the occurrence of apoptosis in tumor cells at the translational level. Taking all our experimental results together, it may suggest that the copper oxide nanorods could be a potential anti-tumor agent to inhibit cancer cell proliferation.

  9. Anti-proliferative effect and phytochemical analysis of Cymbopogon citratus extract.

    Science.gov (United States)

    Halabi, Mohammed F; Sheikh, Bassem Y

    2014-01-01

    The antiproliferative and antioxidant potential of Cymbopogon citratus (Lemon grass) extracts were investigated. The extracts were isolated by solvent maceration method and thereafter subjected to antiproliferative activity test on five different cancer cells: human colon carcinoma (HCT-116), breast carcinoma (MCF-7 and MDA-MB 231), ovarian carcinoma (SKOV-3 and COAV), and a normal liver cell line (WRL 68). The cell viability was determined using MTT assay. The DPPH radical scavenging assay revealed a concentration dependent trend. A maximum percentage inhibition of 45% and an IC50 of 278  μg/mL were observed when aqueous extract was evaluated. In contrast, 48.3% and IC50 of 258.9  μg/mL were observed when 50% ethanolic extract was evaluated. Both extracts at concentration of 50 to 800  μg/mL showed appreciative metal chelating activity with IC50 value of 172.2 ± 31  μg/mL to 456.5 ± 30  μg/mL. Depending on extraction solvent content, extract obtained from 50% ethanolic solvent proved to be more potent on breast cancer MCF-7 cell line (IC50 = 68  μg/mL). On the other hand, 90% ethanolic extract showed a moderate potency on the ovarian cancer (COAV) and MCF-7 cells having an IC50 of 104.6  μg/mL each. These results suggested antiproliferative efficacy of C. citratus ethanolic extract against human cancer cell lines.

  10. Anti-proliferative effects of estrogen receptor-modulating compounds isolated from Rheum palmatum.

    Science.gov (United States)

    Kang, Se Chan; Lee, Chang Min; Choung, Eui Su; Bak, Jong Phil; Bae, Jong Jin; Yoo, Hyun Sook; Kwak, Jong Hwan; Zee, Ok Pyo

    2008-06-01

    The Rheum palmatum L., a traditional medicine in Korea, was screened for their estrogenic activity in a recombinant yeast system with a human estrogen receptor (ER) expression plasmid and a reporter plasmid used in a previous study. The EC50 values of the n-hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions of the methanolic extract of R. palmatum in the yeast-based estrogenicity assay system were 0.145, 0.093, 0.125, 1.459, 2.853 microg/mL, respectively, with marked estrogenic activity in the dichloromethane fraction. Using an activity-guided fractionation approach, five known anthraquinones, chrysophanol (1), physcion (2), emodin (3), aloe-emodin (4) and rhein (5), were isolated from the dichloromethane fraction. Compound 3 had the highest estrogenic relative potency (RP, 17bestradiol = 1.00) (6.3 x 10(-2)), followed by compound 4 (3.8 x 10(-3)), compound 5 (2.6 x 10(-4)), a compound 1 (2.1 x 10(-4)). Also, compound 3 and fraction 3 (which contained compound 3) of the dichloromethane fraction of R. palmatum showed strong cytotoxicity in both ER-positive (MCF-7) and-negative (MDA-MB-231) breast cancer cell lines.

  11. Anti-proliferative effects of Siegesbeckia orientalis ethanol extract on human endometrial RL-95 cancer cells.

    Science.gov (United States)

    Chang, Chi-Chang; Hsu, Hsia-Fen; Huang, Kuo-Hung; Wu, Jing-Mei; Kuo, Shyh-Ming; Ling, Xue-Hua; Houng, Jer-Yiing

    2014-12-01

    Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  12. SUBSTANCE ABUSE IN INDIA

    Directory of Open Access Journals (Sweden)

    Bano Rubeena

    2009-12-01

    Full Text Available The epidemic of substance abuse in young generation has assumed alarming dimensions in India. Changing cultural values, increasing economic stress and dwindling supportive bonds are leading to initiation into substance use. Cannabis, heroin, and Indian-produced pharmaceutical drugs are the most frequently abused drugs in India. Drug use, misuse or abuse is also primarily due to the nature of the drug abused, the personality of the individual and the addict’s immediate environment. The processes of industrialization, urbanization and migration have led to loosening of the traditional methods of social control rendering an individual vulnerable to the stresses and strains of modern life.

  13. Adolescent Substance Abuse.

    Science.gov (United States)

    Thorne, Craig R.; DeBlassie, Richard R.

    1985-01-01

    Cummings (1979), citing evidence from the National Institute of Drug Abuse, reports that one of every eleven adult Americans suffers from a severe addictive problem. Drug addiction is epidemic among teenagers; one of every six teenagers suffers from a severe addictive problem. This paper focuses on adolescent drug/substance abuse. (Author)

  14. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  15. Substance abuse and criminal behavior.

    Science.gov (United States)

    Bradford, J M; Greenberg, D M; Motayne, G G

    1992-09-01

    As forensic psychiatry develops as a clinical subspecialty, clinical skill in understanding, treating, and predicting violent behavior will become more important. This article addresses the importance of understanding the relationship between substance abuse and violent behavior. This article also discusses morbidity and mortality in substance abuse, the demographics of substance abuse and criminality, and the clinical aspects of the forensic psychiatric evaluation.

  16. Parental substance use impairment, parenting and substance use disorder risk.

    Science.gov (United States)

    Arria, Amelia M; Mericle, Amy A; Meyers, Kathleen; Winters, Ken C

    2012-07-01

    Using data from a nationally representative sample, this study investigated substance use disorder (SUD) among respondents with ages 15-54 years as a function of their parents' substance-related impairment and parents' treatment history. In addition, associations among maternal and paternal substance-related impairment, specific parenting behaviors, and risk for SUD in the proband were examined. As expected, parental substance-related impairment was associated with SUD. Paternal treatment history was associated with a decreased risk for SUD in the proband but did not appear to be associated with positive parenting practices. Results of post hoc analyses suggested that parenting behaviors might operate differently to influence SUD risk in children where parents are affected by substance use problems compared with nonaffected families. Future research is warranted to better understand the complex relationships among parental substance use, treatment, parenting behaviors, and SUD risk in offspring. Opportunities might exist within treatment settings to improve parenting skills.

  17. Substance abuse and child maltreatment.

    Science.gov (United States)

    Wells, Kathryn

    2009-04-01

    Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

  18. Isolation of haloorganic groundwater humic substances

    DEFF Research Database (Denmark)

    Krog, M.; Grøn, C.

    1995-01-01

    Humic substances were isolated from groundwater according to a revised method designed to avoid organohalogen artefacts. The prepared humic substances exhibited lower halogen contents than humic substances isolated according to the conventionally used method. Excessive oxidation or hydrolysis was...

  19. Substance Abuse Treatment Facilities Locator

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Substance Abuse and Mental Health Services Administration (SAMHSA) provides on-line resource for locating drug and alcohol abuse treatment programs. The...

  20. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  1. Music, Substance Use, and Aggression

    Science.gov (United States)

    Chen, Meng-Jinn; Miller, Brenda A.; Grube, Joel W.; Waiters, Elizabeth D.

    2016-01-01

    Objective This study investigated whether young people’s substance use and aggressive behaviors are related to their listening to music containing messages of substance use and violence. Method Data were collected using self-administered questionnaires and from a sample of community college students aged 15-25 (N = 1056; 43% male). A structural equation modeling method was used to simultaneously assess the associations between listening to various genres of music, alcohol use, illicit drug use, and aggressive behaviors, taking into account respondents’ age, gender, race/ethnicity, and level of sensation seeking. Results Listening to rap music was significantly and positively associated with alcohol use, problematic alcohol use, illicit drug use, and aggressive behaviors when all other variables were controlled. Additionally, alcohol and illicit drug use were positively associated with listening to musical genres of techno and reggae. Control variables such as sensation seeking, age, gender and race/ethnicity were significantly related to substance use and aggressive behaviors. Conclusion The findings suggest that young people’s substance use and aggressive behaviors may be related to their frequent exposure to music containing references to substance use and violence. Conversely, music listening preference may reflect some personal predispositions or lifestyle preferences. Alternatively, substance use, aggression and music preference are independent constructs, but share common “third factors.” PMID:16608146

  2. Women and substance use disorders

    Directory of Open Access Journals (Sweden)

    Morten Hesse

    2009-07-01

    Full Text Available Substance use disorders belong to the class of externalizing behaviours that are generally more common among men than women. Those women who do have substance disorders therefore deviate more from the norms of society compared with men, tend to live in an environment characterized by high risk of violence and other forms of abuse, and tend to be survivors of childhood trauma. In terms of seeking treatment, women often have difficulty acknowledging their problems with substance use disorders, and professionals are reluctant to ask women about drug or alcohol use. Even when they do seek treatment, women in many countries face practical and financial barriers to access treatment. For women who do enter treatment, outcomes are generally comparable to outcomes for men, suggesting that facilitating entry into treatment can yield substantial benefits for women with addictions.

  3. Adolescent pregnancy and substance use.

    Science.gov (United States)

    Flanagan, P; Kokotailo, P

    1999-03-01

    The question of just what is the relationship of early pregnancy and childbearing and substance use among adolescents remains unanswered. From a public health perspective, both behaviors are unwanted, and populations that are at risk are often at high risk for both. Perhaps prevention of one behavior may be expected to prevent the other. This, however, may be too simplistic a notion, grounded in misconception of the role of early pregnancy and specific cultural context. Furthermore, several studies have documented a decline of drug use during pregnancy and just after delivery among adolescent mothers. Does this trend continue through the parenting years? If so, for whom? What are the individual maternal, child, and family environmental characteristics that predict a decline in use or continued abstinence after early childbearing? Within the context of poverty, lower educational attainment, minority status, and high prevalence of alcohol and drug use, pregnancy may play a positive role. With a change in role, young women may be less likely than nonparenting peers and less likely than prior to their own pregnancy to become deeply involved in the negative behaviors, such as smoking, drinking, and substance use. Perhaps this is a potential opportunity to intervene. To summarize, the health risk behaviors of substance use and adolescent pregnancy and childbearing appear to be linked. Youths who become pregnant before they complete high school represent a particular group of young women who may be at higher risk than the general population for substance use, at least cigarettes, alcohol, and marijuana. Yet, most pregnant teenagers are not substance users. Among those who are, frequency and amounts of use in most samples were low compared with adult samples of pregnant women. Furthermore, there is evidence that teenagers perceive substance use as a risk to their pregnancies and their unborn children. Among users, there is a decrease in use and increase in quit rates

  4. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Martin Weiss

    Full Text Available One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP, is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS. In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH. Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  5. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Science.gov (United States)

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  6. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver

    OpenAIRE

    Villa-Treviño Saúl; Rodríguez-Segura Miguel; Aparicio-Bautista Diana; Arellanes-Robledo Jaime; Jiménez-García Mónica; Godina-Nava Juan

    2010-01-01

    Abstract Background Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT - 120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Methods Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinog...

  7. Apoptosis mediated anti-proliferative effect of compound isolated from Cassia auriculata leaves against human colon cancer cell line

    Science.gov (United States)

    Esakkirajan, M.; Prabhu, N. M.; Manikandan, R.; Beulaja, M.; Prabhu, D.; Govindaraju, K.; Thiagarajan, R.; Arulvasu, C.; Dhanasekaran, G.; Dinesh, D.; Babu, G.

    2014-06-01

    A compound was isolated from Cassia auriculata leaves and characterized by high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). The in vitro anticancer effect of the compound isolated from C. auriculata was evaluated in human colon cancer cells HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology analysis and measurement of lactate dehydrogenase. The isolated compound 4-(2,5 dichlorobenzyl)-2,3,4,5,6,7 hexahydro7(4 methoxyphenyl)benzo[h][1,4,7] triazecin8(1H)-one showed 50% inhibition of HCT 15 cells when tested at 20 μg/ml after 24 h incubation. Cytotoxicity, nuclear morphology and lactate dehydrogenase assays clearly show potent anticancer activity of the isolated compound against colon cancer. Thus, the in vitro findings suggest that the compound isolated from C. auriculata leaves have potent anti-cancer properties with possible clinical applications.

  8. Pro-apoptotic and anti-proliferative effects of corn silk extract on human colon cancer cell lines

    Science.gov (United States)

    Guo, Hao; Guan, Hong; Yang, Wenqin; Liu, Han; Hou, Huiling; Chen, Xue; Liu, Zhenyan; Zang, Chuangang; Liu, Yuchao; Liu, Jicheng

    2017-01-01

    Corn silk is an economically and nutritionally significant natural product as it represents a staple food for a large proportion of the world population. This study investigated the anticancer activity of corn silk extract in human colon cancer cells and human gastric cancer cells. Following treatment with corn silk extract, certain apoptosis-related events were observed, including inhibition of cell proliferation, loss of mitochondrial membrane potential (ΔΨm), release of Ca2+ and release of cytochrome c from the mitochondria into the cytosol. Our results revealed that corn silk extract inhibited the proliferation of cancer cells and increased the level of apoptosis in a concentration-dependent manner. Western blot analysis revealed that corn silk extract upregulated the levels of Bax, cytochrome c, caspase-3 and caspase-9, but downregulated the levels of B-cell lymphoma 2. These results suggest that corn silk extract may induce apoptosis through the mitochondria-mediated pathway.

  9. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Science.gov (United States)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  10. Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake.

    Science.gov (United States)

    Zong, Jian-Fa; Peng, Yun-Ru; Bao, Guan-Hu; Hou, Ru-Yan; Wan, Xiao-Chun

    2016-01-01

    Two new oleanane-type saponins, named oleiferasaponins C₄ (1) and C₅ (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosy-(1→3)]-β-d-glucopyranosid-uronic acid methyl ester (1) and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2) through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB).

  11. Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.

    Science.gov (United States)

    Lee, Yoo Jin; Cui, Jun; Lee, Jun; Han, Ah-Reum; Lee, Eun Byul; Jang, Ho Hee; Seo, Eun Kyoung

    2016-01-01

    Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.

  12. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities

    OpenAIRE

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M.; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-01-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values o...

  13. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities.

    Science.gov (United States)

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-10-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values of 1.5 ± 0.4 µM and 5.6 ± 2.5 µM, respectively, against MCF-7 cells. In addition, the indazole derivative 16 was assessed as a competent inhibitor of endothelial tube formation at 30 µM.

  14. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Energy Technology Data Exchange (ETDEWEB)

    Uma Suganya, K.S. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Govindaraju, K., E-mail: govindtu@gmail.com [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Ganesh Kumar, V. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Prabhu, D.; Arulvasu, C. [Department of Zoology, University of Madras, Guindy campus, Chennai 600 025 (India); Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India)

    2016-05-15

    Highlights: • Biosynthesis of stable and well dispersed predominantly spherical gold nanoparticles of size around ∼12.5 nm. • Anticancer assessment of gold nanoparticles on MDA-MB-231 and MCF-7 cell lines. • AuNPs were found non toxic to normal HMEC cells. • Flow cytometry results revealed significant arrest in cell proliferation in early G0/G1 to S phase. - Abstract: Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G{sub 0}/G{sub 1} to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  15. Pomegranate Ellagitannin-Derived Compounds Exhibit Anti-proliferative and Anti-aromatase Activity in Breast Cancer Cells In Vitro

    OpenAIRE

    Adams, Lynn S.; Zhang, Yanjun; Seeram, Navindra P.; Heber, David; Chen, Shiuan

    2010-01-01

    Estrogen stimulates the proliferation of breast cancer cells and the growth of estrogen-responsive tumors. The aromatase enzyme, which converts androgen to estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a rich source of ellagitannins (ETs), has attracted recent attention due to its anti-cancer and anti-atherosclerotic properties. On consumption, pomegranate ETs hydrolyze, releasing ellagic acid (EA) which is then converted to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-o...

  16. Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma.

    Science.gov (United States)

    Nihal, Minakshi; Ahmad, Nihal; Mukhtar, Hasan; Wood, Gary S

    2005-04-20

    Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

  17. Three new anti-proliferative Annonaceous acetogenins with mono-tetrahydrofuran ring from graviola fruit (Annona muricata).

    Science.gov (United States)

    Sun, Shi; Liu, Jingchun; Kadouh, Hoda; Sun, Xiuxiu; Zhou, Kequan

    2014-06-15

    Bioassay-guided fractionation of the fruit powder of graviola (Annona muricata) yielded three novel compounds: muricins J, K, and L. The compounds are all C35 Annonaceous acetogenins with a mono-tetrahydrofuran ring and four hydroxyls. Their structures were elucidated by spectral methods and chemical modification after isolation via chromatographic techniques and HPLC purification. These three acetogenins demonstrated an antiproliferative against human prostate cancer PC-3 cells.

  18. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver

    Directory of Open Access Journals (Sweden)

    Villa-Treviño Saúl

    2010-04-01

    Full Text Available Abstract Background Recently, extremely low frequency electromagnetic fields (ELF-EMF have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT - 120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Methods Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. Results The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of γ-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively and glutathione S-transferase placental expression (P = 0.01. The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P ≤ 0.03, as compared to the sham-exposure group. Conclusion The application of 4.5 mT - 120 Hz ELF-EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process.

  19. Mechanisms underlying the anti-proliferative effects of berry components in in vitro models of colon cancer.

    Science.gov (United States)

    Brown, Emma M; Gill, Chris I R; McDougall, Gordon J; Stewart, Derek

    2012-01-01

    Consumption of fruit and vegetables is associated with a decreased risk of several cancers, particularly colorectal cancer, possibly linked to their phytochemical content, which is of interest due to several proposed health benefits, including potential anticancer activity. Epidemiological data suggests that cancers of the digestive tract are most susceptible to dietary modification, possibly due to being in direct contact with bioactive food constituents and therefore investigating the effects of these bioactive compounds on the prevalent colorectal cancer is feasible. Berries are a common element of Western diets, with members of the Rubus, Fragria, Sorbus, Ribes and Vaccinum genus featuring in desserts, preserves, yoghurts and juices. These soft fruit are rich in bioactive phytochemicals including several classes of phenolic compounds such as flavonoids (anthocyanins, flavonols and flavanols) and phenolic acids (hydroxybenzoic and hydroxycinnamic acids). Whilst there is little data linking berry consumption to reduced risk of colorectal cancer, in vitro evidence from models representing colorectal cancer suggests that berry polyphenols may modulate cellular processes essential for cancer cell survival, such as proliferation and apoptosis. The exact mechanisms and berry constituents responsible for these potential anticancer activities remain unknown, but use of in vitro models provides a means to elucidate these matters.

  20. Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma.

    Science.gov (United States)

    Yim, Su Youn; Lee, You Jin; Lee, Yoen Kyung; Jung, Seung Eun; Kim, Ji Ha; Kim, Hak Jin; Son, Beung Gu; Park, Young Hoon; Lee, Young Guen; Choi, Young Whan; Hwang, Dae Youn

    2009-01-01

    Lignans isolated from Schisandria chinensis have been prescribed as anti-cancer and anti-hepatitis treatments in Chinese medicine. To investigate the applications of lignans isolated from Schisandria chinensis in hepatic carcinoma therapy, their apoptotic ability was screened using a cell proliferation assay. Compared to the other lignans, gomisin N induced high apoptotic levels in hepatic carcinoma. Cell morphology and flow cytometric analysis demonstrated that this lignan induced cell death at high concentrations, but did not induce any changes at low concentrations. In addition, the expression levels of Bcl-2 and Bax proteins, which are involved in the apoptotic pathway, were markedly increased in only the 320 µM-treated group compared to the vehicle and other concentration groups, while the expression level of p53 protein remained unchanged in this group. These results suggest that gomisin N is an anti-cancer drug candidate capable of inhibiting the proliferation and inducing the apoptosis of human hepatic carcinomas.

  1. Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models.

    Digital Repository Service at National Institute of Oceanography (India)

    Vinayak, R.C.; Puttananjaiah, S.; Chatterji, A; Salimath, B.

    , while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed...

  2. Compositions of polyphenols in wild chive, meadow salsify, garden sorrel and ag yoncha and their anti-proliferative effect

    OpenAIRE

    2012-01-01

    During past decades a lot of experimental studies shown that polyphenols have anti-carcinogenic properties have been published. Their antioxidant and tumour arresting effects have been demonstrated using both in vitro and in vivo studies many times. Aim of the present study was to investigate the content of polyphenols in edible flowers of Ag yoncha, Wild chive, Meadow salsify and Garden sorrel and their effect on proliferation activity of human hepatocellular carcinoma cells which has not be...

  3. Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells.

    Directory of Open Access Journals (Sweden)

    Yau Sang Chan

    Full Text Available A dimeric 64-kDa glucosamine-specific lectin was purified from seeds of Phaseolus vulgaris cv. "brown kidney bean." The simple 2-step purification protocol involved affinity chromatography on Affi-gel blue gel and gel filtration by FPLC on Superdex 75. The lectin was absorbed on Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Gel filtration on Superdex 75 yielded a major absorbance peak that gave a single 32-kDa band in SDS-PAGE. Hemagglutinating activity was completely preserved when the ambient temperature was in the range of 20 °C-60 °C. However, drastic reduction of the activity occurred at temperatures above 65 °C. Full hemagglutinating activity of the lectin was observed at an ambient pH of 3 to 12. About 50% activity remained at pH 0-2, and only residual activity was observed at pH 13-14. Hemagglutinating activity of the lectin was inhibited by glucosamine. The brown kidney bean lectin elicited maximum mitogenic activity toward murine splenocytes at 2.5 µM. The mitogenic activity was nearly completely eliminated in the presence of 250 mM glucosamine. The lectin also increased mRNA expression of the cytokines IL-2, TNF-α and IFN-γ. The lectin exhibited antiproliferative activity toward human breast cancer (MCF7 cells, hepatoma (HepG2 cells and nasopharyngeal carcinoma (CNE1 and CNE2 cells with IC(50 of 5.12 µM, 32.85 µM, 3.12 µM and 40.12 µM respectively after treatment for 24 hours. Flow cytometry with Annexin V and propidum iodide staining indicated apoptosis of MCF7 cells. Hoechst 33342 staining also indicated formation of apoptotic bodies in MCF7 cells after exposure to brown kidney bean lectin. Western blotting revealed that the lectin-induced apoptosis involved ER stress and unfolded protein response.

  4. Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells.

    Science.gov (United States)

    Chan, Yau Sang; Wong, Jack Ho; Fang, Evandro Fei; Pan, Wenliang; Ng, Tzi Bun

    2012-01-01

    A dimeric 64-kDa glucosamine-specific lectin was purified from seeds of Phaseolus vulgaris cv. "brown kidney bean." The simple 2-step purification protocol involved affinity chromatography on Affi-gel blue gel and gel filtration by FPLC on Superdex 75. The lectin was absorbed on Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Gel filtration on Superdex 75 yielded a major absorbance peak that gave a single 32-kDa band in SDS-PAGE. Hemagglutinating activity was completely preserved when the ambient temperature was in the range of 20 °C-60 °C. However, drastic reduction of the activity occurred at temperatures above 65 °C. Full hemagglutinating activity of the lectin was observed at an ambient pH of 3 to 12. About 50% activity remained at pH 0-2, and only residual activity was observed at pH 13-14. Hemagglutinating activity of the lectin was inhibited by glucosamine. The brown kidney bean lectin elicited maximum mitogenic activity toward murine splenocytes at 2.5 µM. The mitogenic activity was nearly completely eliminated in the presence of 250 mM glucosamine. The lectin also increased mRNA expression of the cytokines IL-2, TNF-α and IFN-γ. The lectin exhibited antiproliferative activity toward human breast cancer (MCF7) cells, hepatoma (HepG2) cells and nasopharyngeal carcinoma (CNE1 and CNE2) cells with IC(50) of 5.12 µM, 32.85 µM, 3.12 µM and 40.12 µM respectively after treatment for 24 hours. Flow cytometry with Annexin V and propidum iodide staining indicated apoptosis of MCF7 cells. Hoechst 33342 staining also indicated formation of apoptotic bodies in MCF7 cells after exposure to brown kidney bean lectin. Western blotting revealed that the lectin-induced apoptosis involved ER stress and unfolded protein response.

  5. Anti-proliferative effect of a compound isolated from Cassia auriculata against human colon cancer cell line HCT 15.

    Science.gov (United States)

    Esakkirajan, M; Prabhu, N M; Arulvasu, C; Beulaja, M; Manikandan, R; Thiagarajan, R; Govindaraju, K; Prabhu, D; Dinesh, D; Babu, G; Dhanasekaran, G

    2014-01-01

    The compound was isolated from leaves of Cassia auriculata and its structure was characterized using high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology and lactate dehydrogenase assay of isolated compound was tested against human colon cancer cell line HCT 15. The isolated compound, 4-(4-chlorobenzyl)-2,3,4,5,6,7-hexahydro-7-(2-ethoxyphenyl)benzo[h][1,4,7]triazecin-8(1H)-one at 25μg/ml concentration and by 48h showed 50% inhibition of human colon cancer cells (HCT 15). The results suggest that isolated compound from C. auriculata has potential to prevent colon cancer cell line.

  6. Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells.

    Science.gov (United States)

    Aviello, Gabriella; Rowland, Ian; Gill, Christopher I; Acquaviva, Angela Maria; Capasso, Francesco; McCann, Mark; Capasso, Raffaele; Izzo, Angelo A; Borrelli, Francesca

    2010-07-01

    In recent years, the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In this study, we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Cytotoxicity studies were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and trans-epithelial electrical resistance (TEER) assays whereas (3)H-thymidine incorporation and Western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Rhein (0.1-10 microg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 microg/ml) significantly reduced cell proliferation as well as mitogen-activated protein (MAP) kinase activation; by contrast, at high concentration (10 microg/ml) rhein significantly increased cell proliferation and extracellular-signal-related kinase (ERK) phosphorylation. Moreover, rhein (0.1-10 microg/ml): (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function; (ii) did not induce DNA damage, rather it was able to reduce H(2)O(2)-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and reactive oxygen species (ROS) levels induced by H(2)O(2)/Fe(2+). Rhein was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism that seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.

  7. Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake

    Directory of Open Access Journals (Sweden)

    Jian-Fa Zong

    2016-02-01

    Full Text Available Two new oleanane-type saponins, named oleiferasaponins C4 (1 and C5 (2, were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2]-[β-d-glucopyranosyl-(1→2-β-d-galactopyranosy-(1→3]-β-d-glucopyranosid-uronic acid methyl ester (1 and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2]-[β-d-galactopyranosyl-(1→3]-β-d-glucopyranosiduronic acid methyl ester (2 through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB.

  8. Anti-Proliferative Activity of λ-Carrageenan Through the Induction of Apoptosis in Human Breast Cancer Cells

    Science.gov (United States)

    Jazzara, Marie; Ghannam, Ahmed; Soukkarieh, Chadi; Murad, Hossam

    2016-01-01

    Background Sulfated Polysaccharides (SPs) possess spectrum of pharmacological and therapeutic properties that could attributed to their origins variation, chemical structures and biological activities. Various studies have shown the impact of SPs on proliferation in different cancer cell lines. Objectives In this study, we have evaluated the biological effects of λ-carrageenan, a highly SP, extracted from the red seaweed Laurencia papillosa, on MDA-MB-231 cancer cell line. Materials and Methods MDA-MB-231 cells have treated with λ-carrageenan, the viability and apoptosis have assessed by the appropriate florescent probes on flow cytometer. The expression levels of mRNA of apoptotic genes have detected by real-time PCR analysis. Results Our results have indicated that the signaling pathway of λ-carrageenan inhibited the proliferation of MDA-MB-231 cells by up-regulating the pro-apoptotic genes caspase-8, caspase-9, caspase-3 which have been resulting the increased levels of active caspase-3 protein. Furthermore, This SP had that capacity to disrupt the mitochondrial function by altering the bax/bcl-2 ratio of expression which has considered an important element in apoptosis induction. Conclusions The presented results have signposted that λ-carrageenan was a promising bioactive polymer which could be a potential candidate in preventing or treating breast cancer. PMID:27761203

  9. Synthesis of new diarylamides with pyrimidinyl pyridine scaffold and evaluation of their anti-proliferative effect on cancer cell lines.

    Science.gov (United States)

    Abdelazem, Ahmed Z; Al-Sanea, Mohammad M; Park, Hyun-Mee; Lee, So Ha

    2016-02-15

    A new series of diarylamides, having a pyrimidinyl pyridine scaffold, was designed and synthesized. The target compounds were synthesized in three steps. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10 μM, and the most active compound, 5j, was further tested in a five-dose testing mode to determine its IC50 value over the 60 cell lines. In single-dose testing mode, compound 5j showed the highest growth inhibition against the NCI-60 cancer cell lines, while other tested compounds showed a weak to moderate inhibitory activity against a range of different cancer cell lines. In five-dose testing mode, compound 5j showed strong inhibitory activity in micro molar range against many cancer cell lines. Its major activity was against melanoma cancer cell lines. Therefore, compound 5j is a promising hit compound targeting this severe form of cancer.

  10. CYP24 inhibition preserves 1α,25-dihydroxyvitamin D3 anti-proliferative signaling in lung cancer cells

    OpenAIRE

    Zhang, Qiuhong; Kanterewicz, Beatriz; Buch, Shama; Petkovich, Martin; Parise, Robert; Beumer,Jan; Yan LIN; Diergaarde, Brenda; Hershberger, Pamela A.

    2012-01-01

    Human lung tumors aberrantly express the 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3)-catabolizing enzyme, CYP24. We hypothesized that CYP24 reduces 1,25(OH)2D3-mediated transcription and allows lung cancer cells to escape its growth-inhibitory action. To test this, H292 lung cancer cells and the CYP24-selective inhibitor CTA091 were utilized. In H292 cells, CTA091 reduces 1,25(OH)2D3 catabolism, significantly increases 1,25(OH)2D3-mediated growth inhibition, and increases 1,25(OH)2D3 effects on i...

  11. Inositol hexaphosphate (IP6) enhances the anti-proliferative effects of adriamycin and tamoxifen in breast cancer.

    Science.gov (United States)

    Tantivejkul, Kwanchanit; Vucenik, Ivana; Eiseman, Julie; Shamsuddin, AbulKalam M

    2003-06-01

    The current treatment of breast carcinomas recognizes the importance of combination therapy in order to increase efficacy and decrease side effects of conventional chemotherapy. Inositol hexaphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has shown a significant anti-cancer effect in various in vivo and in vitro models, including breast cancer. In this study, we investigated the in vitro growth inhibitory activity of IP6 in combination with adriamycin or tamoxifen, against three human breast cancer cell lines: estrogen receptor (ER) alpha-positive MCF-7, ER alpha-negative MDA-MB 231 and adriamycin-resistant MCF-7 (MCF-7/Adr) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Much lower concentrations of IP6 were required after 96 h of treatment to inhibit the growth of MCF-7/Adr cells than MCF-7 cells; the IC50 for MCF-7/Adr cells was 1.26 mM compared to 4.18 mM for MCF-7 cells. The ER-negative MDA-MB 231 cells were also highly sensitive to IP6 with IC50 being 1.32 mM. To determine the effects of IP6 in combination with either adriamycin or tamoxifen, the median effect principle and Webb's fraction method were used to determine the combination index (CI) and the statistical differences. Growth suppression was markedly increased when IP6 was administered prior to the addition of adriamycin, especially against MCF-7 cells (CI = 0.175 and p IP6 was administered after tamoxifen in all three cell lines studied (CI = 0.343, 0.701 and 0.819; p IP6 with LC50 values ranging from 0.91 to 5.75 mM (n = 10). Our data not only confirm that IP6 alone inhibits the growth of breast cancer cells; but it also acts synergistically with adriamycin or tamoxifen, being particularly effective against ER alpha-negative cells and adriamycin-resistant cell lines.

  12. New Anti-Inflammatory and Anti-Proliferative Constituents from Fermented Red Mold Rice Monascus purpureus NTU 568

    Directory of Open Access Journals (Sweden)

    Yao-Haur Kuo

    2010-11-01

    Full Text Available Six azaphilonoid derivatives, including two new blue fluorescent monapurfluores A (1 and B (2, two known pyridine-containing molecules, monascopyridines C (3 and D (4, and two known monasfluores A (5 and B (6, were isolated and characterized from red mold rice fermented by Monascus purpureus NTU 568. Structural elucidation of new isolates was based on nuclear magnetic resonance (1H- NMR, 13C-NMR, COSY, HMQC, and HMBC and other spectroscopic analyses. Bioactivity evaluation indicated that 1-6 possessed anti-inflammatory activities with dose-dependent relationships for lipopolysaccharide (LPS-induced nitric oxide production. Furthermore, 1-4 also showed moderate antiproliferative effects against human laryngeal carcinoma (HEp-2 (IC50 = 14.81~20.06 μg/mL and human colon adenocarcinoma (WiDr (IC50 = 12.89~21.14 μg/mL.

  13. Substance Abuse by Anesthesiology Residents.

    Science.gov (United States)

    Lutsky, Irving; And Others

    1991-01-01

    The analysis of 183 responses to a survey of former anesthesiology residents of the Medical College of Wisconsin found that 29 had been self-administered problematic substance abusers during their residencies, 23 had been alcohol dependent, and 6 had been drug dependent. More than 85 percent of respondents considered the drug policy information…

  14. Juvenile Justice and Substance Use

    Science.gov (United States)

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad…

  15. Substance Use as Impression Management.

    Science.gov (United States)

    Sharp, Mark J.; Getz, J. Greg

    1996-01-01

    Examines the function of substance use as an impression management tactic. Introductory psychology students (n=377) responded to a survey instrument measuring self-monitoring, perceived success in impression management, interaction anxiety, and self-esteem. Results suggest that alcohol use may serve an impression management function. (JPS)

  16. Substance use during pregnancy and postnatal outcomes

    DEFF Research Database (Denmark)

    Irner, Tina Birk; Teasdale, Thomas William; Tine, Nielsen;

    2012-01-01

    Substance exposure in utero has been associated with physical birth defects and increased risk of regulatory and neuropsychological difficulties. The aims of this study were to describe women who use substances and are in treatment with respect to the type and number of substances used during...... of substances. More than 50% of the mothers ceased using any substances (with the exception of tobacco) by birth, indicating that the treatment program did have an interventional effect on the mothers. The mothers' ability to either cease or decrease the use of substances during pregnancy appears to have direct...

  17. Brief Intervention Helps Adolescents Curb Substance Use

    Science.gov (United States)

    ... Helps Adolescents Curb Substance Use Brief Intervention Helps Adolescents Curb Substance Use Email Facebook Twitter Two hour- ... School, in Minneapolis, conducted the trial with 315 adolescent and parent/caregiver pairs. Their findings strengthen evidence, ...

  18. Youth employment and substance use.

    Science.gov (United States)

    Kaestner, Robert; Sasso, Anthony Lo; Callison, Kevin; Yarnoff, Benjamin

    2013-01-01

    A significant portion of teens work while in school and the consequences of that work are of potential concern to society. While there is widespread support for combining work and school, and some evidence that employment has positive effects on youth development, previous research has revealed some potentially harmful consequences of employment among teens. In this paper, we investigate the relationship between teen employment and substance use. We extended this literature by studying two different cohorts of youth, and by exploiting arguably exogenous variation in youth employment and earnings caused by changes in minimum wages and the business cycle (unemployment). Estimates suggest that hours of work are positively associated with alcohol and cigarette use. However, if selection on unobserved variables were equal to selection on observed variables, these associations would be close to zero. With respect to the association between earnings and substance use, the evidence is less clear.

  19. Why adolescents use substances of abuse.

    Science.gov (United States)

    Duhigg, Daniel

    2013-08-01

    In summary, adolescent substance use is associated with a variety of risks. Using a nonjudgmental and collaborative approach to treating adolescent substance users can yield positive results. Motivational interviewing and the adolescent community reinforcement approach are evidence-based, nonpharmacologic treatments for teens with substance use disorders.

  20. Family Characteristics and Adolescent Substance Use.

    Science.gov (United States)

    Stephenson, Andy L.; And Others

    1996-01-01

    Study used self-report questionnaire data from high school students to determine the relation between adolescents' perception of family characteristics and adolescent substance use patterns. Results indicate adolescents' perception of maternal substance use, family hardiness, and age of the adolescent were significant predictors of substance use.…

  1. Substance misuse and substance use disorders in sex offenders: a review

    NARCIS (Netherlands)

    F.L. Kraanen; P.M.G. Emmelkamp

    2011-01-01

    Substance abuse has often been associated with committing sex offenses. In this article, the following will be reviewed: 1) studies that assessed substance abuse in sex offenders; 2) differences in substance abuse among different types of sex offenders; 3) differences in substance abuse between sex

  2. Nitrogen Forms in Humic Substances

    Institute of Scientific and Technical Information of China (English)

    ZHUOSU-NENG; WENQI-XIAO

    1992-01-01

    In this paper,the nitrogen forms in newly-formed humic substances,including humic acid (HA),fulvic acid (FA) and humic acid in humin (HAI),were studied by using the 15N CP-MAS NMR technique in combination with chemical approaches.Results show that the majority of nitrogen in HA,FA and HAI was in the amide form with some presented as aliphatic and/ or aromatic amines and some as pyrrole type nitrogen,although the contents of nonhydrolyzable nitrogen in them differed greatly from each other (15-55%).

  3. REACH. Analytical characterisation of petroleum UVCB substances

    Energy Technology Data Exchange (ETDEWEB)

    De Graaff, R.; Forbes, S.; Gennart, J.P.; Gimeno Cortes, M.J.; Hovius, H.; King, D.; Kleise, H.; Martinez Martin, C.; Montanari, L.; Pinzuti, M.; Pollack, H.; Ruggieri, P.; Thomas, M.; Walton, A.; Dmytrasz, B.

    2012-10-15

    The purpose of this report is to summarise the findings of the scientific and technical work undertaken by CONCAWE to assess the feasibility and potential benefit of characterising petroleum UVCB substances (Substances of Unknown or Variable Composition, Complex reaction products or Biological Materials) beyond the recommendations issued by CONCAWE for the substance identification of petroleum substances under REACH. REACH is the European Community Regulation on chemicals and their safe use (EC 1907/2006). It deals with the Registration, Evaluation, Authorisation and Restriction of Chemical substances. The report is based on Member Company experience of the chemical analysis of petroleum UVCB substances, including analysis in support of REACH registrations undertaken in 2010. This report is structured into four main sections, namely: Section 1 which provides an introduction to the subject of petroleum UVCB substance identification including the purpose of the report, regulatory requirements, the nature of petroleum UVCB substances, and CONCAWE's guidance to Member Companies and other potential registrants. Section 2 provides a description of the capabilities of each of the analytical techniques described in the REACH Regulation. This section also includes details on the type of analytical information obtained by each technique and an evaluation of what each technique can provide for the characterisation of petroleum UVCB substances. Section 3 provides a series of case studies for six petroleum substance categories (low boiling point naphthas, kerosene, heavy fuel oils, other lubricant base oils, residual aromatic extracts and bitumens) to illustrate the value of the information derived from each analytical procedure, and provide an explanation for why some techniques are not scientifically necessary. Section 4 provides a summary of the conclusions reached from the technical investigations undertaken by CONCAWE Member Companies, and summarising the

  4. Neuropathology of substance use disorders.

    Science.gov (United States)

    Cadet, Jean Lud; Bisagno, Veronica; Milroy, Christopher Mark

    2014-01-01

    Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions. Addiction also includes craving for the substances and, in some cases, involvement in risky behaviors that can cause death. These patterns of behaviors are associated with specific cognitive disturbances and neuroimaging evidence for brain dysfunctions in a diverse population of drug addicts. Postmortem studies have also revealed significant biochemical and/or structural abnormalities in some addicted individuals. The present review provides a summary of the evidence that has accumulated over the past few years to implicate brain dysfunctions in the varied manifestations of drug addiction. We thus review data on cerebrovascular alterations, brain structural abnormalities, and postmortem studies of patients who abuse cannabis, cocaine, amphetamines, heroin, and "bath salts". We also discuss potential molecular, biochemical, and cellular bases for the varied clinical presentations of these patients. Elucidation of the biological bases of addiction will help to develop better therapeutic approaches to these patient populations.

  5. [Substance abuse in older adults].

    Science.gov (United States)

    Bitar, Raoul; Dürsteler, Kenneth M; Rösner, Susanne; Grosshans, Martin; Herdener, Marcus; Mutschler, Jochen

    2014-09-03

    In respect of demographic change, the number of older patients with substance abuse and addiction is on the raise. In this review we present important clinical and therapeutic aspects of substance abuse and addiction in the elderly and focus on alcohol, benzodiazepines and opioids. Daily and risky alcohol consumption is common among older people. They also have an increased risk getting alcohol-related complications. For early detection, laboratory parameters and questionnaires such as the AUDIT-C are suitable. Therapeutically brief interventions have been proved successful. Also, abuse of benzodiazepines, especially low-dose addiction, is widespread among older persons, although often overlooked, and patients often do not recognize their addiction. The physician has to know the correct indication, adequate dosage and pharmacological interactions. A slow-dose reduction is recommended in case of addiction. Thanks to opioid substitution therapy, patients with an opioidaddiction can reach a higher age. Age influences the effects of the substitute, which may require an adjustment of the dosage. Treatment of elderly patients should be based on their needs and resources and is usually very effective.

  6. Cigarette smoking in pregnant substance users: Association with substance use and desire to quit.

    Science.gov (United States)

    Winhusen, Theresa; Lewis, Daniel

    2017-01-01

    Cigarette smoking is prevalent in pregnant substance users but receives low priority in substance use disorder treatment. This article reports the results of a secondary analysis of a randomized, multisite trial with 200 pregnant substance users, 145 (72.5%) of whom smoked at baseline. As predicted: (1) smokers had significantly greater substance use; (2) approximately half of smokers wanted to quit; and (3) smokers with a quit goal had significantly greater self-efficacy and lower perceived difficulty of quitting. Smoking may be associated with more severe substance use in pregnant substance-using patients, half of whom may be interested in smoking-cessation interventions.

  7. Plasma substance P levels in fibrositis.

    Science.gov (United States)

    Reynolds, W J; Chiu, B; Inman, R D

    1988-12-01

    The mechanism of pain in the fibrositis syndrome is unknown. We measured plasma levels of substance P in 32 patients with fibrositis and 26 sex and age matched controls using a radioimmunoassay. The mean plasma level of substance P in the patients with fibrositis was 371 +/- 91 pg/ml and in controls 397 +/- 84 pg/ml (p = NS). We conclude that determination of plasma levels of substance P in fibrositis is of no diagnostic value. This does not exclude the possible role of substance P as a neurotransmitter in the fibrositis syndrome.

  8. Unification of Force and Substance

    CERN Document Server

    Wilczek, Frank

    2015-01-01

    Maxwell's mature presentation of his equations emphasized the unity of electromagnetism and mechanics, subsuming both as "dynamical systems". That intuition of unity has proved both fruitful, as a source of pregnant concepts, and broadly inspiring. A deep aspect of Maxwell's work is its use of redundant potentials, and the associated requirement of gauge symmetry. Those concepts have become central to our present understanding of fundamental physics, but they can appear to be rather formal and esoteric. Here I discuss two things: The physical significance of gauge invariance, in broad terms; and some tantalizing prospects for further unification, building on that concept, that are visible on the horizon today. If those prospects are realized, Maxwell's vision of the unity of field and substance will be brought to a new level.

  9. Molecular aggregation of humic substances

    Science.gov (United States)

    Wershaw, R. L.

    1999-01-01

    Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

  10. Substance abuse precedes Internet addiction.

    Science.gov (United States)

    Lee, Young Sik; Han, Doug Hyun; Kim, Sun Mi; Renshaw, Perry F

    2013-04-01

    The purpose of the current study was to evaluate possible overlapping substance abuse and internet addiction in a large, uniformly sampled population, ranging in age from 13 to 18 years. Participants (N=73,238) in the current study were drawn from the 6th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) for students from 400 middle schools and 400 high schools in 16 cities within South Korea. Of adolescent internet users, 85.2% were general users (GU), 11.9% were users with potential risk for internet addiction (PR), and 3.0% were users with high risk for internet addiction (HR). There was a difference in the number of students with alcohol drinking among the GU, PR, and HR groups (20.8% vs 23.1% vs 27.4%). There was a difference in the number of students who smoked among the GS, PR, and HR groups (11.7% vs 13.5% vs 20.4%). There was a difference in the number of students with drug use among the GU, PR, and HR groups (1.7% vs 2.0% vs 6.5%). After adjusting for sex, age, stress, depressed mood, and suicidal ideation, smoking may predict a high risk for internet addiction (OR=1.203, p=0.004). In addition, drug use may predict a high risk for internet addiction (OR=2.591, pinternet addiction have vulnerability for addictive behaviors, co-morbid substance abuse should be evaluated and, if found, treated in adolescents with internet addiction.

  11. 77 FR 75783 - Disposal of Controlled Substances

    Science.gov (United States)

    2012-12-21

    ... Administration (DEA). These restrictions resulted in the accumulation of controlled substances in household... used. Although ultimate users are exempt from CSA registration requirements for the possession of... substance to another person for the purpose of disposal if the ultimate user dies while in lawful...

  12. Accessing Substance Abuse Prevention Programs for Schools

    Science.gov (United States)

    Schroeder, Jennifer L.; Johnson, Gail E.

    2009-01-01

    Current estimates indicate that over 6 million children live with at least one parent who is a substance abuser or is substance dependent. Children who are exposed to drug and alcohol abuse are at a greater risk of experiencing academic and behavior difficulties. Additionally, several studies have shown that students with emotional and behavioral…

  13. Moving On: Young People and Substance Abuse

    Science.gov (United States)

    Daley, Kathryn; Chamberlain, Chris

    2009-01-01

    To help explain why some young people move from recreational drug use to substance abuse, twelve in-depth interviews were conducted with young people who had experienced problematic substance use. The data were supplemented by statistical data on 111 young people. The researchers found a variety of "structural" factors that help explain young…

  14. Harm Reduction in MSW Substance Abuse Courses

    Science.gov (United States)

    Eversman, Michael H.

    2012-01-01

    Professional social work largely has endorsed the empirically supported paradigm of harm reduction in relation to substance abuse issues. Despite literature detailing similarities between social work and harm reduction, little is known about its presence in MSW substance abuse coursework. A purposive sample of 133 social work faculty from…

  15. Preventing and Treating Substance Abuse among Adolescents

    Science.gov (United States)

    Sussman, Steve

    2011-01-01

    Substance misuse is one of the most prevalent causes of adolescent injury and death. Additionally, 5-8% of adolescents in the U.S. qualify for a diagnosis of substance abuse disorder. This article discusses formal prevention and treatment program models, focusing on a continuum of care which extends from prevention to treatment alternatives.…

  16. Contextual Factors in Adolescent Substance Use.

    Science.gov (United States)

    Hochhauser, Mark; And Others

    Research on adolescent substance use has focused on prevalence and incidence; however, contextual factors have been largely ignored. A survey of 155 adolescents from a Minneapolis suburb was conducted to assess contextual factors affecting adolescent substance use. Subjects reported their use of alcohol, cigarettes, and marihuana with respect to…

  17. Substance Use during Pregnancy in Adolescence.

    Science.gov (United States)

    Lohr, Mary Jane; And Others

    Despite concern over the co-occurrence of substance use and unplanned pregnancy among adolescents, little information is available about drug use before and during pregnancy in adolescence. The present study examined substance use among a sample of premaritally pregnant adolescents (n=241) who were interviewed as part of an ongoing longitudinal…

  18. Nursing and Substance Use Disorders in Mexico.

    Science.gov (United States)

    Villegas-Pantoja, Miguel A; Mendez-Ruiz, Martha D

    2016-04-01

    The authors of this article see substance use disorders as a major public health problem in Mexico in which nursing is taking on an increasingly important role in addressing. The authors discuss some the challenges and opportunities nurse researchers, educators, and clinicians face in the prevention and treatment of substance use disorders in Mexico.

  19. National Toxic Substance Incidents Program (NTSIP)

    Centers for Disease Control (CDC) Podcasts

    2011-02-03

    This podcast gives an overview of the three components of the National Toxic Substance Incidents Program: state surveillance, national database, and response teams.  Created: 2/3/2011 by Agency for Toxic Substances and Disease Registry.   Date Released: 2/3/2011.

  20. 76 FR 50236 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2011-08-12

    ...: Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Prevention, Drug... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... the Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance......

  1. Best practice in workplace hazardous substances management.

    Science.gov (United States)

    Winder, C

    1995-09-01

    Chemical-induced injury and disease remains a significant problem in workers in industry. As a result of this problem, a number of national and international initiatives have recommended the development of conventions, regulations, and codes of practice to attempt to deal with the problems of hazardous substances at work. Within Australia, workplace hazardous substances regulations are in development which will impose legal obligations and responsibilities on the suppliers of hazardous substances and on the employers who use them. At the same time, internationally consistent ISO standards are in use, or are being developed, for quality systems, environmental management, and occupational health and safety. These standards outline a model for the management of quality, environment, or safety, and the processes involved are applicable to the management of hazardous substances. This process includes: obtaining commitment from senior management; instituting consultative mechanisms; developing a hazardous substances policy; identifying components of the hazardous substances management program; resourcing, implementing, and reviewing the program; and integrating the program into the organisation's strategic plan. Only by blending in a specific management program for hazardous substances into the overall planning of an organization will they be managed effectively and efficiently.

  2. Temperament Style and Substance Abuse Characteristics.

    Science.gov (United States)

    Henderson, Melinda J.; Galen, Luke W.; DeLuca, John W.

    1998-06-01

    The relationship of temperament to different patterns and types of alcohol abuse has received much attention over the last decade in order to provide clues to matching patients optimally to treatment strategies. The purpose of this study was to examine the relationship of temperament with a number of relevant substance abuse characteristics in a substance abusing population. One hundred forty-five male veterans were interviewed on their lifetime use of substances and on their psychiatric symptoms, problems associated with use, context, and family history of substance abuse. Subjects filled out the TPQ and the MPQ, which were subjected to factor analysis and revealed four factors: (1) Negative Affectivity/Impulsivity, (2) Positive Affectivity/Sociability, (3) Persistence/Achievement, and (4) Constraint. There was partial support for the hypotheses. Impulsivity was negatively correlated with age of onset and positively correlated with substance-related problems and a family history of substance abuse. Subjects with a history of depression scored significantly lower on the Positive Affectivity/Sociability factor than those who had not experienced a significant depression. Individuals who used alone scored lower on this factor than those who used in social contexts. The temperament factors of Persistence/Achievement and Constraint were, for the most part, unrelated to substance abuse.

  3. Childhood Predictors of Adult Substance Abuse.

    Science.gov (United States)

    Arteaga, Irma; Chen, Chin-Chih; Reynolds, Arthur J

    2010-08-01

    Identification of the early determinants of substance abuse is a major focus of life course research. In this study, we investigated the child, family, and school-related antecedents of the onset and prevalence of substance abuse by age 26 for a cohort of 1,208 low-income minority children in the Chicago Longitudinal Study. Data onon well-being have been collected prospectively since birth from administrative records, parents, teachers, and children. Results indicated that the prevalence of substance abuse by age 26 was 32 percent (self reports or criminal justice system records) with a median age of first use of 17. Probit regression analysis indicated that substance abuse prevalence was primarily determined by gender (males had a higher rate), trouble making behavior by age 12, school mobility, and previous substance use. Family and peer predictors included involvement in the child welfare system by age 9, parent expectations for school success at age 9, parent substance abuse by children's age 15, and deviant peer affiliation by age 16. Age of first substance use was predicted by gender and race/ethnicity (males and Blacks had earlier incidence), involvement in the child welfare system, and family risk status at age 8. As with prevalence, the pattern of predictors for males was similar to the overall sample but the magnitude of effects was stronger.. The predictors of the timing of substance use dependency were gender, family conflict by age 5, involvement in the child welfare system, social maturity at age 9, adolescent school mobility, and school dropout by age 16. Findings indicate that the promotion of family involvement and positive school and social behavior can reduce the risk of substance abuse.

  4. Former substance users working as counselors

    DEFF Research Database (Denmark)

    Hecksher, Dorte

    2007-01-01

    is derived from an interview study initiated in 2000 in Denmark on former substance users with 4 -8 years of abstinence. Through an analysis of interview data from a larger group of former substance users, it became evident that those working as counselors experienced specific dilemmas and problems......All helping professionals risk participation in "dual relationships". But in the case of former substance users working as counselors, specific dilemmas and problems are accentuated. A qualitative analysis highlights some of the ethical and personal dilemmas faced by these counselors. The data...

  5. Continuum mechanics of single-substance bodies

    CERN Document Server

    Eringen, A Cemal

    1975-01-01

    Continuum Physics, Volume II: Continuum Mechanics of Single-Substance Bodies discusses the continuum mechanics of bodies constituted by a single substance, providing a thorough and precise presentation of exact theories that have evolved during the past years. This book consists of three parts-basic principles, constitutive equations for simple materials, and methods of solution. Part I of this publication is devoted to a discussion of basic principles irrespective of material geometry and constitution that are valid for all kinds of substances, including composites. The geometrical notions, k

  6. Investigating widely available substances as vaginal microbicides.

    Science.gov (United States)

    Holmes, Wendy

    2004-01-01

    Microbicides to protect women from HIV are urgently needed. Several potential pharmaceutical microbicides are now undergoing obligatory clinical trials to check safety, acceptability and efficacy before approval for use. Microbicides may have side-effects and, paradoxically, their use may increase the risk of acquiring HIV. Several widely available substances have been suggested as microbicides, including substances with a low pH such as lemon juice, vinegar, soft drinks and lactobacillus dairy products. Because of the potential for harm it is important that these substances are tested before their use is widely promoted. After small scale safety and acceptability studies, their promotion needs to be evaluated as a communication intervention.

  7. Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances.

    Science.gov (United States)

    Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

    2013-12-01

    The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise.

  8. [Oil and Hazardous Substance Spill Response Emergencies

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — A major oil or hazardous substance spill may constitute an emergency situation requiring prompt actions by the Service to protect threatened natural resources. This...

  9. Toxicities of selected substances to freshwater biota

    Energy Technology Data Exchange (ETDEWEB)

    Hohreiter, D.W.

    1980-05-01

    The amount of data available concerning the toxicity of various substances to freshwater biota is so large that it is difficult to use in a practical situation, such as environmental impact assessment. In this document, summary tables are presented showing acute and/or chronic toxicity of selected substances for various groups of aquatic biota. Each entry is referenced to its original source so that details concerning experimental conditions may be consulted. In addition, general information concerning factors modifying toxicity, synergisms, evidence of bioaccumulation, and water quality standards and criteria for the selected substances is given. The final table is a general toxicity table designed to provide an easily accessible and general indication of toxicity of selected substances in aquatic systems.

  10. Microcomputer for controlled substance record keeping.

    Science.gov (United States)

    Stein, R L; Motta, L J; Yee, A D

    1984-01-01

    The use of a microcomputer to maintain controlled substance inventory and record keeping is described. The system maintains perpetual inventories of the central narcotic vault and proof-of-use controlled drug records outstanding at nursing stations. The computerized system has eliminated (1) the delay previously encountered in the posting of transactions from the numeric log to perpetual inventory logs and (2) the potential addition and subtraction errors inherent in a manual system. Computerizing the controlled drug record-keeping system has saved approximately 166 minutes of labor per day, a cost savings of approximately $26. The new system also helps prevent diversion of controlled substances. The computer may also be used for other tasks while not running the controlled substance program. A microcomputer is well suited to the task of controlled-substance record-keeping functions, and the cost of the system (less than $4000) can be quickly recouped in labor savings.

  11. Substance abuse on the college campus.

    Science.gov (United States)

    Rimsza, Mary Ellen; Moses, Karen S

    2005-02-01

    Substance abuse is a major health and behavioral concern in college students. Alcohol and marijuana are the most commonly abused drugs on college campuses. Others include tobacco, 3,4-methylenedioxymethamphetamine, gamma-hydroxybutyrate, flunitrazepam (Rohypnol), lysergic acid, ketamine, methamphetamine, phencyclidine, cocaine, and psilocybin mushrooms. This article reviews the use of these drugs by college students. Substance use is a major contributing factor in poor academic performance and failure to successfully complete a college education.

  12. Adolescent substance use disorders in the school setting.

    Science.gov (United States)

    Yule, Amy M; Prince, Jefferson B

    2012-01-01

    Adolescent substance use is a major public health problem that concerns parents, schools, clinicians, and policy makers. The authors review school-based prevention programs, school drug policies, clinical signs and symptoms of substance impairment, recommendations for referral and engaging adolescents who are using substances, and treatment interventions for adolescent substance use disorders.

  13. Review of the Proposed "DSM-5" Substance Use Disorder

    Science.gov (United States)

    Jones, K. Dayle; Gill, Carman; Ray, Shannon

    2012-01-01

    The "DSM-5" Task Force has recommended a new substance use disorder to replace substance abuse and dependence. This article provides an overview of substance abuse and dependence, a description of the "DSM-5" substance use disorder, and implications and potential consequences of this change.

  14. Client perceptions of incest and substance abuse.

    Science.gov (United States)

    Janikowski, T P; Bordieri, J E; Glover, N M

    1997-01-01

    Clients receiving substance abuse treatment from 35 treatment facilities throughout the United States were surveyed using the Substance Abuse and Incest Survey-Revised (SAIS-R). A total of 732 participants responded to the survey; 518 (71%) were males, 204 (28%) were females, and 10 (1%) did not indicate gender. Participants had a mean age of 33.8 years, were predominately Caucasian (61.6%), never married (45.2%), were currently unemployed (69.4%), and had completed an average of 11.7 years of education. Of the entire sample, 266 (36.3%) reported having been victims of incest; 151 were males and 113 were females (2 did not indicate gender). The group reporting incest histories had a significantly greater percentage of females that did the group not reporting incest histories (chi 2 = 48.1, p incest histories were asked about their perceptions regarding incest, substance abuse, and counseling. Item responses were examined using descriptive statistics and factor analysis. The factor analysis on SAIS-R perception items identified five factors that accounted for 68.9% of the variance; these factors were Stigma and Resistance to Counseling; Substance Abuse and Incest; Ambivalence; Fear and Anticipation; and Receptivity to Counseling. Results are presented and the implications for substance abuse treatment and counseling are discussed.

  15. Sensory processing disorders among substance dependents

    Directory of Open Access Journals (Sweden)

    Batya Engel-Yeger

    2014-08-01

    Full Text Available Purpose: (1 To compare sensory processing patterns as expressed in daily life between substance dependents and typical controls; (2 profile the prevalence of sensory processing disorders (SPD among substance dependents; and (3 examine gender effect on SPD within and between groups. Methods: Two hundred ninety people aged 19-64 participated in this study. The study group included 145 individuals who lived in the community or took part in an outpatient program because of addiction to drugs/alcohol and had been clean for over three months. The control group included 145 individuals who were not exposed to drugs or alcohol on a regular basis and did not suffer from addictive behavior. All participants filled a demographic questionnaire. Those who met the inclusion criteria completed the Adolescent/Adult Sensory Profile (AASP so that their sensory processing patterns could be assessed. Results: When comparing both groups, the study group showed greater sensory sensitivity and significantly higher prevalence of SPD. Significant group/gender interaction was found in regard to sensation seeking. Discussion: SPD among substance dependents may be expressed in daily life by either hypersensitivity or hyposensitivity. The behavioral outcomes reflected by the AASP support neurophysiological manifestations about SPD of substance dependents. The evaluation process of substance dependents should refer to their sensory processing abilities. In case SPD is diagnosed, Occupational Therapy and specific sensory–based interventions should be considered in order to fit the specific needs of individuals and enhance their performance, meaningful participation, and quality of life.

  16. Removal of humic substances by biosorption

    Institute of Scientific and Technical Information of China (English)

    VUKOVI(C) Marija; DOMANOVAC Tomislav; BRI(S)KI Felicita

    2008-01-01

    Fungal pellets of Aspergillus niger 405, Aspergillus ustus 326, and Stachybotrys sp. 1103 were used for the removal of humic substances from aqueous solutions. Batchwise biosorption, carried out at pH 6 and 25℃, was monitored spectrophotometrically and the process described with Freundlich's model. Calculated sorption coefficients K/and n showed that A. niger exhibited the highest efficiency. A good match between the model and experimental data and a high correlation coefficient (R2) pointed out to judicious choice of the mechanism for removal of humic substances from the reaction medium. The sorption rate constants (k) for A. ustus and Stachybotrys sp. were almost equal, however higher than that for A. niger. Comparison of test results with the simulated ones demonstrated the applicability of the designed kinetic model for removal of humic substances from natural water by biosorption with fungal pellets. Different morphological structure of the examined fungal pellets showed that faster sorption does not imply the most efficient removal of humic substances. Desorption of humic substances from fungal pellets was complete, rapid, and yielded uniform results.

  17. Substance Abuse Training and Perceived Knowledge: Predictors of Perceived Preparedness to Work in Substance Abuse

    Science.gov (United States)

    Bina, Rena; Yum, Joohee; Hall, Diane M. Harnek; Sowbel, Lynda; Mollette, Angela; Jani, Jayshree; Smith-Osborne, Alexa

    2008-01-01

    As frontline mental health care providers, social workers need to be prepared to confront and properly manage substance abuse issues in practice. This study examined predictors of recent master of social work (MSW) graduates' perceptions of preparedness to practice in the area of substance abuse. A cross-sectional design was used, and 232 recent…

  18. Classification of Chemical Substances and Adverse Effects of Chemical Substances on Human Health

    OpenAIRE

    Söyleriz, Yüksel

    2015-01-01

    In this study, classification of chemical substances and adverse effects of chemical substances on human health in European Union and Turkey are assessed. Method In this study, national and international legislation and practices in the countries of the European Union are reviewed.

  19. Playing video games while using or feeling the effects of substances: associations with substance use problems.

    Science.gov (United States)

    Ream, Geoffrey L; Elliott, Luther C; Dunlap, Eloise

    2011-10-01

    This study tested the hypothesis that playing video games while using or feeling the effects of a substance--referred to herein as "concurrent use"-is related to substance use problems after controlling for substance use frequency, video gaming as an enthusiastic hobby, and demographic factors. Data were drawn from a nationally representative online survey of adult video gamers conducted by Knowledge Networks, valid n = 2,885. Problem video game playing behavior was operationalized using Tejeiro Salguero and Bersabé Morán's 2002 problem video game play (PVP) measure, and measures for substance use problems were taken from the National Survey of Drug Use and Health (NSDUH). Separate structural equation modeling analyses were conducted for users of caffeine, tobacco, alcohol, and marijuana. In all four models, concurrent use was directly associated with substance use problems, but not with PVP. Video gaming as an enthusiastic hobby was associated with substance use problems via two indirect paths: through PVP for all substances, and through concurrent use for caffeine, tobacco, and alcohol only. Results illustrate the potential for "drug interaction" between self-reinforcing behaviors and addictive substances, with implications for the development of problem use.

  20. Order of age at onset for substance use, substance use disorder, conduct disorder and psychiatric illness

    DEFF Research Database (Denmark)

    Guldager, Steen; Linneberg, Inger Holm; Hesse, Morten

    2012-01-01

    and social phobia. Of patients reporting an age at onset for SUD and conduct disorder, 84% reported that age at onset was earliest for conduct disorder. Of patients reporting an age at onset for both any non-substance related axis I disorder and any substance related disorder, age at onset was earliest...

  1. Attitude and Peer Influences on Adolescent Substance Use: The Moderating Effect of Age, Sex, and Substance.

    Science.gov (United States)

    Musher-Eizenman, Dara R.; Holub, Shayla C.; Arnett, Mitzi

    2003-01-01

    Examines the importance of peer influence and personal attitudes in relation to self-reported use of alcohol, cigarettes, and marijuana for 213 younger adolescents and 219 older adolescents. Friends' use was significantly related to substance use for both age groups, both sexes, and all substances examined. Resistance self- efficacy was…

  2. An integral approach to substance abuse.

    Science.gov (United States)

    Amodia, Diana S; Cano, Carol; Eliason, Michele J

    2005-12-01

    There is a pressing need in the substance abuse field for more comprehensive models of etiology and treatment that address the complex issues of addiction, including the biological, social, cultural, spiritual and developmental needs of individuals and groups. This article presents a theoretical framework for an integral approach to substance abuse that expands on the existing biopsychosocial model. One contribution of the model is an integrated approach to spirituality from a cross-cultural perspective. This integral approach examines substance abuse etiology and treatment from a four-quadrant perspective adapted from the work of Ken Wilber, and incorporates concepts from integrative medicine and transpersonal psychology/psychiatry. Implications of the model are explored.

  3. Sociocultural perspective of substance use in India.

    Science.gov (United States)

    Sharma, H K

    1996-01-01

    The present communication focuses on a sociocultural perspective of substance use in a pluralistic and diverse culture. India has a history of use of plant products, viz., cannabis, opium, and home-brewed alcoholic beverages, within a defined sociocultural framework over five millennium. Cross sectional epidemiological studies in the field of substance use in different parts of India show that certain social groups are more "vulnerable" to substance use. Caste, religion, and local customs and traditions play a significant role in the choice of drugs, their consumption, and their control in rural/semiurban populations. The intercultural barriers are diminishing in urban populations, and even alien drugs like heroin have been introduced. The social and cultural implications of the traditional vis-a-vis the altering drug use scene are discussed at length.

  4. Occupational turnover intentions among substance abuse counselors.

    Science.gov (United States)

    Rothrauff, Tanja C; Abraham, Amanda J; Bride, Brian E; Roman, Paul M

    2011-01-01

    This study examined predictor, moderator, and mediator variables of occupational turnover intention (OcTI) among substance abuse counselors. Data were obtained via questionnaires from 929 counselors working in 225 private substance abuse treatment (SAT) programs across the United States. Hierarchical multiple regression models were conducted to assess predictor, moderator, and mediator variables of OcTI. OcTI scores were relatively low on a 7-point scale, indicating that very few counselors definitely intended to leave the SAT field. Age, certification, positive perceptions of procedural and distributive justice, and hospital-based status negatively predicted OcTI. Counselors' substance use disorder-impacted history moderated the association between organizational commitment and OcTI. Organizational turnover intention partially mediated the link between organizational commitment and OcTI. Workforce stability might be achieved by promoting perceptions of advantages to working in a particular treatment program, having organizational commitment, showing appreciation for counselors' work, and valuing employees from diverse backgrounds.

  5. Biologically active substances of stone crop fruits

    Directory of Open Access Journals (Sweden)

    Margarita Makarkina

    2014-04-01

    Full Text Available Stone fruit crops are successfully cultivated in many regions of Russia. Their fruits contain a great diversity of biologically active and mineral substances. The stone fruit varietal collection of the All Russia Research Institute of Fruit Crop Breeding has been estimated on the content of biologically active substances (ascorbic acid and phenolic compounds in fruits: 80 sour cherry varieties, 28 sweet cherry varieties, 29 plum varieties and 24 apricot varieties. High cultivar variability of the content of ascorbic acid and P-active sub-stances in fruits has been determined in each crop. The best genotypes have been singled out according to each biochemical component and a complex of characters.

  6. Problems of substance abuse: exploitation and control.

    Science.gov (United States)

    Ray, L

    1985-01-01

    The notion of substance abuse is highly problematic. There is considerable disagreement amongst 'experts' as to the relative hazards and addictive properties of both legally and illegally available substances. There are also widely divergent sub-cultural attitudes to the harmfulness or benefit of drug use. One can assume no social consensus as to the nature of the contemporary 'drug problem', nor about the most appropriate means of dealing with it. There is, however, considerable evidence that criminalization of drug use, and harsh penalties against users and suppliers, are ineffective and counter-productive. Other models of control need to be considered, and in particular the merits and de-merits of the medicalization of drug abuse require examination. However, this is only one aspect of the problem. On the other side are the national and international corporations and syndicates, both legitimate and criminal, that earn vast profits from trade in toxic substances. Tobacco is legally available in every country in the world, and the industry is rarely subject to strict control. Thus the issue of substance abuse and control should be seen in a global context, in which account is taken of both legitimate and underworld operations. In attempts to control international trade in toxic substances, the limited success and the problems of already existing legal controls should be acknowledged. Local awareness and regulation of trade in substances is essential, but not sufficient. Amongst other avenues to be explored is the possibility of diverting presently illicitly grown narcotics into indigenous pharmaceutical industries in the Third World. Some problems with this strategy are noted.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 76 FR 36557 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2011-06-22

    ... Abuse and Mental Health Services, Administration's Center for Substance Abuse Prevention Drug Testing... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse......

  8. Leaf-closing substance in Leucaena leucocephala.

    Science.gov (United States)

    Sohtome, Yoshihiro; Tokunaga, Takashi; Ueda, Katsuhiro; Yamamura, Shosuke; Ueda, Minoru

    2002-01-01

    Potassium (2R,3R)-2,3,4-trihydroxy-2-methylbutanoate (1) was identified as a leaf-closing substance in the nyctinastic plant, Leucaena leucocephala. Compound 1 showed strong leaf-closing activity toward L. leucocephala and was not effective against other nyctinastic plants. The potassium ion was indispensable for the bioactivity of 1. Compound 1 gradually lost its bioactivity because of the exchange of the counter cation during isolation. A leaf-opening substance was also observed in the same plant.

  9. Terahertz spectroscopic investigations of hazardous substances

    Science.gov (United States)

    Bojan, M.; Damian, V.; Fleaca, C.; Vasile, T.

    2016-12-01

    In this paper we report spectral measurements of some relatively common substances but from the hazardous category (possibly to be used like explosives or their manipulation is dangerous) in view to create a database with spectra of such substances. THz transmission spectra of some pure materials and mixed ones are also introduced. The measurements were performed using a Time-Domain system that work in the range of 0.2-4.5 THz. We develop our algorithm to obtain maximum information from the measurement and to minimize the errors.

  10. Substance misuse prevention as corporate social responsibility.

    Science.gov (United States)

    Radacsi, Gergely; Hardi, Peter

    2014-03-01

    All sectors of society should be involved in reducing substance misuse, including businesses. However, the business sector is typically involved only to the extent that their products compel them to be (e.g., alcohol producers promoting responsible alcohol consumption). This article examines why business participation has been limited and how embedding prevention within a framework of health promotion could increase participation. It reviews both Hungarian and international cases, concluding that although corporate social responsibility (CSR) offers a framework to approach substance misuse reduction, a different perception of the role of the business sector is necessary to make it viable.

  11. Playing Video Games While Using or Feeling the Effects of Substances: Associations with Substance Use Problems

    Directory of Open Access Journals (Sweden)

    Geoffrey L. Ream

    2011-10-01

    Full Text Available This study tested the hypothesis that playing video games while using or feeling the effects of a substance—referred to herein as “concurrent use”—is related to substance use problems after controlling for substance use frequency, video gaming as an enthusiastic hobby, and demographic factors. Data were drawn from a nationally representative online survey of adult video gamers conducted by Knowledge Networks, valid n = 2,885. Problem video game playing behavior was operationalized using Tejeiro Salguero and Bersabé Morán’s 2002 problem video game play (PVP measure, and measures for substance use problems were taken from the National Survey of Drug Use and Health (NSDUH. Separate structural equation modeling analyses were conducted for users of caffeine, tobacco, alcohol, and marijuana. In all four models, concurrent use was directly associated with substance use problems, but not with PVP. Video gaming as an enthusiastic hobby was associated with substance use problems via two indirect paths: through PVP for all substances, and through concurrent use for caffeine, tobacco, and alcohol only. Results illustrate the potential for “drug interaction” between self-reinforcing behaviors and addictive substances, with implications for the development of problem use.

  12. Ecotoxicological Hazard Assessment of Genotoxic Substances

    NARCIS (Netherlands)

    Roex EWM; Traas TP; Slooff W; CSR

    2001-01-01

    The current knowledge about the ecological relevance of mutagenic substances is described. Mutations can be divided in somatic and germ-line mutations. Current screening methods in genotoxicology are focussed on the protection of man, and therefore somatic mutations are the most crucial. In the fiel

  13. Substance abuse in victims of fire.

    Science.gov (United States)

    Barillo, D J; Goode, R

    1996-01-01

    Ethanol or drug use may increase the risk of fire-related injury or death. This study was performed to quantify the role of substance abuse in fatal fires occurring in New Jersey over a 7-year period. Records of all the fatalities of fire reported to the State Medical Examiners Office between 1985 and 1991 were retrospectively examined. Blood assay results for ethanol were positive in 215 of the 727 (29.5%) fatalities of fire tested. For this group, the mean blood-ethanol level was 193.9 mg/dl. Blood or urine assay results for substances of abuse were positive in 78 of the 534 (14.6%) fatalities tested. The most commonly detected illicit substances were cocaine, benzodiazepines, barbiturates, and cannabinoids. The test results were positive for both ethanol and drug use in 36 victims. Forty percent of all the fatalities of fire were aged younger than 11 or older than 70. In contradistinction, 75% of drug-positive fatalities of fire and 58% of ethanol-positive fatalities of fire were between the ages of 21 and 50, suggesting that inebriation may impair the ability to escape from fire. Substance abusers in middle life are a previously unrecognized group at higher risk of injury or death in a fire.

  14. Addressing Trauma in Substance Abuse Treatment

    Science.gov (United States)

    Giordano, Amanda L.; Prosek, Elizabeth A.; Stamman, Julia; Callahan, Molly M.; Loseu, Sahar; Bevly, Cynthia M.; Cross, Kaitlin; Woehler, Elliott S.; Calzada, Richard-Michael R.; Chadwell, Katie

    2016-01-01

    Trauma is prevalent among clients with substance abuse issues, yet addictions counselors' training in trauma approaches is limited. The purpose of the current article is to provide pertinent information regarding trauma treatment including the use of assessments, empirically supported clinical approaches, self-help groups and the risk of vicarious…

  15. Substance use disorders in forensic psychiatric patients

    NARCIS (Netherlands)

    Kraan, J.; Verkes, R.J.; Goethals, K.; Vissers, A.; Brazil, I.A.; Bulten, B.H.

    2014-01-01

    There is a lack of detailed information on the role of substance use disorders (SUD) as a substantial factor in offences and treatment in forensic psychiatric patients. The aim of this study was to get a better understanding of these specifics. Clinical records of 193 male patients admitted to a Dut

  16. Binding of cationic surfactants to humic substances

    NARCIS (Netherlands)

    Ishiguro, M.; Tan, W.; Koopal, L.K.

    2007-01-01

    Commercial surfactants are introduced into the environment either through waste products or site-specific contamination. The amphiphilic nature of both surfactants and humic substances (HS) leads to their mutual attraction especially when surfactant and HS are oppositely charged. Binding of the cati

  17. Lichen substances prevent lichens from nutrient deficiency.

    Science.gov (United States)

    Hauck, Markus; Willenbruch, Karen; Leuschner, Christoph

    2009-01-01

    The dibenzofuran usnic acid, a widespread cortical secondary metabolite produced by lichen-forming fungi, was shown to promote the intracellular uptake of Cu(2+) in two epiphytic lichens, Evernia mesomorpha and Ramalina menziesii, from acidic, nutrient-poor bark. Higher Cu(2+) uptake in the former, which produces the depside divaricatic acid in addition to usnic acid, suggests that this depside promotes Cu(2+) uptake. Since Cu(2+) is one of the rarest micronutrients, promotion of Cu(2+) uptake by lichen substances may be crucial for the studied lichens to survive in their nutrient-poor habitats. In contrast, study of the uptake of other metals in E. mesomorpha revealed that the intracellular uptake of Mn(2+), which regularly exceeds potentially toxic concentrations in leachates of acidic tree bark, was partially inhibited by the lichen substances produced by this species. Inhibition of Mn(2+) uptake by lichen substances previously has been demonstrated in lichens. The uptake of Fe(2+), Fe(3+), Mg(2+), and Zn(2+), which fail to reach toxic concentrations in acidic bark at unpolluted sites, although they are more common than Cu(2+), was not affected by lichen substances of E. mesomorpha.

  18. Attaching substances to micro-organisms

    NARCIS (Netherlands)

    Buist, Girbe; Leenhouts, Cornelis Johannes; Venema, Gerard; Kok, Jan

    1999-01-01

    The invention relates to surface display of proteins on micro-organisms via the targeting and anchoring of heterologous proteins to the outer surface of cells such as yeast, fungi, mammalian and plant cells, and bacteria. The invention provides a proteinaceous substance comprising a reactive group a

  19. Reaction between drug substances and pharmaceutical excipients

    DEFF Research Database (Denmark)

    Larsen, Jesper; Cornett, Claus; Jaroszewski, Jerzy Witold;

    2009-01-01

    The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR ...

  20. Neuronal signal substances as biomarkers of migraine

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2006-01-01

    Of the sensory nervous system associated signal substances it is only calcitonin generelated peptide (CGRP) that is reliably associated with the degree of pain in the acute attacks of primary headaches. The treatment with triptans alleviates both the pain and the associated CGRP release, putative...

  1. Study of humic substances by fluorescence spectroscopy

    Directory of Open Access Journals (Sweden)

    Sona Konecna

    2010-12-01

    Full Text Available The purpose of this study is to determine main fluorophores of soil humic substances using 2D and 3D synchronous fluorescencespectroscopy (SFS. The measured synchronous spectra werecompared with standards IHSS. Differences between humic andfulvic acids as well as our and IHSS samples are discussed.

  2. Substance Abuse Taxes the American Workplace

    Science.gov (United States)

    ... are three times higher than for other workers. Workers in recovery from substance abuse have lower turnover rates and are less likely to miss work days, less likely to be hospitalized and have ... hire qualified workers (93 percent) and the costs of worker's compensation ( ...

  3. A cytotoxic substance from Sangre de Grado.

    Science.gov (United States)

    Itokawa, H; Ichihara, Y; Mochizuki, M; Enomori, T; Morita, H; Shirota, O; Inamatsu, M; Takeya, K

    1991-04-01

    Taspine has been isolated as a cytotoxic substance from Sangre de Grado, sap of Croton palanostigma (Euphorbiaceae), by bioassay guided fractionation. The cytotoxicity (IC50) of taspine was found to be 0.39 microgram/ml against KB cells and 0.17 microgram/ml against V-79 cells.

  4. On the nature of humic substances

    Science.gov (United States)

    Fedotov, G. N.; Shoba, S. A.

    2015-12-01

    It is argued that the isolation of low-molecular-weight compounds from humic substances does not prove their supramolecular nature, because small molecules can be sorbed on macromolecules by interacting with them due to noncovalent bonds. The relative mobility of molecular segments in humic substances has been proposed to be used as a criterion for the discrimination between the humic substances of supraand macromolecular nature. The macromolecules are characterized by mobility of their segments, whereas supramolecular systems have stiff structure. This difference between macroand supramolecules results in different behaviors of the matrices (gels) formed from them in the processes of segregation. In the macromolecules, the formations of a new phase appearing at the segregation (microphase separation) are of nano size, at least in one dimension. They are incapable of moving within the matrix and form a well-known, limited set of systems. In the supramolecular matrices, the new-phase formations should have higher mobility and ability to move within the matrix with the formation of particles and zones of not only nano, but also micro sizes, as well as a significantly larger set of systems, including fractal configurations. The experimental electron microscopic study of the humic matrices of soil gels shows that the new-phase formations in the matrix of humic substances have not only nano, but also micro sizes and are capable of moving within the matrix, which confirms the supramolecular nature of humic substances. The proposed method has allowed generalizing the supraand macromolecular approaches, because macromolecules can enter into the composition of supramolecular systems. It is no less important that the behavior of HSs can be perceived as the behavior of stiff impenetrable particles that may compose the structures of different types and sizes.

  5. Incest and substance abuse: implications for treatment professionals.

    Science.gov (United States)

    Janikowski, T P; Glover, N M

    1994-01-01

    Seventy-seven volunteer participants enrolled in eight substance abuse treatment facilities were surveyed using the Substance Abuse and Incest Survey. Of the sample, 36 (48%) reported histories of incest. For participants reporting incest, data on substance abuse history, perceptions of the relationship between incest and substance abuse, and opinions regarding incest-related counseling in the context of substance abuse treatment are presented. Recommendations for substance abuse professionals and facilities are made, including intake screening, barriers to treatment, counselor education, and future research.

  6. Descending mediastinitis managed by sternotomy, taurolidine and delayed closure.

    Science.gov (United States)

    Iyer, Anand P; Kugathasan, Gana; Prabha, Ramesh; Malik, Paras; Kuteyi, Opeyemi; Larbalestier, Robert

    2013-10-01

    Descending necrotizing mediastinitis is a rare complication of upper respiratory infections. A quick diagnosis and prompt and complete surgical drainage is important for a successful outcome. A 74-year-old man with descending necrotizing mediastinitis needed a sternotomy, multiple washouts, and delayed sternal closure.

  7. Psychopathology in Substance Use Disorder Patients with and without Substance-Induced Psychosis

    Directory of Open Access Journals (Sweden)

    Simon Zhornitsky

    2015-01-01

    Full Text Available Background. Substance-induced psychotic disorder (SIPD is a diagnosis constructed to distinguish substance-induced psychotic states from primary psychotic disorders. A number of studies have compared SIPD persons with primary psychotic patients, but there is little data on what differentiates substance use disorder (SUD individuals with and without SIPD. Here, we compared psychopathology, sociodemographic variables, and substance use characteristics between SUD patients with and without SIPD. Methods. A retrospective chart review was conducted on newly admitted patients at a rehabilitation centre between 2007 and 2012. Results. Of the 379 patients included in the study, 5% were diagnosed with SIPD n=19 and 95% were diagnosed with SUDs without SIPD n=360. More SIPD patients reported using cannabis and psychostimulants, and fewer SIPD patients reported using alcohol than SUDs patients without SIPD. SIPD patients scored higher on the “schizophrenia nuclear symptoms” dimension of the SCL-90R psychoticism scale and exhibited more ClusterB personality traits than SUD patients without SIPD. Discussion. These data are consistent with previous studies suggesting that psychopathology, substance type, and sociodemographic variables play important role in the development of SIPD. More importantly, the results highlight the need for paying greater attention to the types of self-reported psychotic symptoms during the assessment of psychotomimetic effects associated with psychoactive substances.

  8. Substance Abuse and Prison Recidivism: Themes from Qualitative Interviews

    Science.gov (United States)

    Phillips, Lindsay A.

    2010-01-01

    This qualitative analysis explores the role of substance abuse in reentry from prison to society. Participants who recidivated (N = 20) in an urban prison system identified substance abuse as their primary reason for recidivism. Treatment implications are discussed.

  9. 76 FR 21915 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-04-19

    ... substance to manufacture bulk controlled substance for distribution to its customer. As explained in the.... 823(a), and 21 CFR 1301.34(b), (c), (d), (e), and (f) are satisfied. Dated: April 11, 2011. Joseph...

  10. Sampling Odor Substances by Mist-Cyclone System

    Science.gov (United States)

    Matsubara, Osamu; Jiang, Zhiheng; Toyama, Shigeki

    2009-05-01

    Many techniques have been developed to measure odor substances. However most of those methods are based on using aquatic solutions(1),(2). Many odor substances specifically at low density situation, are difficult to dissolve into water. To absorb odor substances and obtain highest concentration solutions are key problems for olfactory systems. By blowing odor substances contained air mixture through mist of water and then separating the liquid from two-phases fluid with a cyclone unit a high concentration solution was obtained.

  11. Addiction: Alcohol and Substance Abuse in Judaism

    Directory of Open Access Journals (Sweden)

    Kate Miriam Loewenthal

    2014-09-01

    Full Text Available This article outlines a history of rulings and beliefs about addiction in Judaism, covering alcohol and substance use and addiction, in the context of a brief account of the development of the status of addiction. It examines the prevalence of alcohol and substance use and abuse among Jews, including a discussion of some of the difficulties in estimating prevalence and of factors involved in changing patterns of use and abuse. Community beliefs and attitudes are examined, using published material and interviews with community leaders and members. Some conclusions are suggested about the impact of religious rulings and of other factors on addiction among Jews. Attention is given to the phenomenon of denial. Therapeutic practices and organisations are described. The scope for further research is identified.

  12. [Antihypoxic properties of opiates and substance P].

    Science.gov (United States)

    Vlasova, I G; Torshin, V I

    2001-01-01

    Using survival slices of the rat cerebellum, we studied the influence of opiates (alpha- and beta-endorphines, met-enkephalines) as well as substance P (SP) on the impulse activity (IA) of neurons. Low doses of the studied substances (10(-8)-10(-10) M) for the most part increased the IA of the neurons, while high doses (10(6)-10(-5) M) produced biphasic reaction (inhibition-excitation). It is supposed that opiates and SP act as transmitters in the cerebellum. Under increasing hypoxia, opiates and SP manifested antixypoxic properties both in low O22 concentration and under reoxygenation. Opiates and SP proved to be natural antihypoxants involved not only in nociception mechanisms but also in brain adaptation to oxygen deficiency.

  13. Borderline personality and substance use in women.

    Science.gov (United States)

    Feske, Ulrike; Tarter, Ralph E; Kirisci, Levent; Pilkonis, Paul A

    2006-01-01

    The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD.

  14. [The substance experience, a history of LSD].

    Science.gov (United States)

    Beck, François; Bonnet, Nicolas

    2013-04-01

    This article reviews the recent knowledge on LSD stemming from various disciplines among which pharmacology, sociology and epidemiology. The d-lysergic acid diethylamide (LSD) is a particularly powerful hallucinogenic substance. It produces distortions and hearing, visual and tactile hallucinations. Rarely used (only 1.7% of people aged 15-64 years old have tried it in their lifetime), this very powerful drug generates a strong apprehension within the general population, but the ethnographical studies show that its image seems rather good among illicit drug users. This representation relies both on the proper effects of this substance and also on the history of LSD very closely linked to the counterculture characteristic of the years 1960-1970.

  15. Substance dependency among homeless American Indians.

    Science.gov (United States)

    Lobo, Susan; Vaughan, Margaret Mortensen

    2003-01-01

    Extensive qualitative research in the San Francisco Bay Area in California and in Tucson, Arizona, indicates strong associations between substance abuse and homelessness among American Indians. This article takes a comparative approach to describe and analyze precipitating factors and survival patterns of those who are both homeless and who suffer from substance dependency. Possible precipitating factors presented through case studies consider the complex interaction of childhood fostering or adoption into non-Native families, different types of involuntary institutionalization during youth, and the personal impact of accident, trauma and loss. Coping strategies and keys to survival are examined, including the role of the extended family and close friendships, American Indian and mainstream organizations that offer formal and informal services, the existence of anchor or key households, the helping relationships and sobriety groups among homeless individuals, spirituality, and cultural resiliency.

  16. The Link: Trauma and Substance Abuse

    Directory of Open Access Journals (Sweden)

    Leslie Dawn Culpepper

    2016-03-01

    Full Text Available Trauma “is categorized as an overwhelming life-changing experience (and is typically a physical and/or emotional shock to the very fiber of one’s being.”It is a priority that those who experience trauma in their lives seek help from a licensed professional to deal with the emotional damage caused by the trauma(s and to be taught necessary coping skills to prevent them from seeking solace in unhealthy ways like abusing drugs and/or alcohol. Research proposes that all types of trauma and the aftermath that follows will likely impact the “exposed population’s behavioral health, resulting in an increase in mental and substance use disorders, along with a decline in perceived quality of life” [1]. Survey results teach us that more than 70% adolescents receiving treatment for substance abuse across the country have a history of trauma in their lives.

  17. [Consumption of psychoactive substances by caregivers].

    Science.gov (United States)

    Gauthier, Françoise

    2012-11-01

    Prescribed medication, self-medication or doping the use of psychoactive substances by caregivers is varied. Doping behaviour in the care environment is under-estimated and trivialised. It is often difficult to spot at an early stage and yet this consumption is not without consequences on the quality and safety of work. Gérard-Marchant general hospital in Toulouse integrates this issue into its professional risk management policy.

  18. Pulmonary complications of smoked substance abuse.

    OpenAIRE

    Tashkin, D. P.

    1990-01-01

    After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cell...

  19. Genetic and perinatal effects of abused substances

    Energy Technology Data Exchange (ETDEWEB)

    Brande, M.C.; Zimmerman, A.M.

    1987-01-01

    This book provides an overview of the effects of several abused drugs, including opiates, cannabinoids, alcohol, nicotine, and cocaine, with special emphasis on the actions of these substances at the molecular and cellular levels. The first half deals with genetic effects, including molecular genetics, biochemical genetics, pharmacogenetics, cytogenetics, and genetic toxicity. The second half focuses on perinatal effects and covers: drug abuse during pregnancy; biochemical aspects of marihuana on male reproduction; and long-term behavioral and neuroendocrine effects of perinatal alcohol exposure.

  20. Developmental Trajectories of Adolescent Substance Use

    Science.gov (United States)

    Yamada, Samantha; Pepler, Debra; Jiang, Depeng; Cappadocia, M. Catherine; Craig, Wendy; Connolly, Jennifer

    2016-01-01

    Longitudinal data from 746 adolescents in Toronto, Canada (54% females), was gathered in eight waves over seven years (1995 through 2001), beginning when the youths were 10 to 12 years old (mean age = 11.8, SD = 1.2 years). Five trajectories of substance use were identified: chronic-high, childhood onset-rapid high, childhood onset-moderate,…

  1. Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress

    Directory of Open Access Journals (Sweden)

    Yeh Chi-Chen

    2012-08-01

    Full Text Available Abstract Background Methanolic extracts of Gracilaria tenuistipitata (MEGT were obtained from the edible red algae. Previously, we found that water extract of G. tenuistipitata was able to modulate oxidative stress-induced DNA damage and its related cellular responses. Methods In this study, the methanol extraction product MEGT was used to evaluate the cell growth inhibition in oral cancer cells and its possible mechanism was investigated. Results The cell viability of MEGT treated Ca9-22 oral cancer cell line was significantly decreased in a dose–response manner (p p p p p 2(3 intensity for mitochondrial membrane potential (MMP of MEGT-treated Ca9-22 cancer cells was significantly decreased in a dose–response manner (p  Conclusions These results indicated that MEGT had apoptosis-based cytotoxicity against oral cancer cells through the DNA damage, ROS induction, and mitochondrial depolarization. Therefore, MEGT derived from the edible algae may have potential therapeutic effects against oral squamous cell carcinoma (OSCC.

  2. Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine.

    Science.gov (United States)

    Dziedzic, Arkadiusz; Kubina, Robert; Bułdak, Rafał J; Skonieczna, Magda; Cholewa, Krzysztof

    2016-03-17

    The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs.

  3. Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

    Directory of Open Access Journals (Sweden)

    Arkadiusz Dziedzic

    2016-03-01

    Full Text Available The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628, cultivated with the mixture of Dulbecco's modified Eagle’s medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50 after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs.

  4. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

    NARCIS (Netherlands)

    Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

    2011-01-01

    Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

  5. The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs

    DEFF Research Database (Denmark)

    Jensen, Mette; Groth, L.; Holmer, G.;

    2002-01-01

    The objective of this study was to establish essential fatty acid deficiency (EFAD) in hairless rats and investigate the potential of this model as a psoriasis screening model by testing the effects of calcipotriol and dithranol on differentiation and proliferation in the epidermis. Hairless rats...... were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms......, histology of the epidermis and fatty acid analysis of serum and skin. Immediately after the EFAD condition had been established, the animals were treated with dithranol ointment or different concentrations of calcipotriol solution. A reduction in epidermal thickness of 15-20% was seen after the treatment...

  6. Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells

    Science.gov (United States)

    Hivelin, Mikael; Nusbaum, Patrick; Hubas, Arnaud; Laurendeau, Ingrid; Lantieri, Laurent; Wolkenstein, Pierre; Vidaud, Michel; Pasmant, Eric; Chapuis, Nicolas; Parfait, Béatrice

    2016-01-01

    Approximately 30-50% of individuals with Neurofibromatosis type 1 develop benign peripheral nerve sheath tumors, called plexiform neurofibromas (PNFs). PNFs can undergo malignant transformation to highly metastatic malignant peripheral nerve sheath tumors (MPNSTs) in 5-10% of NF1 patients, with poor prognosis. No effective systemic therapy is currently available for unresectable tumors. In tumors, the NF1 gene deficiency leads to Ras hyperactivation causing the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and inducing multiple cellular responses including cell proliferation. In this study, three NF1-null MPNST-derived cell lines (90-8, 88-14 and 96-2), STS26T sporadic MPNST cell line and PNF-derived primary Schwann cells were used to test responses to AZD8055, an ATP-competitive “active-site” mTOR inhibitor. In contrast to rapamycin treatment which only partially affected mTORC1 signaling, AZD8055 induced a strong inhibition of mTORC1 and mTORC2 signaling in MPNST-derived cell lines and PNF-derived Schwann cells. AZD8055 induced full blockade of mTORC1 leading to an efficient decrease of global protein synthesis. A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST-derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. Cell migration was impaired by AZD8055 treatment and cell cycle analysis showed a G0/G1 arrest. Combined effects of AZD8055 and PD0325901 MEK inhibitor as well as BRD4 (BromoDomain-containing protein 4) inhibitors showed a synergistic antiproliferative effect. These data suggest that NF1-associated peripheral nerve sheath tumors are an ideal target for AZD8055 as a single molecule or in combined therapies. PMID:26840085

  7. Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals

    DEFF Research Database (Denmark)

    Wu, Xudong; Bekker-Jensen, Ida Holst; Christensen, Jesper;

    2015-01-01

    ASXL1 mutations are frequently found in hematological tumors, and loss of Asxl1 promotes myeloid transformation in mice. Here we present data supporting a role for an ASXL1-BAP1 complex in the deubiquitylation of mono-ubiquitylated lysine 119 on Histone H2A (H2AK119ub1) in vivo. The Polycomb grou...

  8. Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells.

    Science.gov (United States)

    Varin, Jennifer; Poulain, Laury; Hivelin, Mikael; Nusbaum, Patrick; Hubas, Arnaud; Laurendeau, Ingrid; Lantieri, Laurent; Wolkenstein, Pierre; Vidaud, Michel; Pasmant, Eric; Chapuis, Nicolas; Parfait, Béatrice

    2016-06-14

    Approximately 30-50% of individuals with Neurofibromatosis type 1 develop benign peripheral nerve sheath tumors, called plexiform neurofibromas (PNFs). PNFs can undergo malignant transformation to highly metastatic malignant peripheral nerve sheath tumors (MPNSTs) in 5-10% of NF1 patients, with poor prognosis. No effective systemic therapy is currently available for unresectable tumors. In tumors, the NF1 gene deficiency leads to Ras hyperactivation causing the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and inducing multiple cellular responses including cell proliferation. In this study, three NF1-null MPNST-derived cell lines (90-8, 88-14 and 96-2), STS26T sporadic MPNST cell line and PNF-derived primary Schwann cells were used to test responses to AZD8055, an ATP-competitive "active-site" mTOR inhibitor. In contrast to rapamycin treatment which only partially affected mTORC1 signaling, AZD8055 induced a strong inhibition of mTORC1 and mTORC2 signaling in MPNST-derived cell lines and PNF-derived Schwann cells. AZD8055 induced full blockade of mTORC1 leading to an efficient decrease of global protein synthesis. A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST-derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. Cell migration was impaired by AZD8055 treatment and cell cycle analysis showed a G0/G1 arrest. Combined effects of AZD8055 and PD0325901 MEK inhibitor as well as BRD4 (BromoDomain-containing protein 4) inhibitors showed a synergistic antiproliferative effect. These data suggest that NF1-associated peripheral nerve sheath tumors are an ideal target for AZD8055 as a single molecule or in combined therapies.

  9. Anti-proliferative effects of Salacia reticulata leaves hot-water extract on interleukin-1β-activated cells derived from the synovium of rheumatoid arthritis model mice

    Directory of Open Access Journals (Sweden)

    Sekiguchi Yuusuke

    2012-04-01

    Full Text Available Abstract Background Salacia reticulata (SR is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL to inhibit in vitro the interleukin-1β (IL-1β-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice. Findings Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC, liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE, and protease digestion. The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 μg/mL. Treatment with a low dose (25 μg dry matter per millilitre of the extract inhibited IL-1β-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1β-activated cell proliferation. Conclusions We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1β-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins.

  10. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion Collectively our data provides evidence that Chmp1A mediates the growth inhibitory activity of ATRA in human pancreatic cancer cells via regulation of CRBP-1. Our results also suggest that nuclear localization of Chmp1A is important in mediating ATRA signaling.

  11. New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549.

    Science.gov (United States)

    Gao, Tian-yang; Jin, Xing; Tang, Wen-zhao; Wang, Xiao-jing; Zhao, Yun-xue

    2015-09-01

    Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells.

  12. In vitro evaluation of the anti-proliferative activities of the wood essential oils of three Cedrus species against K562 human chronic myelogenous leukaemia cells.

    Science.gov (United States)

    Saab, Antoine M; Lampronti, Ilaria; Borgatti, Monica; Finotti, Alessia; Harb, Faouzi; Safi, Samir; Gambari, Roberto

    2012-01-01

    There are four kinds of Cedar: Cedrus libani naturally occurring in Lebanon, Syria and Turkey, Cedrus atlantica in Morocco and Algeria, Cedrus brevefolia in Cyprus Island and Cedrus deodara which is distributed in Himalayan Mountains. Wood essential oils obtained from C. libani, C. atlantica and C. deodara were tested for the inhibition of K562 cell proliferation and for the induction of erythroid differentiation. The wood essential oils of C. libani, C. atlantica and C. deodara inhibited the proliferation of the K562 cell line exhibiting IC(50) values 23.38 ± 1.7, 59.37 ± 2.6 and 37.09 ± 1.4 µg mL(-1), respectively. Meanwhile, C. libani wood oils induced a percentage of erythroid differentiation of 15 ± 2% at concentration 5 µg mL(-1). Cedrus deodara wood oil indicated a percentage of erythroid differentiation of 20 ± 2% at concentration 25 µg mL(-1) and C. atlantica wood oils showed a percentage of erythroid differentiation of 12 ± 1.8% at concentration 10 µg mL(-1).

  13. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.

    Science.gov (United States)

    Zhang, Sheng; Li, Feng; Younes, Mamoun; Liu, Hao; Chen, Changyi; Yao, Qizhi

    2013-01-01

    Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1). However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+) breast cancer patients was significantly associated with poor survival (pcancer. 17-β estradiol (E2) treatment of high SELENBP1-expressing ER(+) cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(-) cell lines. However, after ectopic expression of ER in an originally ER(-) cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression as a potential biomarker in contributing to breast cancer prevention and treatment.

  14. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    Full Text Available Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1. However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+ breast cancer patients was significantly associated with poor survival (p<0.01, and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2 treatment of high SELENBP1-expressing ER(+ cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(- cell lines. However, after ectopic expression of ER in an originally ER(- cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression as a potential biomarker in contributing to breast cancer prevention and treatment.

  15. Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms.

    Science.gov (United States)

    Chen, Hong-Sheng; Liu, Yan; Lin, Luo-Qiang; Zhao, Jin-Lu; Zhang, Chun-Peng; Jin, Jun-Chao; Wang, Lei; Bai, Ming-Han; Wang, Yi-Chong; Liu, Ming; Shen, Bao-Zhong

    2011-01-01

    The root of Polygonum multiflorum Thunb. (PM) is utilized to treat many diseases associated with aging. Research also indicates that PM inhibits the proliferation of certain types of cancer cells. The aim of the present study was to evaluate the inhibitory effect of PM extract (PME) on the proliferation of MCF-7 cells and to investigate the underlying mechanisms. Inhibition of the proliferation of MCF-7 cells was determined by the MTT assay. Cell cycle distribution and apoptotic rates were evaluated by flow cytometry, and cell cycle and apoptosis-related protein expression was assessed by Western blotting. Apoptotic characteristics of MCF-7 cells were detected by transmission electron microscopy. The present study showed that PME at doses of 100, 150, 200 and 250 µg/ml significantly inhibited proliferation of MCF-7 cells in a time- and dose-dependent manner. Flow cytometry showed that the cell apoptotic rates were 9.1 ± 1.67 and 17.7 ± 2.93% after treatment with 100 and 200 µg/ml PME for 48 h, respectively. The proportions of cells in the G2/M phase were 37.9 ± 1.47 and 42.0 ± 1.71% after treatment with 100 and 200 µg/ml PME for 24 h, respectively. Western blot analysis showed that PME down-regulated the protein expression of Cdc25B and Cdc25C phosphatases accompanied by an increase in phospho-Cdk1, and PME promoted cytochrome c release from mitochondria into the cytosol to activate caspase-9. The present study demonstrated that PME inhibited MCF-7 cell proliferation by inducing cell cycle arrest in the G2/M phase and promoting cell apoptosis. The effects of PME on MCF-7 cells were associated with the modulation of the expression levels of proteins involved in the cell cycle and apoptosis. These data suggest that PME has promise as a treatment against breast cancer by inhibiting the proliferation of cancer cells.

  16. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones have enhanced activity under high glucose conditions

    Directory of Open Access Journals (Sweden)

    de Dios Stephanie T

    2007-10-01

    Full Text Available Abstract Background Inhibition of vascular smooth muscle cell (vSMC proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose and high (25 mM glucose increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P 3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations. The sulfonylureas chlorpropamide and gliclazide had no inhibitory effect on vSMC proliferation assessed by either [3H]-thymidine incorporation or cell numbers. Conclusion TZDs but not sulfonylureas nor biguanides (except phenformin at high concentrations show favorable vascular actions assessed as inhibition of vSMC proliferation. The activity of rosiglitazone and pioglitazone is enhanced under high glucose conditions. These data provide further in vitro evidence for the potential efficacy of TZDs in preventing multiple cardiovascular diseases. However, the plethora of potentially beneficial actions of TZDs in cell and animal models have not been reflected in the results of major clinical trials and a greater understanding of these complex drugs is required to delineate their ultimate clinical utility in preventing macrovascular disease in diabetes.

  17. A hemagglutinin from northeast red beans with immunomodulatory activity and anti-proliferative and apoptosis-inducing activities toward tumor cells.

    Science.gov (United States)

    Chan, Yau Sang; Wong, Jack Ho; Fang, Evandro Fei; Pan, Wenliang; Ng, Tzi Bun

    2013-10-01

    A 64-kDa hemagglutinin from a Phaseolus vulgaris cultivar, the northeast red bean, was purified by a protocol composed of three chromatographic steps involving affinity chromatography on Affi-gel blue gel, cation exchange chromatography on SP-Sepharose and FPLC-gel filtration on Superdex 75. The purified hemagglutinin appeared as a single 32-kDa band in SDS-PAGE indicating its dimeric nature. The N-terminal amino acid sequence of the hemagglutinin resembled the sequences of lectins and hemagglutinins from a number of Phaseolus species. The hemagglutinin manifested moderate thermostability and pH stability. It retained full activity up to 65 °C and in the pH range 2-12. It did not interact with simple sugars such as glucose, mannose and galactose. The hemagglutinin exerted immunostimulatory effects by upregulating the expression of cytokines like interferon-γ and tumor necrosis factor-α. It also exhibited antiproliferative activity on a number of tumor cells including MCF7 (breast cancer), HepG2 (liver cancer), CNE1 and CNE2 (nasopharyngeal cancer) cells, with stronger activity toward MCF7 and CNE1 cells. The hemagglutinin induced phophatidylserine externalization, mitochondrial depolarization and DNA condensation in MCF7 cells, indicating initiation of apoptosis. However, at high hemagglutinin concentrations, severe damage to the MCF7 cells was detected.

  18. Brown Kidney Bean Bowman-Birk Trypsin Inhibitor is Heat and pH Stable and Exhibits Anti-proliferative Activity.

    Science.gov (United States)

    Chan, Yau Sang; Zhang, Yanbo; Ng, Tzi Bun

    2013-02-01

    A trypsin inhibitor with a molecular mass around 17 kDa was purified from the seeds of Phaseolus vulgaris cv. 'brown kidney bean'. The purification protocol involved, in sequence, affinity chromatography on Affi-gel blue gel, ion-exchange chromatography on Q-Sepharose and Mono Q, and gel filtration on Superdex 75. The molecular size and N-terminal amino acid sequence of the trypsin inhibitor resembled leguminous Bowman-Birk protease inhibitors (BBIs), signifying that brown kidney bean trypsin inhibitor is a BBI. Brown kidney bean trypsin inhibitor exhibited pronounced thermostability and pH stability. Its trypsin inhibitory activity was retained at all pH values (0-14) and up to 90 °C. The trypsin inhibitor also inhibited the proliferation of human breast cancer MCF7 cells with an IC(50) of 71.52 μM. On the other hand, it only slightly inhibited proliferation of hepatoma HepG2 and embryonic liver WRL68 cells at a concentration over 110 μM.

  19. The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs

    DEFF Research Database (Denmark)

    Jensen, M.; Groth, L.; Fullerton, A.;

    2002-01-01

    , histology of the epidermis and fatty acid analysis of serum and skin. Immediately after the EFAD condition had been established, the animals were treated with dithranol ointment or different concentrations of calcipotriol solution. A reduction in epidermal thickness of 15-20% was seen after the treatment...... with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal...

  20. Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line.

    Science.gov (United States)

    Hoda, Muddasarul; Pajaniradje, Sankar; Shakya, Garima; Mohankumar, Kumaravel; Rajagopalan, Rukkumani

    2016-08-01

    There is an emerging trend to restudy known drugs for their anti-cancer potential. One such anti-alcoholic drug, disulfiram, with significant anti-cancer potential was studied for its efficacy against Hep3B cell lines, an in vitro model of hepatocellular carcinoma. Simultaneously, we intended to study the effect of polysorbate 80-stabilized PLGA nanoparticles and its DSF-loaded counterpart. Cell and nuclear staining, comet assay, flow cytometry and Western blots were performed. Results suggest that cell proliferation was inhibited by DSF and its PLGA nanoparticles through cell cycle arrest, triggering activation of apoptotic pathways that culminates with cell death. DSF loaded nanoparticles when compared with free DSF, showed significantly lesser effect due to its sustained drug-releasing property, while empty nanoparticles showed negligible influence on Hep3B cells. Our results suggest that DSF alone contributes to cell death, while polysorbate 80-stabilized PLGA nanoparticles show sustained drug release patterns that would potentially lower dosage regimens.

  1. Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells.

    Directory of Open Access Journals (Sweden)

    Melchiorre Cervello

    Full Text Available Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC. Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex® is a selective cyclooxygenase-2 (COX-2 inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies.

  2. Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblasts.

    Science.gov (United States)

    Certal, Mariana; Vinhas, Adriana; Pinheiro, Ana Rita; Ferreirinha, Fátima; Barros-Barbosa, Aurora Raquel; Silva, Isabel; Costa, Maria Adelina; Correia-de-Sá, Paulo

    2015-11-01

    During myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated the role UTP on calcium signaling and proliferation of CF cultured from ventricles of adult rats. Co-expression of discoidin domain receptor 2 and α-smooth muscle actin indicate that cultured CF are activated myofibroblasts. Intracellular calcium ([Ca(2+)]i) signals were monitored in cells loaded with Fluo-4 NW. CF proliferation was evaluated by the MTT assay. UTP and the selective P2Y4 agonist, MRS4062, caused a fast desensitizing [Ca(2+)]i rise originated from thapsigargin-sensitive internal stores, which partially declined to a plateau providing the existence of Ca(2+) in the extracellular fluid. The biphasic [Ca(2+)]i response to UTP was attenuated respectively by P2Y4 blockers, like reactive blue-2 and suramin, and by the P2Y11 antagonist, NF340. UTP and the P2Y2 receptor agonist MRS2768 increased, whereas the selective P2Y11 agonist NF546 decreased, CF growth; MRS4062 was ineffective. Blockage of the P2Y11 receptor or its coupling to adenylate cyclase boosted UTP-induced CF proliferation. Confocal microscopy and Western blot analysis confirmed the presence of P2Y2, P2Y4 and P2Y11 receptors. Data indicate that besides P2Y4 and P2Y2 receptors which are responsible for UTP-induced [Ca(2+)]i transients and growth of CF, respectively, synchronous activation of the previously unrecognized P2Y11 receptor may represent an important target for anti-fibrotic intervention in cardiac remodeling.

  3. Anti-proliferative effect of fungal taxol extracted from Cladosporium oxysporum against human pathogenic bacteria and human colon cancer cell line HCT 15

    Science.gov (United States)

    Gokul Raj, K.; Manikandan, R.; Arulvasu, C.; Pandi, M.

    2015-03-01

    Cladosporium oxysporum a new taxol producing endophytic fungus was identified and production of taxol were characterized using UV-visible spectroscopy (UV-vis), high-performance liquid chromatography (HPLC), infrared (IR) nuclear magnetic resonance spectroscopy (NMR (13C and 1H)) and liquid chromatography-mass spectrometry (LC-MS). The taxol biosynthetic gene (dbat) was evaluated for new taxol producing fungus. Antibacterial activity against six different human pathogenic bacteria was done by agar well diffusion method. The anticancer efficacy of isolated fungal taxol were also evaluated in human colon cancer cell HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cytotoxicity and nuclear morphology analysis. The isolated fungal taxol showed positive towards biosynthetic gene (dbat) and effective against both Gram positive as well as Gram negative. The fungal taxol suppress growth of cancer cell line HCT 15 with an IC50 value of 3.5 μM concentration by 24 h treatment. Thus, the result reveals that C. oxysporum could be a potential alternative source for production of taxol and have antibacterial as well as anticancer properties with possible clinical applications.

  4. Synthesis, characterization and anti-proliferative activity of Cd(II) complexes with NNN type pyrazole-based ligand and pseudohalide ligands as coligand

    Science.gov (United States)

    Hopa, Cigdem; Yildirim, Hatice; Kara, Hulya; Kurtaran, Raif; Alkan, Mahir

    2014-03-01

    Cd(II) complexes of tridentate nitrogen donor ligand, 2,6-bis(3,4,5-trimethylpyrazolyl)pyridine (btmpp), Cd(btmpp)X2 (X:Cl, ONO or N(CN)2) have been synthesized and characterized by elemental and spectral (FT-IR, 1H NMR, 13C NMR, UV-Vis) analyses, differential thermal analysis and single crystal X-ray diffraction studies. The molecular structure of reported complex 1, revealed distorted square-pyramidal geometry around Cadmium. Complexes 1-3 and corresponding ligand were tested for cytotoxic activity against the human carcinoma cell lines HEP3B (hepatocellular carcinoma), PC3 (prostate adenocarcinoma), MCF7 (breast adenocarcinoma) and Saos2 (osteosarcoma). The results show that, complexes are more cytotoxic than the free ligand and complex 2 is the most cytotoxic complex for PC3.

  5. Heart rate variability biofeedback in adolescent substance abuse treatment.

    Science.gov (United States)

    Thurstone, Chris; Lajoie, Travis

    2013-01-01

    Strategies are needed to improve adolescent substance abuse treatment outcomes. For example, during outpatient substance abuse treatment, up to 80% of adolescents continue to use.(1),(2) Following residential substance abuse treatment, 88% of adolescents relapse within 6 months.(3.)

  6. 49 CFR 392.4 - Drugs and other substances.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Drugs and other substances. 392.4 Section 392.4... VEHICLES General § 392.4 Drugs and other substances. (a) No driver shall be on duty and possess, be under the influence of, or use, any of the following drugs or other substances: (1) Any 21 CFR...

  7. Attitudes towards Substance Addiction: A Study of Turkish University Students

    Science.gov (United States)

    Sungu, Hilmi

    2015-01-01

    Substance addiction has become one of the important issues in the world. The studies concerning substance use reveal the extent of the problem. According to the results of such studies, the number of the people using illicit drugs has increased profoundly in recent years. In this study, it was tried to find out how common substance use among…

  8. School-Based Interventions for Students with Substance Abuse

    Science.gov (United States)

    Burrow-Sanchez, Jason J.; Jenson, William R.; Clark, Elaine

    2009-01-01

    Experimentation with substances is typical for many young people, but unfortunately some will go on to develop substance abuse problems that substantially affect their lives. Successfully intervening with students who use or abuse substances is a challenge for school mental health professionals across the nation. There is a need for evidence-based…

  9. [Related substances in orlistat detected with UPLC-MS/MS].

    Science.gov (United States)

    Zhang, Ting-Ting; Ma, Chen

    2014-03-01

    The study aims to identify related substances in orlistat pharmaceutical substance from different production technologies. Advanced technologies including UPLC-QTOF-MS and UPLC-QTrap-MS were used and the structures or molecules of 10 kinds of related substances in orlistat were identified. The experimental data were valuable to the quality control and development of orlistat.

  10. 21 CFR 176.130 - Anti-offset substances.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Anti-offset substances. 176.130 Section 176.130... for Use Only as Components of Paper and Paperboard § 176.130 Anti-offset substances. Substances named... in printing and decorating paper and paperboard used for food packaging in accordance with...

  11. 76 FR 53961 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-08-30

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated April... Enforcement Administration (DEA) to be registered as a bulk manufacturer of 4-Anilino-N-phenethyl-4-Piperidine... controlled substance in the manufacturer of another controlled substance. No comments or objections have...

  12. Adolescent Sexual Behaviors at Varying Levels of Substance Use Frequency

    Science.gov (United States)

    Floyd, Leah J.; Latimer, William

    2010-01-01

    Combining substance use and sex compounds the risk of contracting sexually transmitted diseases, including HIV. However, the association between substance use and sexual behaviors may vary by substance and sexual behavior. The current study sought to examine the relationship between alcohol and marijuana use frequency and specific sexual…

  13. Substance Abuse by Youth and Young Adults in Rural America

    Science.gov (United States)

    Lambert, David; Gale, John A.; Hartley, David

    2008-01-01

    Purpose: Addressing substance abuse in rural America requires extending our understanding beyond urban-rural comparisons to how substance abuse varies across rural communities of different sizes. We address this gap by examining substance abuse prevalence across 4 geographic levels, focusing on youth (age 12-17 years) and young adults (age 18-25…

  14. Resilience as a Theoretical Basis for Substance Abuse Prevention.

    Science.gov (United States)

    Meschke, Laurie L.; Patterson, Joan M.

    2003-01-01

    Uses the resilience perspective to examine the risk and protective mechanisms associated with adolescent substance use. Resilience is defined and resilience processes related to substance use are explored. Effective adolescent substance use prevention programs that promote youth resilience are reviewed. (Contains 120 references.) (GCP)

  15. From substance use to homelessness or vice versa?

    NARCIS (Netherlands)

    McVicar, Duncan; Moschion, Julie; van Ours, Jan

    2015-01-01

    Homelessness is associated with substance use, but whether substance use precedes or follows homelessness is unclear. We investigate the nature of the relationship between homelessness and substance use using data from the unique Australian panel dataset Journeys Home collected in 4 surveys over the

  16. Patient registries for substance use disorders

    Directory of Open Access Journals (Sweden)

    Tai B

    2014-07-01

    Full Text Available Betty Tai,1 Lian Hu,2 Udi E Ghitza,1 Steven Sparenborg,1 Paul VanVeldhuisen,2 Robert Lindblad2 1Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA; 2The EMMES Corporation, Rockville, MD, USA Abstract: This commentary discusses the need for developing patient registries of substance use disorders (SUD in general medical settings. A patient registry is a tool that documents the natural history of target diseases. Clinicians and researchers use registries to monitor patient comorbidities, care procedures and processes, and treatment effectiveness for the purpose of improving care quality. Enactments of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity Act 2008 open opportunities for many substance users to receive treatment services in general medical settings. An increased number of patients with a wide spectrum of SUD will initially receive services with a chronic disease management approach in primary care. The establishment of computer-based SUD patient registries can be assisted by wide adoption of electronic health record systems. The linkage of SUD patient registries with electronic health record systems can facilitate the advancement of SUD treatment research efforts and improve patient care. Keywords: substance use disorders, primary care, registry, electronic health records, chronic care model

  17. Medical marijuana users in substance abuse treatment

    Directory of Open Access Journals (Sweden)

    Swartz Ronald

    2010-03-01

    Full Text Available Abstract Background The rise of authorized marijuana use in the U.S. means that many individuals are using cannabis as they concurrently engage in other forms of treatment, such as substance abuse counseling and psychotherapy. Clinical and legal decisions may be influenced by findings that suggest marijuana use during treatment serves as an obstacle to treatment success, compromises treatment integrity, or increases the prevalence or severity of relapse. In this paper, the author reviews the relationship between authorized marijuana use and substance abuse treatment utilizing data from a preliminary pilot study that, for the first time, uses a systematic methodology to collect data examining possible effects on treatment. Methods Data from the California Outcomes Measurement System (CalOMS were compared for medical (authorized marijuana users and non-marijuana users who were admitted to a public substance abuse treatment program in California. Behavioral and social treatment outcomes recorded by clinical staff at discharge and reported to the California Department of Alcohol and Drug Programs were assessed for both groups, which included a sample of 18 reported medical marijuana users. Results While the findings described here are preliminary and very limited due to the small sample size, the study demonstrates that questions about the relationship between medical marijuana use and involvement in drug treatment can be systematically evaluated. In this small sample, cannabis use did not seem to compromise substance abuse treatment amongst the medical marijuana using group, who (based on these preliminary data fared equal to or better than non-medical marijuana users in several important outcome categories (e.g., treatment completion, criminal justice involvement, medical concerns. Conclusions This exploratory study suggests that medical marijuana is consistent with participation in other forms of drug treatment and may not adversely affect

  18. Is It the Music? Peer Substance Use as a Mediator of the Link between Music Preferences and Adolescent Substance Use

    Science.gov (United States)

    Mulder, Juul; Ter Bogt, Tom F. M.; Raaijmakers, Quinten A. W.; Gabhainn, Saoirse Nic; Monshouwer, Karin; Vollebergh, Wilma A. M.

    2010-01-01

    Both music preferences and the substance use behavior of peers are important elements in explaining adolescent substance use. The extent to which music preference and peer use overlap in explaining adolescent substance use remains to be determined. A nationally representative sample of 7324 Dutch school-going adolescents (aged 12-16) provided data…

  19. Adolescent substance use and unplanned pregnancy: strategies for risk reduction.

    Science.gov (United States)

    Connery, Hilary Smith; Albright, Brittany B; Rodolico, John M

    2014-06-01

    Substance use among adolescents increases the risk of unplanned pregnancies, which then increases the risk of fetal exposure to addictive, teratogenic substances. Specific interventions are necessary to target pregnancy planning and contraception among reproductive-age substance users. Screening for substance use using the CRAFFT is recommended in all health care settings treating adolescent patients. Screening for tobacco and nicotine use is also recommended along with the provision of smoking cessation interventions. Using motivational interviewing style and strategies is recommended to engage adolescents in discussions related to reducing substance use, risky sexual behavior, and probability of unplanned pregnancy or late-detection pregnancy.

  20. Alcohol and Substance Use Disorders in DSM-5

    Directory of Open Access Journals (Sweden)

    Gulcan Gulec

    2015-12-01

    Full Text Available When we compare the categories about alcohol, and substance-related disorders in DSM-IV and DSM-5, the new category, named addictive disorders is the most striking change. Only gambling disorder have been identified currently in this category. This may be the most remarkable change among the changes in the DSM-5. Because the expansion of the existing diagnostic criteria may cause the assessment of and lsquo;normal behavior' as a disorder. Additionally, withdrawal of caffeine and cannabis are defined in the DSM-5. Disorders collected under the title of substance-related disorders in the DSM-IV were collected under the name of substance-related and addictive disorders in the DSM-5. Specific criterias for substance abuse and substance addiction have been combined into the name of "substance use disorders". In substance abuse, "experienced legal problems" criteria was removed and "a strong desire or urge or craving for substance use" criteria has been introduced. Henceforth, substance abuse is defined as a mild form of substance use disorders in the DSM-5. A change in the prevalence of substance use disorders should be investigated by the new researches.

  1. Substance Use among Muslim Students in Aceh, Indonesia

    Directory of Open Access Journals (Sweden)

    Inda Mariana Harahap

    2012-08-01

    Full Text Available Background: Illicit substance use is a serious social problem faced by adolescents worldwide, including adolescents in Aceh and has many negative consequences. In addition, illicit substance use does not fit with the values of Islamic teaching, and is strictly prohibited in Islam. Purpose: The aims of this paper are to determine the prevalence of illicit substance use, the stages of substance use, and types of substance used among Muslim students in senior high schools in Aceh, Indonesia. Method: Four hundred and twenty six students who met the inclusion criteria were recruited from four senior high schools in Banda Aceh by using simple random sampling, and of these, 290 returned a completed questionnaire. A self reported questionnaire was used to collect data. Result: The mean age of the subjects was 15.9 years old and the majority of them were female (68.6%. The study found that the prevalence of substance use was 2.4%with a higher number of females than males who had used illicit substances. The common substances that were used by the students were marijuana and dextromethorphon, as well as intentionally inhaled substances. Lastly, out of the students who had used illegal substances the majority was in the regular use stage (1.4%. Conclusion: This study found that substance use among Muslim students in Aceh exists, although prevalence was low. Thus, several preventive programs may be needed in Aceh not only for Muslims students who have used substances but also for students who have not use illegal substances. Keywords: Adolescents, Substance use, Muslim students, Indonesia.

  2. 76 FR 20994 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2011-04-14

    ... Abuse and Mental Health Services Administration's Center for Substance Abuse Prevention Drug Testing... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... meeting of the Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for...

  3. 78 FR 69702 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2013-11-20

    ... and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Prevention (CSAP) Drug... Abuse and Mental Health Services Administration's Center for Substance Abuse Prevention Drug Testing... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance...

  4. Failure to get into substance abuse treatment.

    Science.gov (United States)

    Fisher, Dennis G; Reynolds, Grace L; D'Anna, Laura H; Hosmer, David W; Hardan-Khalil, Kholoud

    2017-02-01

    Among substance abusers in the US, the discrepancy in the number who access substance abuse treatment and the number who need treatment is sizable. This results in a major public health problem of access to treatment. The purpose of this study was to examine characteristics of Persons Who Use Drugs (PWUDs) that either hinder or facilitate access to treatment. 2646 participants were administered the Risk Behavior Assessment (RBA) and the Barratt Impulsiveness Scale. The RBA included the dependent variable which was responses to the question "During the last year, have you ever tried, but been unable, to get into a drug treatment or detox program?" In multivariate analysis, factors associated with being unable to access treatment included: Previously been in drug treatment (OR=4.51), number of days taken amphetamines in the last 30days (OR=1.18), traded sex for drugs (OR=1.53), homeless (OR=1.73), Nonplanning subscale of the Barratt Impulsiveness Scale (OR=1.19), age at interview (OR=0.91), and sexual orientation, with bisexual men and women significantly more likely than heterosexuals to have tried but been unable to get into treatment. The answers to the question on "why were you unable to get into treatment" included: No room, waiting list; not enough money, did not qualify, got appointment but no follow through, still using drugs, and went to jail before program start. As expected, findings suggest that limiting organizational and financial obstacles to treatment may go a long way in increasing drug abuse treatment accessibility to individuals in need. Additionally, our study points to the importance of developing approaches for increasing personal planning skills/reducing Nonplanning impulsivity among PWUDs when they are in treatment as a key strategy to ensure access to additional substance abuse treatment in the future.

  5. GABA systems, benzodiazepines, and substance dependence.

    Science.gov (United States)

    Malcolm, Robert J

    2003-01-01

    Alterations in the gamma-aminobutyric acid (GABA) receptor complex and GABA neurotransmission influence the reinforcing and intoxicating effects of alcohol and benzodiazepines. Chronic modulation of the GABA(A)-benzodiazepine receptor complex plays a major role in central nervous system dysregulation during alcohol abstinence. Withdrawal symptoms stem in part from a decreased GABAergic inhibitory function and an increase in glutamatergic excitatory function. GABA(A) receptors play a role in both reward and withdrawal phenomena from alcohol and sedative-hypnotics. Although less well understood, GABA(B) receptor complexes appear to play a role in inhibition of motivation and diminish relapse potential to reinforcing drugs. Evidence suggests that long-term alcohol use and concomitant serial withdrawals permanently alter GABAergic function, down-regulate benzodiazepine binding sites, and in preclinical models lead to cell death. Benzodiazepines have substantial drawbacks in the treatment of substance use-related disorders that include interactions with alcohol, rebound effects, alcohol priming, and the risk of supplanting alcohol dependency with addiction to both alcohol and benzodiazepines. Polysubstance-dependent individuals frequently self-medicate with benzodiazepines. Selective GABA agents with novel mechanisms of action have anxiolytic, anticonvulsant, and reward inhibition profiles that have potential in treating substance use and withdrawal and enhancing relapse prevention with less liability than benzodiazepines. The GABA(B) receptor agonist baclofen has promise in relapse prevention in a number of substance dependence disorders. The GABA(A) and GABA(B) pump reuptake inhibitor tiagabine has potential for managing alcohol and sedative-hypnotic withdrawal and also possibly a role in relapse prevention.

  6. Randomization in substance abuse clinical trials

    Directory of Open Access Journals (Sweden)

    Woolson Robert F

    2006-02-01

    Full Text Available Abstract Background A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distributions. Numerous randomization techniques, each with varying properties of randomness and balance, are suggested in the statistical literature. This paper reviews common randomization techniques often used in substance abuse research and an application from a National Institute on Drug Abuse (NIDA-funded clinical trial in substance abuse is used to illustrate several choices an investigator faces when designing a clinical trial. Results Comparisons and contrasts of randomization schemes are provided with respect to deterministic and balancing properties. Specifically, Monte Carlo simulation is used to explore the balancing nature of randomization techniques for moderately sized clinical trials. Results demonstrate large treatment imbalance for complete randomization with less imbalance for the urn or adaptive scheme. The urn and adaptive randomization methods display smaller treatment imbalance as demonstrated by the low variability of treatment allocation imbalance. For all randomization schemes, covariate imbalance between treatment arms was small with little variation between adaptive schemes, stratified schemes and unstratified schemes given that sample sizes were moderate to large. Conclusion We develop this paper with the goal of reminding substance abuse researchers of the broad array of randomization options available for clinical trial designs. There may be too quick a tendency for substance abuse researchers to implement the fashionable urn

  7. [Is nutritional obesity a substance use disorder?

    Science.gov (United States)

    Albayrak, Özgür; de Zwaan, Martina

    2016-12-01

    Today, food addiction has become an increasing area of research. Multiple studies aim to characterize individuals in terms of food addiction based on the assumption, that hyperpalatable foods rich of salt, sugar and fat may induce a cluster of behavioral changes that may resemble a substance use disorder, despite the fact that to date there is no evidence, that nutritional factors lead to an addictive eating-like behavior in humans. In this review article, we aim to introduce the basic experiments, that build the framework upon which food addiction is being investigated and to critically discuss the concept of food addiction.

  8. Protective factors of substance use in youth subcultures.

    Science.gov (United States)

    Bobakova, Daniela; Geckova, Andrea Madarasova; Klein, Daniel; Reijneveld, Sijmen A; van Dijk, Jitse P

    2012-09-01

    Youth subcultures, characterized by a distinctive lifestyle, music preference, shared values and behaviors, are associated with substance use. The aim of this study was to explore whether protective factors such as parental monitoring, parental bonding and parental substance abstinence affect the association between subculture affiliation and adolescents' substance use. We used data from 15-year-old elementary school pupils (N=1380; mean age=15.47; response 79.5%) who participated in the Health Behaviour in School Aged Children 2009/2010 study. The association between subculture affiliation and substance use (smoking, drinking alcohol, drunkenness, and cannabis use) was adjusted for parental monitoring, parental bonding and parental substance abstinence for boys and girls separately using logistic regression. Adolescents affiliated to one of the selected youth subcultures were significantly more likely to use substances than other 15-years-olds, except for cannabis use in girls. Adjustment for parental monitoring reduced the association between subculture affiliation and substance use by 31-64% in girls and by 10-23% in boys. Adjustment for parental bonding and parental substance abstinence led to no changes or minor changes. After adjustments for protective factors, subculture affiliation remained significantly associated with substance use. The role of protective factors in adolescents with a subculture affiliation regarding substance use is rather limited. Our findings imply that preventive strategies targeting youth subcultures should take protective factors into account and be gender-specific.

  9. Periodontal Status amongst Substance Abusers in Indian Population.

    Science.gov (United States)

    Reddy, Shantipriya; Kaul, Sanjay; Agrawal, Chaitali; Prasad, M G S; Agnihotri, Jaya; Bhowmik, Nirjhar; Amudha, D; Kambali, Soumya

    2012-01-01

    Background. In India there have been limited number of studies on periodontal status among drug addicts, and thus this study aims to assess the Oral hygiene and periodontal status in substance abusers and compare it with non-substance abusers. Methods. A comparative study was conducted to assess the periodontal status in substance abusers. Non-substance abusers were procured from the general population of Bangalore. From the control group 250 non-substance abusers were age and sex matched with the study population of substance abusers. The oral hygiene and periodontal condition of all subjects was assessed using Oral hygiene index- simplified (OHI-S), Russell's periodontal indices and Gingival bleeding index. Results. The mean of OHI-S and Periodontal Index (Russell's Index) scores were higher (2.70 and 3.68, resp.) in substance abusers than the control group (2.45 and 2.59, resp.). The mean Gingival bleeding score was lower (9.69) in substance abusers than the control group (22.7) and found to be statistically significant. A positive correlation found between OHI-S and Russell's periodontal index whereas negative correlation was found between OHI-S and Gingival bleeding in substance abusers. Conclusions. Though the oral hygiene was fair, more periodontal destruction and less of gingival bleeding were observed in substance abusers as compared to control group.

  10. Evidence based psychosocial interventions in substance use

    Directory of Open Access Journals (Sweden)

    Sonali Jhanjee

    2014-01-01

    Full Text Available In recent years, there has been significant progress and expansion in the development of evidence-based psychosocial treatments for substance abuse and dependence. A literature review was undertaken using the several electronic databases (PubMed, Cochrane Database of systemic reviews and specific journals, which pertain to psychosocial issues in addictive disorders and guidelines on this topic. Overall psychosocial interventions have been found to be effective. Some interventions, such as cognitive behavior therapy, motivational interviewing and relapse prevention, appear to be effective across many drugs of abuse. Psychological treatment is more effective when prescribed with substitute prescribing than when medication or psychological treatment is used alone, particularly for opiate users. The evidence base for psychological treatment needs to be expanded and should also include research on optimal combinations of psychological therapies and any particular matching effects, if any. Psychological interventions are an essential part of the treatment regimen and efforts should be made to integrate evidence-based interventions in all substance use disorder treatment programs.

  11. The antioxidative substances in cacao liquor.

    Science.gov (United States)

    Osakabe, N; Yamagishi, M; Sanbongi, C; Natsume, M; Takizawa, T; Osawa, T

    1998-04-01

    The antioxidative substances contained in cacao liquor, which is one of the major ingredients of chocolate, were separated by column chromatography and high-performance liquid chromatography. Three major compounds were purified and two of them were identified by 1H, 13C NMR and mass spectra as (-)-epicatechin (EC) and (+)-catechin (CA). Their antioxidative activity was measured by monitoring the peroxide value of linoleic acid and the thiobarbituric acid-reactive substance values of erythrocyte ghost membranes and microsomes. EC and CA had strong antioxidative effects in all three methods, but one unidentified peak was found to be less effective. Additionally, we analyzed the polyphenol concentration of cacao liquor extractions produced in several countries. The total polyphenol concentration was 7.0 to 13.0%, catechin concentration was 0.31 to 0.49%, and epicatechin concentration was 0.35 to 1.68% in the extractions. It is believed that chocolate is stable against oxidative deterioration on account of the presence of these polyphenolic compounds, and it is also expected to have a protective role against lipid peroxidation in living systems.

  12. Mutagenic compounds from chlorination of humic substances

    Science.gov (United States)

    Holmbom, Bjarne

    Chlorination of natural humic substances, as well as of lignin, produces a myriad of non-chlorinated and chlorinated compounds. The identification of an important class of strongly mutagenic compounds is reviewed. The most important Ames mutagen in chlorinated drinking waters of various origin is the compound 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone ("MX"). This compound occurs at neutral pH in the acyclic form, i.e. in the form of Z-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid. Its E-isomer (E-MX) is present in chlorinated drinking waters at a similar concentration, but is less mutagenic in Ames test. Both oxidised and reduced forms of MX and E-MX are also present in chlorinated waters. The present knowledge of the chemistry and toxicology of these mutagens is examined. The formation and possible elimination of the chlorination mutagens is discussed. The need of understanding the mechanisms of formation of these mutagens from humic substances during drinking water chlorination is emphasized.

  13. Substance dependence among those without symptoms of substance abuse in the World Mental Health Survey.

    Science.gov (United States)

    Lago, Luise; Glantz, Meyer D; Kessler, Ronald C; Sampson, Nancy A; Al-Hamzawi, Ali; Florescu, Silvia; Moskalewicz, Jacek; Murphy, Sam; Navarro-Mateu, Fernando; Torres de Galvis, Yolanda; Viana, Maria Carmen; Xavier, Miguel; Degenhardt, Louisa

    2017-02-17

    The World Health Organization (WHO) World Mental Health (WMH) Survey Initiative uses the Composite International Diagnostic Interview (CIDI). The first 13 surveys only assessed substance dependence among respondents with a history of substance abuse; later surveys also assessed substance dependence without symptoms of abuse. We compared results across the two sets of surveys to assess implications of the revised logic and develop an imputation model for missing values of lifetime dependence in the earlier surveys. Lifetime dependence without symptoms of abuse was low in the second set of surveys (0.3% alcohol, 0.2% drugs). Regression-based imputation models were built in random half-samples of the new surveys and validated in the other half. There were minimal differences for imputed and actual reported cases in the validation dataset for age, gender and quantity; more mental disorders and days out of role were found in the imputed cases. Concordance between imputed and observed dependence cases in the full sample was high for alcohol [sensitivity 88.0%, specificity 99.8%, total classification accuracy (TCA) 99.5%, area under the curve (AUC) 0.94] and drug dependence (sensitivity 100.0%, specificity 99.8%, TCA 99.8%, AUC 1.00). This provides cross-national evidence of the small degree to which lifetime dependence occurs without symptoms of abuse. Imputation of substance dependence in the earlier WMH surveys improved estimates of dependence.

  14. Sludge management paradigms: impact of priority substances and priority hazardous substances

    DEFF Research Database (Denmark)

    Eriksson, Eva; Lundy, L.; Donner, E.

    2011-01-01

    differing local conditions contain a range of PS/PHS including substances whose use has been banned or heavily restricted. Concentrations reported in this study do not exceed the limit values set for the four PS/PHS currently included in the EU Sewage Sludge Directive. However, more stringent national...

  15. [Responsibilities of enterprises introducing new dangerous chemical substances and preparations].

    Science.gov (United States)

    Cieśla, Jacek; Majka, Jerzy

    2004-01-01

    The paper reviews the responsibilities of producers, importers and distributors set in a new Act of January 2001 on chemical substances and preparations (Off. J. 2001, No. 11, item 84, with subsequent amendments). This Act together with executive provisions is aimed at harmonizing Polish legislation with EU requirements. The Act sets conditions, restriction and bans of production placing on the market and use of chemical substances and preparations in order to protect human health and environment against their harmful effects. The Act together with a number of executive provisions render those who introduce dangerous chemicals and chemical preparations, including distributors responsible for: classification and labelling of dangerous chemical substances and preparations; possessing, making available and up-dating safety data sheets; supplying packages containing certain dangerous substances with child-proof fastenings; notifying the Inspector for Chemical Substances and Preparations about placing a dangerous preparation on the market; notifying the Inspector about a new substance and conducting required studies; being properly qualified to handle dangerous substances. The Act strictly defines the term "placing a substance or a preparation on the market"--it means making a substance or a preparation available to third parties on the territory of The Republic of Poland, territories of the Member States of the European Union or the territory of Iceland, Liechtenstein and Norway, unless the Act provides otherwise; it also means introduction of a substance or a preparation from outside of the territory referred to above on the customs territory of The Republic of Poland, or that of the member states of the European Union and other states listed above. In addition, some of the responsibilities defined by the provisions of the law on chemical substances and preparations are also applicable to handling of biocidals, which are classified as dangerous substances. The Act

  16. Substance use, need, and demand for substance user treatment services in patients treated for sexually transmitted diseases in michigan.

    Science.gov (United States)

    Aktan, G B; Calkins, R F; Johnson, D R

    2001-10-01

    The association between substance use and communicable diseases, and the need for substance user treatment services for patients treated for communicable diseases, is well documented. This study builds upon this knowledge in that it quantifies the need and demand for substance user treatment services in a large population of patients treated for communicable diseases, specifically, sexually transmitted diseases (STDs), an area in which there is insufficient research published in the literature, but which is essential for policy development. More than 1700 patients treated for STDs in publicly funded clinics in Michigan between 1994-1995 were interviewed about their substance use, consequences of use and demand for substance user treatment services. Results indicated that the rates of substance use and demand for substance user treatment services were significantly higher among persons encountered in the STD clinics compared to the Michigan general adult population; however, a large proportion of STD patients determined to need substance user treatment services according to DSM-III-R criteria for "substance dependence" and "abuse" did not report ever receiving it. These results are followed by a discussion of possible policy implications for planning for substance user treatment services for patients treated for STDs in publicly funded clinics and suggestions for further research.

  17. Per and polyfluorinated substances in the Nordic Countries

    DEFF Research Database (Denmark)

    Posner, Stefan; Roos, Sandra; Brunn Poulsen, Pia;

    prioritized in 2) There is a lack of physical chemical data, analystical reference substances, human and environmental occurrence and toxicology data, as well as market information regarding PFCs other than PFOA and PFOS and the current legislation cannot enforce disclosure of specific PFC substance......This Tema Nord report presents a study based on open information and custom market research to review the most common perfluorinated substances (PFC) with less focus on PFOS and PFOA. The study includes three major parts: 1) Identification of relevant per-and polyfluorinated substances...... and their use in various industrial sectors in the Nordic market by interviews with major players and database information 2) Emissions to and occurence in the Nordic environment of the substances described in 1) 3) A summary of knowledge of the toxic effects on humans and the environment of substances...

  18. Symbolism and rationality in the politics of psychoactive substances.

    Science.gov (United States)

    Room, Robin

    2005-01-01

    Psychoactive substances take on many symbolic meanings, and thus the politics of psychoactive substances has featured symbolic elements, or value-based rationality, alongside and often dominating instrumental rationality. Drawing particularly on the work of Joseph Gusfield and Nordic scholars, the chapter considers the symbolic dimension in the politics of substance use, even in Nordic countries celebrated for their societal commitment to knowledge-based policymaking, and its effects on the interplay of science and policy.

  19. Rethinking Substance Use and Abuse among Hospitality Employees

    Directory of Open Access Journals (Sweden)

    Amir Shani

    2016-05-01

    Full Text Available Prevalent substance use among hospitality employees appears to be the norm, but should this be a cause of concern for employers and the industry as a whole? This commentary illustrates the main shortcomings of current references in the hospitality literature to substance use among employees, calling for a cautious and skeptical approach on the part of hospitality scholars and practitioners in the face of a general alarmism regarding the impact of substance use on the workplace

  20. Adolescent Suicidal Behavior and Substance Use: Developmental Mechanisms

    Directory of Open Access Journals (Sweden)

    Donald M. Dougherty

    2008-01-01

    Full Text Available Adolescent suicidal behaviors and substance use are disturbingly common. Research suggests overlap of some of the etiological mechanisms for both adolescent suicidal behavior and substance use, yet clear understanding of the complex relations between these behaviors and their causal underpinnings is lacking. A growing body of evidence and a diathesis model (Mann et al. 1999; Mann, 2003 highlight the importance of impulse control as a proximal risk factor for adolescent suicidal and substance use behaviors. This literature review extends current theory on the relationships between adolescent suicidal behavior and substance use by: (1 examining how, when, and to what extent adolescent development is affected by poor impulse control, stressful life events, substance use behavior, and biological factors; (2 presenting proposed causal mechanisms by which these risk factors interact to increase risk for suicidal behaviors and substance use; and (3 proposing specific new hypotheses to extend the diathesis model to adolescents at risk for suicide and substance use. More specifically, new hypotheses are presented that predict bidirectional relationships between stressful life events and genetic markers of 5-HT dysregulation; substance use behavior and impulsivity; and substance use behavior and suicide attempts. The importance of distinguishing between different developmental trajectories of suicidal and substance use behaviors, and the effects of specific risk and protective mechanisms are discussed. Use of new statistical approaches that provide for the comparison of latent growth curves and latent class models is recommended to identify differences in developmental trajectories of suicidal behavior and substance use. Knowledge gained from these prospective longitudinal methods should lead to greater understanding on the timing, duration, and extent to which specific risk and protective factors influence the outcomes of suicidal behavior and substance

  1. Creativity and Psychoactive Substance Use: A Systematic Review

    OpenAIRE

    2016-01-01

    The role of psychoactive substance use in the research of artistic creation and creativity is a long-standing topic. Ever since the discovery of LSD, researchers have examined the relationship between the effects of chemical substances and the artistic creative process. The goal of the present study was to systematically review all published empirical publications and case reports in refereed journals that focused on the relationship between psychoactive substances and creativity/creative art...

  2. Collecting substance use data with an anonymous mailed survey.

    Science.gov (United States)

    Trinkoff, A M; Storr, C L

    1997-10-25

    Because mailed surveys minimize personal contact, they are useful for collecting sensitive data on substance use, as long as the problems of achieving adequate response rates can be conquered. To address these issues, we report on an anonymous mailed survey of substance use with a 78% response rate, including data collection and survey methods. Analysis of sociodemographic effects on responding found certain groups required additional contacts. Substance use estimates were not affected by non-response bias, suggesting that anonymous mailed surveys can be a feasible means of collecting data on substance use.

  3. Perceived harmfulness of substance use: A pilot study

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2014-01-01

    Full Text Available Background: Harm ratings of substances help in understanding the perception toward substance use and formulating policies. Evidence of such harm ratings by substance users and their caregivers provides a clearer perspective of those who experience and observe such harm closely. Materials and Methods: Substance users and their caregivers were recruited from the Drug De-addiction and Treatment Centre of PGIMER, Chandigarh. Sociodemographic details of the subjects were noted. The subjects were then asked to rate a list of psychoactive preparations according to the harms they thought the preparation caused. The list of substances was developed taking into consideration substance commonly encountered in the geographical area. The harm ratings were transformed on a scale of 0-100. Results: All subjects were males and majority of them were educated above 10 th standard, were not employed and belonged to urban background. Most of them had taken psychoactive substances in their lifetimes but were currently abstinent. Most of the subjects endorsed intravenous drugs as the most harmful, followed by heroin. Beer and chewable tobacco considered the least harmful substances. Greater degree of education was associated with lower harm rankings for heroin, cannabis, dextropropoxyphene, and raw opium; while urban residence was associated with greater harm ratings for cannabis and raw opium. Differences in the harms were perceived for different preparations of the same active compound for alcohol and nicotine. Conclusion: Harm ratings of substances can be a useful guide while formulating policies and allocating resources. Need for further research extending this pilot study is emphasized.

  4. Methylphenidate and dextroamphetamine abuse in substance-abusing adolescents.

    Science.gov (United States)

    Williams, Robert J; Goodale, Leslie A; Shay-Fiddler, Michele A; Gloster, Susan P; Chang, Samuel Y

    2004-01-01

    The prevalence of methylphenidate and dextroamphetamine misuse and abuse was examined in 450 adolescents referred for substance abuse treatment. Twenty three percent reported nonmedical use of these substances and six percent were diagnosed as methylphenidate or dextroamphetamine abusers. Abuse was more common in individuals who were out of school and had an eating disorder. Methylphenidate and dextroamphetamine abuse appears to be much less common than abuse of most other substances. It does occur, however, and parents and schools need to exert greater control over the dispensing of these medications. Physicians are advised to prescribe non-stimulant medications (eg, bupropion) when treating attention deficit hyperactivity disorder in substance-abusing individuals.

  5. Getting boozy in books: substance use in adolescent literature.

    Science.gov (United States)

    Coyne, Sarah M; Callister, Mark; Phillips, James C

    2011-09-01

    Media effects research provides evidence for a link between adolescent exposure to media portrayals of substance use and usage. Exposure to media content that glamorizes and normalizes substance use carries potential public health risks. Though substance use has been examined in other media, such as film, television, and magazines, no research to date examines usage portrayals in adolescent novels. Given that adolescents do read, and given the potential impact of content on adolescent attitudes and behavior, this study provides a detailed analysis of the frequency and nature of substance use in the understudied area of novels. Substance use was examined in 40 best-selling adolescent novels on the New York Times Best Sellers list (time span June-July 2008). Substance use varied widely. Of the various types of substances, alcohol portrayals were most common. Almost all substance use was portrayed as having no consequences. Alcohol use was portrayed in similar frequencies in books aimed at younger, middle, and older adolescents, though illegal drug use was more likely to be found in books aimed at older ages. Our results suggest that the manner in which substance use is generally portrayed may encourage use among adolescents. Researchers, parents, and adolescents are encouraged to examine books as one potentially overlooked area of influence.

  6. 76 FR 51401 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-08-18

    ... classes of controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I The... customers. In reference to drug code 7360 (Marihuana), the company plans to bulk manufacture cannabidiol...

  7. 76 FR 5829 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-02-02

    ... controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II... distribution to its customers. In reference to drug code 7360 (Marihuana), the company plans to...

  8. 76 FR 17968 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-03-31

    ... controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I Alphamethadol (9605) I... code 7360 (Marihuana), the company plans to bulk manufacture cannabidiol as a synthetic...

  9. Substance use disorder and the family: An Indian perspective

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2016-01-01

    Full Text Available The substance use disorder not only impacts the patient himself/herself, but also affects family members. This is more relevant in a country like India where the familial ties are stronger with family members playing a significant role in the treatment process. This narrative review takes an overview of the inter-relationship between substance use disorder and the family. The domestic violence and adverse familial circumstances, both often arise as a consequence of substance use. Although the spouses of substance users experience greater rates of psychopathology and distress, children of patients with substance user disorders demonstrate higher levels of behavioral disturbances. Codependence often develops in the familial relationship, which perpetuates the substance use disorder. Substance use places quite a burden on the family, both psychologically as well as in terms of resources. Nonetheless, family members provide motivation, emotional support, and practical help during the treatment of substance use disorders and hence need to be engaged in the therapeutic process. Finally, the changing family structure and family dynamics in India might influence the in the future both the effect of substance use disorder on the family, and the familial resource available for treatment.

  10. Epidemiology of Substance Use among University Students in Sudan

    Directory of Open Access Journals (Sweden)

    Tarig Osman

    2016-01-01

    Full Text Available Background. Youth populations are vulnerable to substance use particularly in developing countries where circumstances may be favorable for it. There is no published data on substance use among the youth in Sudan other than on tobacco use. Objectives. The aim of this study was to investigate the prevalence, circumstances, and factors associated with substance use. Methods. An institution-based survey was conducted on a sample of 500 students. Data was collected using a questionnaire designed by the WHO for student drug surveys and analyzed using IBM SPSS version 20. Results. The overall prevalence of substance use is 31%. The current prevalence of tobacco, cannabis, alcohol, amphetamines, tranquilizers, inhalants, opiates, cocaine, and heroin use was 13.7%, 4.9%, 2.7%, 2.4%, 3.2%, 1%, 1.2%, 0.7%, and 0.5%, respectively. Curiosity (33.1% was the main reason for initiation of substance use. The main adverse effects reported were health problems (19.7% and theft (19.7%. Peers (40.9% were the prime source of substance use. On multivariate analysis, male sex was the principle predictor for substance use (AOR: 5.55; 95% CI: 3.38, 9.17. Conclusion. Strategies to control substance use should encompass the role of the university and parents in observing and providing education to improve awareness of substances and their consequences.

  11. Relations between heavy drinking, gender, and substance-free reinforcement.

    Science.gov (United States)

    Skidmore, Jessica R; Murphy, James G

    2010-04-01

    Behavioral economic theory and laboratory research have suggested that substance abuse may be associated with diminished engagement in enjoyable substance-free activities (substance-free reinforcement). However, college students, in particular men, have reported numerous social benefits from drinking that might mitigate the expected inverse relation between drinking and substance-free reinforcement. In this study, we examined the relations between college student heavy drinking, gender, and several categories of substance-free reinforcement (peer, dating, sexual, school, and family activities). Participants were 246 undergraduate students who were classified as a function of their reported frequency of heavy drinking during a typical week in the past month (120 heavy drinkers, 126 light drinkers). Heavy drinking was associated with significantly higher substance-free peer and sexual reinforcement. This association was gender invariant and remained significant in multiple regression models that controlled for gender, ethnicity, and fraternity or sorority membership. Substance-free reinforcement did not predict frequency of heavy drinking in models that included levels of substance-related reinforcement. The results indicate that college student heavy drinking is not associated with global deficits in substance-free reinforcement and is instead associated with increased peer and sexual activity that occurs outside the context of drinking or drug use. Prevention programs should help students to compensate for the potential loss of social reinforcement associated with reductions in drinking.

  12. Can you vaccinate against substance abuse?

    Science.gov (United States)

    Kosten, Thomas R; Domingo, Coreen B

    2013-08-01

    Vaccines are being developed against substance abuse and most progress has been made with anti-cocaine, nicotine and opiate vaccines, but new ones are being developed for methamphetamine and may be in humans within 18 - 24 months. These haptenated vaccines share a common problem in that only about one-third of those vaccinated get a sufficiently robust antibody titer to enable them to effectively block drug use. This problem is being addressed with better carrier proteins and new adjuvants beyond alum. This review provides details about these developing vaccines that act through pharmacokinetic rather than pharmacodynamics blockade. Due to this pharmacokinetic mechanism of keeping abused drugs in the bloodstream and not allowing them entry into the brain or other organs, these vaccines have very few side effects compared to other blockers used in addictions treatment.

  13. The neurobiology of substance and behavioral addictions.

    Science.gov (United States)

    Grant, Jon E; Brewer, Judson A; Potenza, Marc N

    2006-12-01

    Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.

  14. Control substances and alcohol use and testing

    Energy Technology Data Exchange (ETDEWEB)

    Przybylski, J.L.

    1994-07-01

    The Omnibus Transportation Employee Testing Act was signed into law in October of 1991. The Omnibus Transportation Employee Testing Act of 1991 required the United States Department of Transportation (DOT) to enact regulations requiring the testing of employees that perform ``safety sensitive functions`` for illegal controlled substance use and alcohol misuse. The Transportation Management Division, Office of Environmental Restoration and Waste Management (TMD/EM-261), United States Department of Energy (DOE), Training Program Manager is committed to promoting the availability of the necessary information to those affected members of the Department of Energy (DOE) community in an effort to attain the highest possible level of regulatory compliance and to enhance the safety of each individual in the workplace.

  15. Persistent toxic substances: sources, fates and effects.

    Science.gov (United States)

    Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

    2012-01-01

    Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

  16. An holistic approach to substance abuse treatment.

    Science.gov (United States)

    Breslin, Kathy T; Reed, Maria R; Malone, Sandra B

    2003-01-01

    The purpose of this article is to describe a model outpatient substance abuse treatment program. This program is designed to provide patients with not only traditional modalities of treatment such as individual, group, and family therapy, but also to provide an opportunity for patients to express thoughts and feelings through holistic modalities. These modalities include dance/movement therapy, Tai Chi, art therapy, leisure and recreational skills, spiritual growth and development, cultural awareness and appreciation, vocational services, psychiatric care and physical health. The authors describe features of this program that they believe to be unique and that focus on ways to help patients develop a stronger sense of self-identity, self-esteem and self-confidence.

  17. Substance abuse in emergency department patients with unexplained syncope.

    Science.gov (United States)

    Wiener, Zev; Chiu, David Te-Wei; Shapiro, Nathan Ivan; Grossman, Shamai Aron

    2014-04-01

    Current data suggest that up to 60 % of patients presenting to the ED with syncope leave the hospital without a defined etiology. Although a relationship between syncope and substance abuse has been described, no study to date has looked at the relationship between syncope of unknown etiology and substance abuse in patients presenting to the ED. The objective of the study was to determine whether a history of or current substance abuse is associated with an increased incidence of syncope of unknown etiology in ED patients. A prospective, observational, cohort study of consecutive ED patients aged ≥18 who presented with syncope was conducted between 6/03 and 7/06. Patients were queried in the ED and charts reviewed about a history of or current substance abuse. Substance abuse was defined as consumption of >2 alcoholic beverages nightly, repetitive use of any illicit substances, or documentation by the patient's physician of concern regarding suspected substance abuse. Data were analyzed using SAS with Chi-squared and Fisher's exact tests. We enrolled 518 patients who presented to the ED after syncope, 161 of whom did not have an identifiable etiology for their syncopal event. 62 patients had a history of, or current substance abuse. Among patients with a history of, or current substance abuse, 45 % had unexplained syncope, as opposed to 29 % of patients without such a history (p = 0.01). Our results suggest that prior and current substance abuse is associated with increased incidence of syncope of unknown etiology. Patients evaluated in the ED or even hospitalized with syncope of unknown etiology may benefit from substance abuse screening and possibly detoxification referral.

  18. 76 FR 75794 - Significant New Use Rules on Certain Chemical Substances; Withdrawal of Two Chemical Substances

    Science.gov (United States)

    2011-12-05

    ... July 27, 1989 (54 FR 31314). The docket for the direct final SNURs for these two chemical substances... entities is provided in the Federal Register issue of October 5, 2011 (76 FR 61566) (FRL-8880-2). If you..., 1345 (d) and (e), 1361; E.O. 11735, 38 FR 21243, 3 CFR, 1971-1975 Comp. p. 973; 42 U.S.C. 241,...

  19. Young People's Involvement in a Substance Misuse Communications Campaign

    Science.gov (United States)

    Jones, Mathew; Salmon, Debra; Orme, Judy

    2004-01-01

    There is growing emphasis in public policy on involving young people in the development of health promotion campaigns and information resources on substance misuse. To date there has been little literature that explores the level and nature young people's involvement in such initiatives. This paper reports on an evaluation of a substance misuse…

  20. Substance Abuse: Implications for Counseling African American Men.

    Science.gov (United States)

    Wade, Jay C.

    1994-01-01

    Examines factors--such as unemployment, economic deprivation, racism, issues pertaining to gender roles--and their contribution to substance abuse in African American men. Specifically reviews the use of alcohol, opiates, crack, and cocaine. Argues that a biopsychosocial model offers the best framework in conceptualizing substance abuse and…

  1. Protective factors of substance use in youth subcultures

    NARCIS (Netherlands)

    Bobakova, D.; Geckova, A.M.; Klein, D.; Reijneveld, S.A.; van Dijk, J.P.

    2012-01-01

    Youth subcultures, characterized by a distinctive lifestyle, music preference, shared values and behaviors, are associated with substance use. The aim of this study was to explore whether protective factors such as parental monitoring, parental bonding and parental substance abstinence affect the as

  2. Examining the Interface Between Substance Misuse and Intimate Partner Violence

    Directory of Open Access Journals (Sweden)

    Peter M. Monti

    2009-01-01

    Full Text Available There is considerable theoretical and empirical support for a link between substance misuse and perpetration and victimization of intimate partner violence. This review briefly summarizes this literature and highlights current research that addresses the interface between treatment for substance abuse and intimate partner violence. Suggestions for future research and clinical implications are provided.

  3. Prevalence and Pedagogy: Understanding Substance Abuse in Schools

    Science.gov (United States)

    Salm, Twyla; Sevigny, Phil; Mulholland, Val; Greenberg, Hirsch

    2011-01-01

    This case study examines not only the prevalence of substance abuse in one rural, Canadian high school, but also how teachers understand teaching and learning in relation to substance abuse. Over one third of students reported that they had used marijuana (37%) and alcohol (38%) in the last seven days, a rate considerably higher than typical…

  4. New psychoactive substances legislation in Ireland - Perspectives from academia.

    Science.gov (United States)

    Kavanagh, Pierce V; Power, John D

    2014-01-01

    The emergence of 'legal highs' or 'new psychoactive substances' (NPS) on the Irish market is reflective of their appearance in many countries, with some notable exceptions. The official response to the situation is examined here by looking at Irish controlled drugs legislation and drug enforcement policies as enacted in recent years and their effects on academic research on NPS. The philosophy and practice of outright bans of scheduled substances has not been effective in delivering the stated aims of illicit drug control, namely harm reduction. With these legislative changes, we have witnessed the removal of the 'legitimate' sale and open marketing of a number of NPS to the general public in commercial retail premises. However, as legislation was enacted, suppliers and vendors rapidly changed the contents of their legal high products from now controlled to non-controlled substances. We have found that it is administratively challenging to perform scientific research on controlled substances at academic institutions. It is desirable to gather analytical, pharmacological, and toxicological data on these substances as they emerge on the market but due to the restrictive nature of licensing requirements, once a substance or generic class of substances is controlled, this becomes more difficult. The facts that any quantity of substance, no matter how small, is controlled, the nomenclature used to describe compounds is not consistent within the enacted legislation and the use of catch-all classes of compounds with the intention of controlling many similar molecular structures, all create problematic issues for academic researchers.

  5. Transport of radioactive substances; Der Transport radioaktiver Stoffe

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-12-15

    The report on the transport of radioactive substances covers the following topics: facts on radioactive materials transport, safety of the transport of radioactive substances, legal regulations and guidelines: a multiform but consistent system, transport of nuclear fuels, safety during the transport of nuclear fuel, future transport of spent fuel elements and high-level radioactive wastes in Germany.

  6. Divorce, Remarriage, and Adolescent Substance Use: A Prospective Longitudinal Study.

    Science.gov (United States)

    Needle, Richard H.; And Others

    1990-01-01

    Examined substance use in adolescents who experienced parental divorce during childhood, during adolescence, or who were from intact families. Adolescence divorce group had greater overall drug involvement. Divorce had negative effect on boys but not on girls. Custodial parents' remarriage led to increased substance use among girls, decreased…

  7. Psychotropic Medications and Substances of Abuse Interactions in Youth

    Science.gov (United States)

    Kaminer, Yifrah; Goldberg, Pablo; Connor, Daniel F.

    2010-01-01

    The majority of youth with substance use disorders (SUDs) manifest one or more co-occurring psychiatric disorders. Consequently, many of these youths are being prescribed with psychotropic medications. As prescribing rates continue to increase for early-onset psychiatric disorders, potential risk for substance of abuse-psychiatric medication…

  8. Biologically active substances produced by antarctic cryptoendolithic fungi.

    Science.gov (United States)

    Ocampo-Friedmann, R; Friedmann, E I

    1993-01-01

    Researchers report results of laboratory studies of over 200 microbial strains of fungi, algae, cyanobacteria, and heterotrophic bacteria collected in the Ross Desert region of Antarctica. All of the 35 fungal strains produced substances that inhibited the growth of cyanobacteria and algae. The inhibitory effect of the biologically active substance was evident in crushed cell extract but less in spent broth.

  9. 49 CFR 655.52 - Substance abuse professional (SAP).

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Substance abuse professional (SAP). 655.52 Section 655.52 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP...

  10. Ecological Momentary Assessment (EMA) in Studies of Substance Use

    Science.gov (United States)

    Shiffman, Saul

    2009-01-01

    Ecological momentary assessment (EMA) is particularly suitable for studying substance use, because use is episodic and thought to be related to mood and context. This article reviews EMA methods in substance use research, focusing on tobacco and alcohol use and relapse, where EMA has been most applied. Common EMA designs combine event-based…

  11. The Root-inhibiting Substance of Allium Cepa

    NARCIS (Netherlands)

    Stolk, Anth.

    1953-01-01

    Whereas scientific research on inhibiting substances has mainly occupied itself with the effect of these substances on the germination process, I was able to demonstrate the presence of a root-inhibiting agent during my studies on root formation in Fuchsia hybrida and Pelargonium zonale (Stolk, 1952

  12. Adolescent Romantic Couples Influence on Substance Use in Young Adulthood

    Science.gov (United States)

    Gudonis-Miller, Lauren C.; Lewis, Lisa; Tong, Yan; Tu, Wanzhu; Aalsma, Matthew C.

    2012-01-01

    Research has demonstrated that adolescent peer group affiliations are consistent predictors of substance use initiation and maintenance; it is less clear how adolescent "romantic" relationships influence substance use behavior. Data were drawn from the National Longitudinal Study of Adolescent Health. Participants in the final dataset for the…

  13. 75 FR 44287 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-07-28

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated March... Administration (DEA) to be registered as a bulk manufacturer of the basic classes of controlled substances listed....33, the above named company is granted registration as a bulk manufacturer of the basic classes...

  14. 75 FR 69466 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-11-12

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated April... Administration (DEA) to be registered as a bulk manufacturer of the basic classes of controlled substances listed... named company is granted registration as a bulk manufacturer of the basic classes of...

  15. 76 FR 587 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-01-05

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of... registration as a bulk manufacturer of the basic classes of controlled substances listed. Dated: December...

  16. 75 FR 44285 - Manufacturer of Controlled Substances: Notice of Application

    Science.gov (United States)

    2010-07-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances: Notice of Application Pursuant to Sec. 1301... manufacturer of the basic classes of controlled substances listed in schedule II: Drug Schedule...

  17. 77 FR 2324 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2012-01-17

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of... as a bulk manufacturer of the basic classes of controlled substances listed. Dated: January 6,...

  18. 75 FR 6062 - Manufacturer of Controlled Substances Notice of Registration

    Science.gov (United States)

    2010-02-05

    ... Enforcement Administration Manufacturer of Controlled Substances Notice of Registration By Notice dated August... be registered as a bulk manufacturer of the basic classes of controlled substances listed in... named company is granted registration as a bulk manufacturer of the basic classes of...

  19. 76 FR 66994 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301... registered as a bulk manufacturer of the following basic classes of controlled substances: Drug...

  20. 76 FR 44358 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-07-25

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated April... Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of controlled... manufacturer of the basic classes of controlled substances listed. Dated: July 19, 2011. Joseph T....

  1. 75 FR 69467 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-11-12

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated June... Administration (DEA) to be registered as a bulk manufacturer of the basic classes of controlled substances listed... company is granted registration as a bulk manufacturer of the basic classes of controlled...

  2. 75 FR 10314 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-03-05

    ...: 2010-4723] DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances... registered as a bulk manufacturer of the basic classes of controlled substances listed in schedules I and II... company is granted registration as a bulk manufacturer of the basic classes of controlled...

  3. 76 FR 77257 - Manufacturer of Controlled Substances Notice of Registration

    Science.gov (United States)

    2011-12-12

    ... Enforcement Administration Manufacturer of Controlled Substances Notice of Registration By Notice dated August... Administration (DEA) to be registered as a bulk manufacturer of Methamphetamine (1105), a basic class of... registration as a bulk manufacturer of the basic class of controlled substance listed. ] Dated: December...

  4. 75 FR 32506 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-06-08

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the basic classes of controlled... a bulk manufacturer of the basic classes of controlled substances listed. Dated: May 28,...

  5. 75 FR 69464 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-11-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301... Administration (DEA) as a bulk manufacturer of the basic classes of controlled substances listed in schedules...

  6. 76 FR 62451 - Manufacturer of Controlled Substances, Notice of Registration

    Science.gov (United States)

    2011-10-07

    ... Enforcement Administration Manufacturer of Controlled Substances, Notice of Registration By Notice dated June... Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of controlled... registration as a bulk manufacturer of the basic classes of controlled substances listed. Dated: September...

  7. 76 FR 65750 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-10-24

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated June... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of... registration as a bulk manufacturer of the basic classes of controlled substances listed. Dated: October...

  8. 75 FR 62570 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-10-12

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated March... Administration (DEA) to be registered as a bulk manufacturer of methamphetamine (1105), a basic class of... granted registration as a bulk manufacturer of the basic class of controlled substance listed....

  9. 76 FR 36578 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-06-22

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated March... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of... a bulk manufacturer of the basic classes of controlled substances listed. Dated: June 14,...

  10. 76 FR 8777 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-02-15

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated... registered as a bulk manufacturer of the following basic classes of controlled substances: Drug Schedule... with 21 CFR 1301.33, the above named company is granted registration as a bulk manufacturer of...

  11. 75 FR 10313 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-03-05

    ... [Federal Register Volume 75, Number 43 (Friday, March 5, 2010)] [Notices] [Page 10313] [FR Doc No: 2010-4717] DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances... as a bulk manufacturer of the basic classes of controlled substances listed in schedules I and...

  12. 76 FR 51403 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-08-18

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated April... the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following... registration as a bulk manufacturer of the basic classes of controlled substances listed. Dated: August...

  13. The Marihuana Perception Inventory: The Effects of Substance Abuse Instruction.

    Science.gov (United States)

    Gabany, Steve G.; Plummer, Portia

    1990-01-01

    Studied 617 high school and college students prior to and after substance abuse instruction to determine relationship between perceptions and demographic characteristics, and to learn whether substance abuse instruction was related to changes in student's perception of relationships. Findings from Marihuana Perception Inventory showed five factors…

  14. Representing Energy. I. Representing a Substance Ontology for Energy

    Science.gov (United States)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.; Vokos, Stamatis

    2012-01-01

    The nature of energy is not typically an explicit topic of physics instruction. Nonetheless, verbal and graphical representations of energy articulate models in which energy is conceptualized as a quasimaterial substance, a stimulus, or a vertical location. We argue that a substance ontology for energy is particularly productive in developing…

  15. 78 FR 37991 - Alcohol and Controlled Substances Testing

    Science.gov (United States)

    2013-06-25

    ... approaches that maximize net benefits (including potential economic, environmental, public health and safety... Federal Transit Administration 49 CFR Part 655 RIN 2132-AB09 Alcohol and Controlled Substances Testing... to revise sections of the Alcohol and Controlled Substances (D&A) Testing regulation to...

  16. The Spread of Substance Use and Delinquency between Adolescent Twins

    Science.gov (United States)

    Laursen, Brett; Hartl, Amy C.; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Boivin, Michel

    2017-01-01

    This investigation examines the spread of problem behaviors (substance use and delinquency) between twin siblings. A sample of 628 twins (151 male twin pairs and 163 female twin pairs) drawn from the Quebec Newborn Twin Study completed inventories describing delinquency and substance use at ages 13, 14, and 15. A 3-wave longitudinal actor-partner…

  17. Substance Use and the Treatment of Resistant Depression in Adolescents

    Science.gov (United States)

    Goldstein, Benjamin I.; Shamseddeen, Wael; Spirito, Anthony; Emslie, Graham; Clarke, Greg; Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Vitiello, Benedetto; Ryan, Neal; Birmaher, Boris; Mayes, Taryn; Onorato, Matthew; Zelazny, Jamie; Brent, David A.

    2009-01-01

    Objective: Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method: Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of…

  18. Adolescent Romantic Couples Influence on Substance Use in Young Adulthood

    Science.gov (United States)

    Gudonis-Miller, Lauren C.; Lewis, Lisa; Tong, Yan; Tu, Wanzhu; Aalsma, Matthew C.

    2012-01-01

    Research has demonstrated that adolescent peer group affiliations are consistent predictors of substance use initiation and maintenance; it is less clear how adolescent "romantic" relationships influence substance use behavior. Data were drawn from the National Longitudinal Study of Adolescent Health. Participants in the final dataset…

  19. An Analysis of Substance Use among Adolescents from Smaller Places.

    Science.gov (United States)

    Donnermeyer, Joseph F.; Scheer, Scott D.

    2001-01-01

    Examines substance use trends among rural 12th-grade students, 1976-97, based on the national triennial study "Monitoring the Future." Finds that youth from more rural locations generally displayed lower rates of substance use, but as urbanization spread, differences declined. Compares data on farm, rural nonfarm, and small-town youth in both…

  20. Early Adolescent Substance Use/Abuse in Rural Northern Michigan.

    Science.gov (United States)

    Sarvela, Paul D.; McClendon, E. J.

    Basic research and programs in substance abuse dealing directly with rural and small town populations lag far behind those aimed at urban groups, in both quality and quantity. A study was conducted to identify factors related to substance use by a preadolescent and early adolescent rural and small town population. Data were collected from 496…

  1. The Evolution of an Online Substance Abuse Counseling Certificate Program

    Science.gov (United States)

    Crozier, Mary K.

    2012-01-01

    In the field of rehabilitation services, substance abuse counseling requires unique skills. Post-baccalaureate academic certificate programs offer professionals an opportunity to retool or expand their skills and meet licensure needs in this evolving field. East Carolina University's online Substance Abuse Counseling Certificate Program was…

  2. Gender Differences Regarding Peer Influence and Attitude toward Substance Abuse.

    Science.gov (United States)

    Rienzi, Beth M.; And Others

    1996-01-01

    To investigate gender differences in acceptance of substance abuse behavior among adolescents, 968 students were administered a questionnaire to assess their perceptions. Results show that both genders felt that boys would be more approving of teenage substance abuse. Most students were disapproving of a teenager driving after drinking. Other…

  3. Substance Abuse in Rural African-American Populations.

    Science.gov (United States)

    Dawkins, Marvin P.; Williams, Mary M.

    More research into illicit substance abuse in rural African-American communities is needed. The existing literature indicates that patterns of use for licit substances (alcohol and cigarettes) are either similar for rural Blacks and Whites or lower for Blacks. However, the negative health and social consequences of smoking and abusive drinking are…

  4. 76 FR 42731 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-07-19

    ... notice published in the Federal Register on September 23, 1975, (40 FR 43745-46), all applicants for... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... importer of the following basic classes of controlled substances: Drug Schedule Methaqualone (2565)...

  5. 75 FR 160 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-01-04

    ... Federal Register on September 23, 1975, (40 FR 43745-46), all applicants for registration to import a... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... be registered as an importer of the basic classes of controlled substances listed in schedule...

  6. 75 FR 76755 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-12-09

    ... published in the Federal Register on September 23, 1975, (40 FR 43745-46), all applicants for registration... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... Administration (DEA) to be registered as an importer of the basic classes of controlled substances listed...

  7. 75 FR 36684 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-06-28

    ... notice published in the Federal Register on September 23, 1975, (40 FR 43745-46), all applicants for... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... (DEA) to be registered as an importer of the basic classes of controlled substances listed in...

  8. 76 FR 30969 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-05-27

    ... Register on September 23, 1975, (40 FR 43745), all applicants for registration to import a basic class of... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... importer of Remifentanil (9739), a basic class of controlled substance listed in schedule II. The...

  9. 77 FR 16262 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2012-03-20

    ... notice published in the Federal Register on September 23, 1975, 40 FR 43745-46, all applicants for... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958...) to be registered as an importer of Fentanyl (9801), a basic class of controlled substance listed...

  10. 75 FR 65660 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-10-26

    ... the Federal Register on September 23, 1975, (40 FR 43745-46), all applicants for registration to... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958... as an importer of the basic classes of controlled substances listed in schedule II: Drug...

  11. 76 FR 57080 - Importer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-09-15

    ... Enforcement Administration Importer of Controlled Substances; Notice of Registration By Notice dated June 7, 2011, and published in the Federal Register on June 16, 2011, 76 FR 35239, Noramco Inc., 1440 Olympic... be registered as an importer of Phenylacetone (8501), a basic class of controlled substance listed...

  12. 77 FR 21998 - Importer of Controlled Substances: Notice of Application

    Science.gov (United States)

    2012-04-12

    ... notice published in the Federal Register on September 23, 1975, 40 FR 43745-46, all applicants for... Enforcement Administration Importer of Controlled Substances: Notice of Application Pursuant to 21 U.S.C. 958...) to be registered as an importer of Nabilone (7379), a basic class of controlled substance listed...

  13. 75 FR 44285 - Importer of Controlled Substances: Notice of Registration

    Science.gov (United States)

    2010-07-28

    ... Enforcement Administration Importer of Controlled Substances: Notice of Registration By Notice dated April 26, 2010 and published in the Federal Register on April 30, 2010, (75 FR 22844), Penick Corporation, 33... Administration (DEA) to be registered as an importer of the basic classes of controlled substances listed...

  14. 76 FR 77253 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-12-12

    ... noted in a previous notice published in the Federal Register on September 23, 1975, 40 FR 43745, all... Enforcement Administration Importer of Controlled Substances; Notice of Application Pursuant to 21 U.S.C. 958...) to be registered as an importer of Remifentanil (9739), a basic class of controlled substance...

  15. Food contact materials, flavouring substances and smoke flavourings

    Directory of Open Access Journals (Sweden)

    Engel K-H

    2012-10-01

    Full Text Available

    The EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC Panel and the subsequent Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel have undertaken evaluations of the safety of flavourings (both chemically defined substances and mixtures such as smoke flavourings and food contact materials (FCM, as well as assessments on other substances used in food. The major progress in methodologies for the evaluation of the safety of these substances is highlighted in this article. By December 2011, scientific opinions had been adopted for 247 substances for food contact materials, mainly plastics. Adoption of a series of opinions on active and/or intelligent packaging substances and on recycling processes of plastics is planned between July 2012 and December 2013. Panel opinions, EFSA statements/reports and guidance documents were published on specific issues and on substances for which there was an urgent request for safety evaluation (for example isopropylthioxanthone (ITX, bisphenol A (BPA, phthalates, epoxidised soybean oil (ESBO, benzophenone and 4-methylbenzophenone. By 2009, the AFC and CEF Panels had completed the safety review of 2 067 flavourings substances used in the EU. Additional data, which were requested for 404 substances, are currently under evaluation or have been generated. Eleven smoke flavourings have been evaluated, and the CEF Panel has prepared a guidance document on the future data required for the evaluation of flavourings.

  16. Prevalence of substance-related disorders in heart transplantation candidates.

    Science.gov (United States)

    Sirri, L; Potena, L; Masetti, M; Tossani, E; Grigioni, F; Magelli, C; Branzi, A; Grandi, S

    2007-01-01

    Substance abuse cessation is one of the leading factors in determining the eligibility for the heart transplantation waiting list, as noncompliance with this issue may seriously endanger posttransplantation outcomes. Yet, the prevalence of substance-related disorders among candidates for heart transplantation has not been evaluated enough. Eighty three heart transplantation candidates were assessed for prior or current substance-related disorders through the Structured Clinical Interview for mental disorders according to DSM-IV. A prior history of at least one substance-related disorder was found in 64% of patients, with nicotine dependence as the most prevalent diagnosis (61.4% of the sample). Ten subjects were currently smokers, despite heart failure. A prior history of alcohol abuse and caffeine intoxication was found in 9.6% and 2.4% of patients, respectively. Substance abuse or dependence behaviors should be monitored during all the phases of heart transplantation program. Early identification of current substance-related disorders may allow better allocation of organ resources and proper lifestyle modification programs provision. A prior history of substance-related disorders should alert physicians to assess patients for possible relapse, especially after transplantation. The inclusion of a specialist in the assessment and treatment of substance-related disorders in the heart transplantation unit may reduce the risk of unsuccessful outcomes due to noncompliance with an adequate lifestyle.

  17. From substance use to homelessness or vice versa?

    Science.gov (United States)

    McVicar, Duncan; Moschion, Julie; van Ours, Jan C

    2015-07-01

    Homelessness is associated with substance use, but whether substance use precedes or follows homelessness is unclear. We investigate the nature of the relationship between homelessness and substance use using data from the unique Australian panel dataset Journeys Home collected in 4 surveys over the period from October 2011 to May 2013. Our data refer to 1325 individuals who were homeless or at risk of becoming homeless. We investigate dynamics in homelessness and substance use over the survey period. We find that the two are closely related: homeless individuals are more likely to be substance users and substance users are more likely to be homeless. These relationships, however, are predominantly driven by observed and unobserved individual characteristics which cause individuals to be both more likely to be homeless and to be substance users. Once we take these personal characteristics into account it seems that homelessness does not affect substance use, although we cannot rule out that alcohol use increases the probability that an individual becomes homeless. These overall relationships also hide some interesting heterogeneity by 'type' of homelessness.

  18. Subculture affiliation is associated with substance use of adolescents.

    Science.gov (United States)

    Bobakova, Daniela; Madarasova Geckova, Andrea; Reijneveld, Sijmen A; van Dijk, Jitse P

    2012-01-01

    Youth subcultures (hip-hop, punk, skinhead, techno scene, metal) are known for specific lifestyles, music preferences, shared values and behaviours of their members. The aim of this study was to assess the association between subculture affiliation and substance use (tobacco, alcohol and cannabis), and whether gender, family affluence and substance use by peers explain this association. Subculture affiliation was significantly associated with substance use (OR/95% CI: smoking 3.13/2.30-4.24; drinking 2.58/1.95-3.41; drunkenness 2.02/1.54-2.66; cannabis use 2.42/1.46-4.00). Only a part of this risk runs via gender, family affluence and peer substance use. Health promotion should be targeted in particular at adolescents with a subculture affiliation as they are at higher risk of substance use.

  19. Mechanisms of humic substances degradation by fungi

    Science.gov (United States)

    Chen, Y.; Hadar, Y.; Grinhut, T.

    2012-04-01

    Humic substances (HS) are formed by secondary synthesis reactions (humification) during the decay process and transformation of biomolecules originating from plants and other dead organisms. In nature, HS are extremely resistant to biological degradation. Thus, these substances are major components in the C cycle and in the biosphere and therefore, the understanding of the process leading to their formation and transformation and degradation is vital. Fungi active in the decomposition process of HS include mainly ascomycetes and basidiomycetes that are common in the upper layer of forest and grassland soils. Many basidiomycetes belong to the white-rot fungi (WRF) and litter-decomposing fungi (LDF). These fungi are considered to be the most efficient lignin degraders due to their nonspecific oxidizing enzymes: manganese peroxidase (MnP), lignin peroxidase (LiP) and laccase. Although bacteria dominate compost and participate in the turnover of HS, their ability to degrade stable macromolecules such as lignin and HS is limited. The overall objectives of this research were to corroborate biodegradation processes of HS by WRF. The specific objectives were: (i) To isolate, identify and characterize HS degrading WRF from biosolids (BS) compost; (ii) To study the biodegradation process of three types of HS, which differ in their structure, by WRF isolated from BS compost; and (iii) To investigate the mechanisms of HA degradation by WRF using two main approaches: (a) Study the physical and chemical analyses of the organic compounds obtained from direct fungal degradation of HA as well as elucidation of the relevant enzymatic reactions; and (b) Study the enzymatic and biochemical mechanisms involved during HA degradation. In order to study the capability of fungi to degrade HS, seventy fungal strains were isolated from biosolids (BS) compost. Two of the most active fungal species were identified based on rDNA sequences and designated Trametes sp. M23 and Phanerochaetesp., Y6

  20. Substance Flow Analysis of Mercury in China

    Science.gov (United States)

    Hui, L. M.; Wang, S.; Zhang, L.; Wang, F. Y.; Wu, Q. R.

    2015-12-01

    In previous studies, the emission of anthropogenic atmospheric Hg in China as well as single sector have been examined a lot. However, there might have been more Hg released as solid wastes rather than air. Hg stored in solid wastes may be released to air again when the solid wastes experience high temperature process or cause local pollution if the solid wastes are stacked casually for a long time. To trace the fate of Hg in China, this study developed the substance flow of Hg in 2010 covering all the sectors summarized in table 1. Below showed in Figure 1, the total Hg input is 2825t. The unintentional input of Hg, mined Hg, and recycled Hg account for 57%, 32% and 11% respectively. Figure 2 provides the detail information of substance flow of Hg. Byproducts from one sector may be used as raw materials of another, causing cross Hg flow between sectors. The Hg input of cement production is 303 t, of which 34% comes from coal and limestone, 33% comes from non-ferrous smelting, 23% comes from coal combustion, 7% comes from iron and steel production and 3% comes from mercury mining. Hg flowing to recycledHg production is 639 t, mainly from Hg contained in waste active carbon and mercuric chloride catalyst from VCM production and acid sludge from non-ferrous smelting. There are 20 t mercury flowing from spent mercury adding products to incineration. Figure1 and Figure 2 also show that 46% of the output Hg belongs to "Lagged release", which means this part of mercury might be released later. The "Lagged release" Hg includes 809 t Hg contained in stacked byproducts form coal combustion, non-ferrous smelting, iron and steel production, Al production, cement production and mercury mining, 161t Hg stored in the pipeline of VCM producing, 10 t Hg in fluorescent lamps that are in use and 314 t mercury stored in materials waiting to be handled with in recycled mercury plants. There is 112 t Hg stored in landfill and 129 t Hg exported abroad with the export of mercury adding

  1. The Notion of Substance in Physical Theory

    Science.gov (United States)

    Vanzandt, Joseph David

    The thesis explores the philosophical consequences of adopting the view that the principle of non-contradiction, the principle of sufficient reason, and the monistic notion of substance are more closely linked than most modern and contemporary philosophers have supposed. This thesis is then applied to show the connections between the metaphysical views of Spinoza and the view of nature of Albert Einstein. The first chapter is an historical overview of the principles of sufficient reason and non-contradiction, and the notion of substance, followed by a presentation of the reasons that led the author to conclude that the usual treatment of these concepts requires revision. These reasons are based upon substantial cause theory, developed in the 1970s by Richard Cole. The second and third chapters are an interpretation of Book 1 of Spinoza's Ethics from the viewpoint presented in the first chapter. The implicit role of the principles of non-contradiction and sufficient reason in Spinoza's argument is drawn out through an examination of his definitions, axioms and propositions. The third and fourth chapters are an interpretation and criticism of Immanuel Kant. It is first shown that the common dismissal of Kant's philosophy based upon the discovery of non-Euclidean geometries and the denial of strict causality among some physical events is not well founded; ways in which Kant's framework can accommodate these problems are proposed. It is then argued that Kant's criticism of traditional metaphysics is not conclusive. In particular, Kant's arguments against the possibility of an ontological argument are examined and criticisms of his arguments are presented. The sixth and seventh chapters contain an historical account of the development of physics in the 20th century to illustrate the strong tendency toward unification found in science. It is suggested that this natural tendency to seek ever higher levels of unification is evidence that the principle of sufficient reason

  2. Psychoactive substance use by truck drivers: a systematic review.

    Science.gov (United States)

    Girotto, Edmarlon; Mesas, Arthur Eumann; de Andrade, Selma Maffei; Birolim, Marcela Maria

    2014-01-01

    The aim of this study was to summarise the scientific evidence on the prevalence of psychoactive substance use and on the factors associated with their intake among truck drivers. A systematic review was performed in the databases PubMed, Scientific Electronic Library Online, Latin American and Caribbean Health Sciences, and Cochrane and 36 cross-sectional studies were identified with quantitative results about the use of psychoactive substances by truck drivers. Out of these, 28 were carried out in countries with large land areas and 23 obtained their information through self-reporting. The most frequently studied substances were alcohol (n=25), amphetamines (n=17), marijuana (n=16) and cocaine (n=13). The prevalence of the use of these substances greatly varied: alcohol (0.1-91.0%); amphetamines (0.2-82.5%), marijuana (0.2-29.9%), cocaine (0.1-8.3%). The frequency of substance use was lower in studies that investigated the presence of these substances in biological samples than in those based on self-reported use. In 12 studies that evaluated factors associated with the intake of psychoactive substances, the following stood out: younger age, higher income, longer trips, alcohol consumption, driving in the night shift, travelling interstate routes, long or short sleep, fewer hours of rest, little experience of the driver, connection with small and medium sized companies, income below levels determined by labour agreements, productivity-based earnings and prior involvement in accidents. The frequency of psychoactive substance use by truck drivers seems to be high, although that greatly varies according to the type of substance and the method of collecting the information. The use of these substances was mainly associated with indicators of poor working conditions.

  3. Use of psychoactive substances in students at a public university

    Directory of Open Access Journals (Sweden)

    Meire Luci da Silva

    2014-11-01

    Full Text Available Introduction: The use of psychoactive substances by the student population has been the object of various studies in Brazil. Objective: To determine the prevalence of substance use among students. Methods: Quantitative study with a closed questionnaire based on standardized assessment instruments was developed. It consists of questions related to types of psychoactive substance use, abuse, frequency and duration of use, self-criticism regarding the use, consequences of use in relation to health, and misdemeanors committed under the influence of psychoactive substances. The sample included the participation of 268 students. A total of 183 (68.3% questionnaires were analyzed, and only those with positive result for substance abuse at some point in life, the remainder, 85 (31% questionnaires, had negative responses to psychoactive substances. Results: Students’ responses to the two years surveyed indicated that the first psychoactive substance used was alcohol (77.9%, followed by tobacco use (10.9%, and marijuana (7.6%. Of the students surveyed, 145 (79.2% answered that still make use of psychoactive substances, and the current frequency of use varies from one or more times per week. When asked about the possibility of being or becoming drug addicts, 169 (92.3% responded that they are not or will not become dependent. Conclusion: The results indicate the high rate of substance use among college students surveyed, and point to their contradiction to consider such psychoactive substances harmful to their health.

  4. 78 FR 45545 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2013-07-29

    ... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Prevention... meeting will also be available on the SAMHSA Web site after the meeting. Committee Name: Substance...

  5. 77 FR 43344 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2012-07-24

    ... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Prevention..., http://nac.samhsa.gov/ , or by contacting Matthew J. Aumen. Committee Name: Substance Abuse and...

  6. 78 FR 37560 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2013-06-21

    ... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Prevention..., http://nac.samhsa.gov/ , or by contacting Matthew J. Aumen. Committee Name: Substance Abuse and...

  7. Substance-Abusing Parents in the Criminal Justice System: Does Substance Abuse Treatment Improve Their Children's Outcomes?

    Science.gov (United States)

    Phillips, Susan D.; Gleeson, James P.; Waites-Garrett, Melissa

    2009-01-01

    The expansion of the criminal justice system over the last several decades helped to focus attention on children of incarcerated parents, many of whom have parents with substance abuse problems. Since the 1990's, a national grassroots campaign has been underway to make substance abuse treatment an alternative to incarceration for parents who…

  8. Effects of Forgiveness Therapy on Anger, Mood, and Vulnerability to Substance Use among Inpatient Substance-Dependent Clients

    Science.gov (United States)

    Lin, Wei-Fen; Mack, David; Enright, Robert D.; Krahn, Dean; Baskin, Thomas W.

    2004-01-01

    Anger and related emotions have been identified as triggers in substance use. Forgiveness therapy (FT) targets anger, anxiety, and depression as foci of treatment. Fourteen patients with substance dependence from a local residential treatment facility were randomly assigned to and completed either 12 approximately twice-weekly sessions of…

  9. Substance Use among Youth Entering Texas Youth Commission Reception Facilities in 1989. Second Report: Substance Use and Crime.

    Science.gov (United States)

    Wallisch, Lynn S.

    This report presents descriptive information gathered from interviews with 945 youth aged 10-17 entering Texas Youth Commission (TYC) facilities in 1989 and focuses on both the criminal careers of the youth and the relationship between delinquency and substance use. Eighty-one percent of TYC youth reported illicit substance use with a median age…

  10. Antisocial Behavior and Psychoactive Substance Involvement among Hispanic and Non-Hispanic Caucasian Adolescents in Substance Abuse Treatment.

    Science.gov (United States)

    Stewart, David G.; Brown, Sandra A.; Myers, Mark G.

    1997-01-01

    Compared conduct disorder behaviors and substance involvement of Hispanic (n=34) and non-Hispanic Caucasian (n=34) adolescents so as to determine pre-treatment problem behavior. Results indicate that non-Hispanic Caucasian youth were three times as likely to be diagnosed with conduct disorder prior to substance involvement than were their Hispanic…

  11. DBP formation of aquatic humic substances

    Science.gov (United States)

    Pomes, M.L.; Green, W.R.; Thurman, E.M.; Orem, W.H.; Lerch, H.E.

    1999-01-01

    Aquatic humic substances (AHSs) in water generate potentially harmful disinfection by-products (DBPs) such as haloacetic acids (HAAs) and trihalomethanes (THMs) during chlorination. AHSs from two Arkansas reservoirs were characterized to define source, identify meta-dihydroxybenzene (m-DHB) structures as probable DBP precursors, and evaluate predicted HAA and THM formation potentials. Elemental nitrogen content 0.5 ??eq/mg, ??13C values of -27???, and low yields of syringyl phenols found by cupric oxide (CuO) oxidation suggest a pine tree source for the AHSs found in the Maumelle and Winona reservoirs in Little Rock, Ark. CuO oxidation yielded fewer m-DHB structures in Maumelle AHSs than in Winona AHSs. A higher 3,5-dihydroxybenzoic acid (3,5-DHBA) content correlated with increased HAA and THM formation potential. The 3,5-DHBA concentration in Winona AHSs was similar to the range found in AHSs extracted from deciduous leaf litter, twigs, and grass leachates.

  12. IMMOBILISATION OF HUMIC SUBSTANCES USING PLASMA MODIFICATION

    Directory of Open Access Journals (Sweden)

    Pavlína Hájková

    2015-04-01

    Full Text Available This paper presents a study of the immobilization of humic substances (HSs on a polypropylene (PP nonwoven fabric. In order to attach the HSs, the PP nonwoven fabric was modified in a volume of nonthermal atmospheric pressure dielectric barrier discharge (DBD under defined conditions. An unmodified PP nonwoven fabric was used as a reference sample. The modified and unmodified samples were both dipped in an aqueous solution of potassium humate, and then the samples were washed in water and the amount of HSs attached to the PP fabric was monitored. An aqueous solution of cadmium salts was filtered through the treated fabric, the content of Cd2+ in the solution was monitored using ICP-OES analysis, and the Cd2+ sorbed on the fabric was proved by SEM/EDS analysis. The efficiency of the PP plasma modification was proved by XPS analysis, and the presence and the distribution of the HSs along the fibers was proved by SEM analysis.

  13. Adolescent substance use disorders and comorbidity.

    Science.gov (United States)

    Simkin, Deborah R

    2002-04-01

    It is imperative to know what risk factors are more likely to appear during specific developmental stages so that identification and interventions can be used to decrease the risk for future SUD. Continued surveying of risk factors that can occur at any stage in childhood are important to ensure that other risk factors are anticipated and intervened upon as well. Multiple risk factors increase the magnitude of the risk for SUD, and therefore all risk factors should be detected to convert these to protective factors. Screening instruments that can assess risk factors found to increase the risk for substance abuse can be found in examples, such as the Drug Usage Screening Instrument [81] and the Problem-Oriented Screening Instrument for Teenagers. The detection of risk factors by primary care providers is becoming increasingly important. However, other professionals are beginning to recognize that early recognition and treatment can enable a youth to go on to a productive life in other arenas as well. Drug courts and diversion programs are beginning to treat first-time offenders and their families rather than taking the punitive approach. These have proven to be very successful. Primary care physicians also should become familiar with motivational enhancement therapy when confronting a youth with a suspected substance abuse problem [57]. This method has proven to be more effective in getting youth into treatment than the direct, confrontational style, which often puts the youth in a defensive mode. Motivational enhancement therapy includes interventions that are delivered in a neutral and empathetic way. The six components of motivational enhancement therapy (also called FRAMES) include: Feedback on personal impairment Emphasis on personal responsibility Clear advice to change Menu of alternative options Empathy as a counseling style Self-efficacy In this way, a clinician can elicit pros and cons, give advice, provide choices, practice empathy, clarify goals, and

  14. Photocatalytic oxidation of VX-simulation substance.

    Science.gov (United States)

    Kozlova, E; Vorontsov, A; Rima, G; Lion, C; Preis, S

    2007-01-01

    Experimental studies of photocatalytic oxidation (PCO) of VX-gas simulation substance cysteamine-S-phosphate sodium salt (NaHPO3S-CH2-CH2-NH2, CPSS) at various initial concentrations and pH were undertaken. PCO ultimately resulted in complete mineralisation of CPSS. The PCO byproducts of CPSS include acetate, oxalate and trace amounts of formate ions. The formation rates of acetate and phosphate were equal to the rate of degradation of CPSS, which indicates easy breakage of P-S, C-S and C-N bonds. Sulphate was formed more slowly due to stepwise oxidation of reduced sulphur. Amino group, generally transformed to ammonia, was partially oxidised to nitrite and nitrate in alkaline media. The fastest mineralisation in terms of both TOC degradation and phosphate formation was observed in neutral media. Under neutral media conditions, the PCO rate increased linearly with the CPSS concentration increase. The maximum efficiency by TOC degradation was observed as large as 77 mg per Wh of incident UV flux with quantum efficiency 3.8%.

  15. Immigration and use of psychoactive substances

    Directory of Open Access Journals (Sweden)

    Missouridou E.

    2016-01-01

    Full Text Available Introduction: In the context of deep economic and socio-cultural crisis and the massive influx of immigrants in our country, health professionals are called to meet the needs of immigrants who use psychoactive substances. Purpose: This study aims at investigating the problematic use of alcohol and drugs by immigrants and addressing effectively their needs. Method: Study of Greek and international literature from online databases and journals. Conclusions: Acculturation stress, high degree of acculturation and acculturation gap between different generations of immigrants are associated with high rates of addiction. In the case of new immigrants, who are experiencing the acculturation gap to the previous generation as well as the difficulty to establish an identity that synthesizes elements from both cultures , the subculture of use is often a way of seeking support which they are unable to find in their family or other cultural groups. The efforts to provide culturally competent care require self-knowledge and awareness related to beliefs, attitudes, and stereotypes about the culturally different at a both personal and collective level (organizations, cultural groups, society.

  16. Naturally occurring toxic substances in foods.

    Science.gov (United States)

    Gross, R L; Newberne, P M

    1977-11-01

    Numerous chemical toxins, including normal components of natural foods, e.g., mycotoxins, and toxic chemicals as contaminants such as pesticides, fertilizers, food additives, and preservatives, which are potentially toxic to humans, are discussed. Potential toxicity, the hazard to man represented by most of these chemicals, may be low because the concentration in food may be low. The gap in our knowledge of long-term effects makes rational decisions as to allowable levels of these substances a major problem. On the other hand, nitrosamines and aflatoxins are toxins for which there exists a voluminous literature documentaing extreme biologic activity in experimental animals and indirect evidence for activity in man. Epidemiologic evidence has linked them to human cancers, and because of increasing evidence of long-term human exposure to these toxins either as inadvertent contaminants during food preparation or as the metabolites of mycotic infestation this possible hazard demands intensive investigation. An exhaustive review of data from epidemiologic surveys in various parts of the world, as well as from long-term laboratory studies, represents an impressive start in this direction.

  17. Pyrethroid as a Substance of Abuse

    Directory of Open Access Journals (Sweden)

    Pravesh Sharma

    2014-01-01

    Full Text Available This is a case of a 22-year-old Hispanic male with a history of bipolar disorder and methamphetamine dependence who was admitted after presenting with suicidal ideations by slashing his throat with a machete. The patient had been smoking and inhaling “processed” pyrethroid for about eight weeks as an inexpensive methamphetamine substitute. He reported experiencing a “rush” similar to methamphetamine after using pyrethroid from liquid insecticide that had been heated (electrocuted or sprayed on hot metal sheets until it crystallized. The patient presented with no significant physical markings or findings but claimed to have his suicidal ideations precipitated by concerns of ill effects of pyrethroid on his health. He also had positive urine drug screen for methamphetamine, which he admitted to using on the day of admission. We conclude that it is important for physicians to maintain a high level of suspicion for alternate and uncommon substances of abuse as well as risks for suicidal tendencies in these patients.

  18. Study on Water—Soluble Organic Reducing Substances.I.Determination of Organic Reducing Substances by Differential Pulse Voltammetry

    Institute of Scientific and Technical Information of China (English)

    WUYOU-XIAN; DINGCHANG-PU

    1991-01-01

    A new method was proposed for study of organic reducing substances in soils.According to the theoretical relationship between the voltammetric behaviors and reduction-oxidation reaction of reducing substances,the working conditions of differential pulse voltammetry (d.p.v.)for determining the organic reducing substances produced during the processes of the anaerobic decomposition of plant materials were established with a glass carbon electrode as working electrode,1M Ag-AgCl electrode with large area as reference electrode,0.2M NH4Ac as supporting from -0.5 to +1.2 voltage(vs.M Ag-AgCl).The peak current proportional to the concentration of reducing substances,and the characteristic peak potential of each organic reducing substance were regarded as the quantitative and qualitative base,respectively.These results obtained under the conditions mentioned above directly reflect both the reducing intensity and capacity of the organic reducing system in soils.

  19. Substance Abuse among High-Risk Sexual Offenders: Do Measures of Lifetime History of Substance Abuse Add to the Prediction of Recidivism over Actuarial Risk Assessment Instruments?

    Science.gov (United States)

    Looman, Jan; Abracen, Jeffrey

    2011-01-01

    There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has…

  20. Just say know: an examination of substance use disorders among older adults in gerontological and substance abuse journals.

    Science.gov (United States)

    Rosen, Daniel; Engel, Rafael J; Hunsaker, Amanda E; Engel, Yael; Detlefsen, Ellen Gay; Reynolds, Charles F

    2013-01-01

    This article examines the extent to which studies of alcohol abuse, illicit drug use, and prescription drug abuse among older adults appear in the leading gerontological and substance abuse journals. The authors reviewed articles published in the 10 social science gerontological journals and the 10 social science substance abuse journals with the highest 5-year impact factors in PubMed from 2000 to 2010. Articles were selected that presented original research on alcohol, substance, or prescription abuse with older adults aged 50 and older; and were identified through aging and substance abuse-related Medical Subject Headings and word searches of titles and abstracts (N = 634). Full text of each article was reviewed by the authors, and consensus determined inclusion in the final sample. Of the 19,953 articles published respectively in the top 10 gerontological and substance abuse journals, 181 articles met the inclusion criteria of reporting findings related to substance use disorders among older adults. Specifically, 0.9% (102 of 11,700) of articles from the top 10 gerontology journals and 1.0% (79 of 8,253) of articles from the top 10 substance abuse journals met the criteria. Most published articles addressed alcohol misuse/abuse or polysubstance abuse with few articles addressing illicit drug use or the misuse of prescription medications. Less than 1% of articles published in the 10 gerontology journals and the 10 substance abuse journals with the highest 5-year impact scores addressed substance abuse in older adults. Practitioners treating health and/or mental health problems are at a disadvantage in accurately identifying and treating these conditions in older adult populations without a proper understanding of the role of comorbid substance use disorders.

  1. Life History Strategy and Young Adult Substance Use

    Directory of Open Access Journals (Sweden)

    George B. Richardson

    2014-04-01

    Full Text Available This study tested whether life history strategy (LHS and its intergenerational transmission could explain young adult use of common psychoactive substances. We tested a sequential structural equation model using data from the National Longitudinal Survey of Youth. During young adulthood, fast LHS explained 61% of the variance in overall liability for substance use. Faster parent LHS predicted poorer health and lesser alcohol use, greater neuroticism and cigarette smoking, but did not predict fast LHS or overall liability for substance use among young adults. Young adult neuroticism was independent of substance use controlling for fast LHS. The surprising finding of independence between parent and child LHS casts some uncertainty upon the identity of the parent and child LHS variables. Fast LHS may be the primary driver of young adult use of common psychoactive substances. However, it is possible that the young adult fast LHS variable is better defined as young adult mating competition. We discuss our findings in depth, chart out some intriguing new directions for life history research that may clarify the dimensionality of LHS and its mediation of the intergenerational transmission of substance use, and discuss implications for substance abuse prevention and treatment.

  2. The Role of Spirituality in Treating Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    James DiReda

    2016-08-01

    Full Text Available Prolonged use and abuse of substances (alcohol, cocaine, and/or opiates can often negatively affect the mind, body, and spirit of those individuals who use them, and progress into dependence and addiction. In order to effectively intervene, these same domains (mind, body, and spirit must be addressed during treatment, and be part of the ongoing education and clinical supervision with the staff providing treatment. This article describes the findings of a qualitative Cross-Sectional Survey Design that examines the role and influence of Spirituality on a sample of 50 men and women diagnosed with substance use disorders (addiction, residing in a 30-day residential treatment program. Many treatment programs include information designed to educate individuals on the negative effects of substance use and abuse on the mind, body, and spirit from a variety of perspectives, but provide few practices and little understanding on the spiritual aspects of recovering from substance use disorders. Using an availability sampling method, survey data from 31 residents in treatment for substance use disorders/ addiction was collected. The finding of this study help provide an overview of Spirituality as it relates to the treatment of substance use disorders and addiction, and explain the value of using a Spiritual approach in the treatment of substance use disorders, as reported by the participants of this study.

  3. Emotion dysregulation, anticipatory cortisol, and substance use in urban adolescents.

    Science.gov (United States)

    Kliewer, Wendy; Riley, Tennisha; Zaharakis, Nikola; Borre, Alicia; Drazdowski, Tess K; Jäggi, Lena

    2016-09-01

    Anticipatory cortisol is associated with risk for substance use in adolescents. The present study extended prior literature by testing a model linking family emotional climate, emotion dysregulation, anticipatory cortisol, and substance use. Participants were 229 adolescents (M = 11.94 years, SD = 1.55; 41% male; 92% African American) enrolled in a 4-wave study of stressors, physiological stress responses, and substance use. Caregivers completed measures of family emotional climate at baseline and adolescents' emotion dysregulation one and two years later; adolescents reported on their substance use at baseline and three years later at Wave 4. Adolescents completed a stress task at Wave 4; saliva samples taken immediately prior to the task were analyzed for cortisol. Longitudinal path models revealed that a negative emotional climate at home was associated with elevated emotion dysregulation at subsequent waves for all youth. Emotional dysregulation was prospectively associated with blunted anticipatory cortisol, which in turn was associated with elevated substance use, controlling for baseline substance use and age. However, these associations only were observed for females. This study suggests that helping girls in particular manage their emotional responses to stress more effectively may impact their physiological responses and reduce risk for substance use.

  4. Understanding the diverse needs of children whose parents abuse substances.

    Science.gov (United States)

    Solis, Jessica M; Shadur, Julia M; Burns, Alison R; Hussong, Andrea M

    2012-06-01

    In this review, we consider the potential service needs of children of substance abusing parents based on what we know about the risk outcomes faced by these children and the parenting deficits often present in these families. Importantly, our review does not address the etiological role of parental substance abuse in children's negative outcomes but instead we discuss the complex inter-related risk factors that often co-occur with and exacerbate risk associated with parental alcohol and drug use. We first review studies showing the elevated risk that children of substance abusing parents face in general for poorer academic functioning; emotional, behavioral, and social problems; and an earlier onset of substance use, faster acceleration in substance use patterns, and higher rates of alcohol and drug use disorders. We then review studies showing contextual risk factors for children of substance abusing parents, including parenting deficits (less warmth, responsiveness, and physical and verbal engagement as well as harsher and more over-involved interaction styles), greater risk for child maltreatment, and less secure attachment patterns. We conclude with a discussion of future directions for research and guidelines for professionals working with children and their families where parental substance abuse is present.

  5. A review of substance abuse research in malaysia.

    Science.gov (United States)

    Norliza, C; Norni, A; Anandjit, S; Mohd Fazli, M I

    2014-08-01

    This is a review of research done in the area of substance abuse in Malaysia. There were 109 articles related to substance abuse found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Only 39 articles were reviewed, and case series, case report, reviews and reports were excluded. Research reviewed include the epidemiology of substance abuse, genetics, treatment and its relation to health behaviour, and health management. Studies have shown that more males than females use drugs. There was also a high prevalence of blood-bourne virus diseases and sexually transmitted diseases among drug users. Two studies showed some genetic polymorphism (Cyp 3a4 gene and FAAH Pro129Thr) among heroin and amphetamine users respectively that may contribute to drug dependence. Study on pharmacological treatment for substance abuse were limited to methadone and it was shown to improve the quality of life of heroin dependant patients. Alternative treatments such as acupunture and spiritual approach play a role in the management of substance abuse. Data also showed that treatment centres for substance abuse are lacking facilities for screening, assessment and treatment for medical illness related to substance use, e.g. Hepatitis C and tuberculosis. Studies on the effectiveness of current drug rehabilitation centres were inconclusive.

  6. Trauma Histories, Substance Use Coping, PTSD, and Problem Substance Use Among Sexual Assault Victims

    OpenAIRE

    Ullman, Sarah E.; Relyea, Mark; Peter-Hagene, Liana; Vasquez, Amanda L.

    2013-01-01

    Sexual assault history is associated with higher risk of problem drinking and drug use in women, yet little is known about mechanisms linking trauma histories in general to women’s drinking or drug use problems. This study examined how various types of trauma, substance use coping, and PTSD relate to past-year problem drinking and drug use in women who experienced sexual assault. Data from a large, diverse sample of women who had experienced adult sexual assault was analyzed with structural e...

  7. Research on substances with activity against orthopoxviruses

    Directory of Open Access Journals (Sweden)

    Marcin Kołodziej

    2013-03-01

    Full Text Available Although smallpox was eradicated over 30 years ago, the disease remains a major threat. High mortality, high infectivity and low resistance of the contemporary population make the smallpox virus very attractive to terrorists. The possible presence of illegal stocks of the virus or risk of deliberate genetic modifications cause serious concerns among experts. Hence, it is reasonable to seek effective drugs that could be used in case of smallpox outbreak. This paper reviews studies on compounds with proven in vitro or in vivo antipoxviruses potential, which show various mechanisms of action. Nucleoside analogues, such as cidofovir, can inhibit virus replication. Cidofovir derivatives are developed to improve the bioavailability of the drug. Among the nucleoside analogues under current investigation are: ANO (adenozine N[sub]1[/sub]-oxide and its derivatives, N-methanocarbothymidine [(N-MCT], or derivatitives of aciklovir, peninclovir and brivudin. Recently, ST-246 – which effectively inhibits infection by limiting release of progeny virions – has become an object of attention. It has been also been demonstrated that compounds such as: nigericin, aptamers and peptides may have antiviral potential. An interesting strategy to fight infections was presented in experiments aimed at defining the role of individual genes (E3L, K3L or C6L in the pathogenesis, and looking for their potential blockers. Additionally, among substances considered to be effective in the treatment of smallpox cases, there are factors that can block viral inhibitors of the human complement system, epidermal growth factor inhibitors or immunomodulators. Further studies on compounds with activity against poxviruses are necessary in order to broaden the pool of available means that could be used in the case of a new outbreak of smallpox.

  8. Perfluoroalkyl and polyfluoroalkyl substances in consumer products.

    Science.gov (United States)

    Kotthoff, Matthias; Müller, Josef; Jürling, Heinrich; Schlummer, Martin; Fiedler, Dominik

    2015-10-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are used in a wide range of products of all day life. Due to their toxicological potential, an emerging focus is directed towards their exposure to humans. This study investigated the PFAS load of consumer products in a broad perspective. Perfluoroalkyl sulfonic acids (C4, C6-C8, C10-PFSA), carboxylic acids (C4-C14-PFCA) and fluorotelomer alcohols (4:2, 6:2; 8:2 and 10:2 FTOH) were analysed in 115 random samples of consumer products including textiles (outdoor materials), carpets, cleaning and impregnating agents, leather samples, baking and sandwich papers, paper baking forms and ski waxes. PFCA and PFSA were analysed by HPLC-MS/MS, whereas FTOH were detected by GC/CI-MS. Consumer products such as cleaning agents or some baking and sandwich papers show low or negligible PFSA and PFCA contents. On the other hand, high PFAS levels were identified in ski waxes (up to about 2000 μg/kg PFOA), leather samples (up to about 200 μg/kg PFBA and 120 μg/kg PFBS), outdoor textiles (up to 19 μg/m(2) PFOA) and some other baking papers (up to 15 μg/m(2) PFOA). Moreover, some test samples like carpet and leather samples and outdoor materials exceeded the EU regulatory threshold value for PFOS (1 μg/m(2)). A diverse mixture of PFASs can be found in consumer products for all fields of daily use in varying concentrations. This study proves the importance of screening and monitoring of consumer products for PFAS loads and the necessity for an action to regulate the use of PFASs, especially PFOA, in consumer products.

  9. Perfluoroalkyl substances and food allergies in adolescents.

    Science.gov (United States)

    Buser, Melanie C; Scinicariello, Franco

    2016-03-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are a class of organic compounds that are persistent in the environment due to their stable carbon-fluorine backbone, which is not susceptible to degradation. Research suggests these chemicals may exert an immunotoxic effect. The aim of this study is to investigate the associations between four PFASs - perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) - with food sensitization and food allergies in adolescent participants (ages 12-19years) in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2010, respectively. We performed multivariate logistic regression to analyze the association between individual PFASs with food sensitization (defined as having at least 1 food-specific IgE level≥0.35kU/L) in NHANES 2005-2006 and food allergies (self-reported) in NHANES 2007-2010. Serum PFOA, PFOS, and PFHxS were statistically significantly associated with higher odds to have self-reported food allergies in NHANES 2007-2010. When using IgE levels as a marker of food sensitization, we found that serum PFNA was inversely associated with food sensitization (NHANES 2005-2006). In conclusion, we found that serum levels of PFASs were associated with higher odds to have self-reported food allergies. Conversely, adolescents with higher serum PFNA were less likely to be sensitized to food allergens. These results, along with previous studies, warrant further investigation, such as well-designed longitudinal studies.

  10. 78 FR 38355 - Center for Substance Abuse Prevention; Notice of Meeting

    Science.gov (United States)

    2013-06-26

    ... HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse... and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Prevention (CSAP) Drug..., including specimen characteristics, collection, preparation, and stability; drug analytes, analyte...

  11. Does physical abuse in early childhood predict substance use in adolescence and early adulthood?

    Science.gov (United States)

    Lansford, Jennifer E; Dodge, Kenneth A; Pettit, Gregory S; Bates, John E

    2010-05-01

    Prospective longitudinal data from 585 families were used to examine parents' reports of child physical abuse in the first 5 years of life as a predictor of substance use at ages 12, 16, and 24. Path analyses revealed that physical abuse in the first 5 years of life predicted subsequent substance use for females but not males. We found a direct effect of early physical abuse on girls'substance use at age 12 and indirect effects on substance use at age 16 and age 24 through substance use at age 12. For boys, age 12 substance use predicted age 16 substance use, and age 16 substance use predicted age 24 substance use, but physical abuse in the first 5 years of life was unrelated to subsequent substance use. These findings suggest that for females, a mechanism of influence of early physical abuse on substance use into early adulthood appears to be through precocious initiation of substance use in early adolescence.

  12. 78 FR 45167 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2013-07-26

    ... AGENCY 40 CFR Part 300 National Oil and Hazardous Substances Pollution Contingency Plan; National... appendix of the National Oil and Hazardous Substances Pollution Contingency Plan (NCP). The EPA and the... protection, Air pollution control, Chemicals, Hazardous waste, Hazardous substances,...

  13. 76 FR 30081 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2011-05-24

    ... AGENCY 40 CFR Part 300 National Oil and Hazardous Substances Pollution Contingency Plan; National... (CERCLA) of 1980, as amended, is an appendix of the National Oil and Hazardous Substances Pollution... protection, Air pollution control, Chemicals, Hazardous waste, Hazardous substances,...

  14. 78 FR 49993 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2013-08-16

    ... AGENCY 40 CFR Part 300 National Oil and Hazardous Substances Pollution Contingency Plan; National..., as amended, is an appendix of the National Oil and Hazardous Substances Pollution Contingency Plan... pollution control, Chemicals, Hazardous waste, Hazardous substances, Intergovernmental relations,...

  15. Motivation and Contingency Management Treatments for Substance Use Disorders.

    Science.gov (United States)

    Walter, Kimberly N; Petry, Nancy M

    2016-01-01

    Contingency management (CM) is a highly efficacious psychosocial treatment for substance use disorders based on the principles of behavioral analysis. CM involves delivering a tangible positive reinforcer following objective evidence of submission of a drug-negative urine sample. Although CM interventions primarily involve applying extrinsic rewards, a patient's intrinsic motivation to change substance use behavior may also be impacted by CM. This chapter provides an introduction to CM interventions for substance use disorders and examines the impact of CM on intrinsic motivation . It also addresses applications of this intervention to other conditions and patient populations.

  16. Substance abusers' personality disorders and staff members' emotional reactions

    DEFF Research Database (Denmark)

    Thylstrup, Birgitte; Hesse, Morten

    2008-01-01

    workshops completed a self-report inventory of emotional reactions to patients, the Feeling Word Checklist-58, and substance abusers completed a self-report of DSM-IV personality disorder, the DSM-IV and ICD-10 Personality Disorder Questionnaire. Correlational analysis and multiple regression analysis...... impact on emotional reactions. Conclusion The findings confirm clinical experiences that personality disorder features in patients with substance abuse have an impact on staff members reactions to them. These reactions should be considered in supervision of staff, and in treatment models for patients...... with co-morbid personality disorders and substance abuse....

  17. Isolation of a substance activating foot formation in hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Schaller, H C

    1977-01-01

    We have developed an assay for a substance from hydra that accelerates foot regeneration in the animal. This substance is specific for the foot as evidenced by the following findings: (1) It is present in the animal as a steep gradient descending from foot to head, paralleling the foot-forming po...... be extracted from hydra tissue with methanol and separated from other known morphogens of hydra by gel filtration and ion-exchange chromatography. A substance with similar biological and physicochemical properties can be isolated from sea anemones....

  18. Control of Oxygen Concentration by Using a Carbonaceous Substance

    Directory of Open Access Journals (Sweden)

    Mohanad Jadan

    2005-01-01

    Full Text Available The control of oxygen concentration in gas flow may be used in chemical industry, heat power engineering, ecology, automobile construction and other industrial branches. This control is realized over a broad range of oxygen concentrations. The control of the oxygen concentration is based on passing of gas flow through a measuring cavity of radio spectrometer and measurement of a magnetic resonance signal. A change in the magnetic resonance signal of a dispersed carbonaceous substance, placed into the cavity, indicates to the changes in oxygen concentrations. The dispersed anthracite and thermal treatment cellulose substance in the oxygen-free medium are proposed to use as a carbonaceous substance.

  19. Culturally competent substance abuse treatment with transgender persons.

    Science.gov (United States)

    Nuttbrock, Larry A

    2012-01-01

    Transgender individuals are misunderstood and inadequately treated in many conventional substance abuse treatment programs. This article reviews current concepts regarding the definition and diversity of transgenderism and summarizes the existing literature on the prevalence and correlates of substance use in transgendered populations. Examples of culturally competent and gender-sensitive treatment in specialized settings are cited, with a call to extend these initiatives throughout the gamut of service venues that engage transgender individuals. Cultural competence combined with gender sensitivity should improve the effectiveness of substance abuse treatment for transgender individuals and will contribute to the goal of providing effective services in an increasingly diverse society.

  20. Yoga and substance use disorders: A narrative review.

    Science.gov (United States)

    Sarkar, Siddharth; Varshney, Mohit

    2017-02-01

    Yoga has been utilized for promotion of health and alleviating distress. It has also been used as a therapeutic measure in the field of mental health, including substance use disorders. This narrative review discusses the literature pertaining to use of yoga in the treatment of substance use disorders. The evidence base especially with regards to randomized trials is presented. The possible mechanisms how yoga might be helpful in the treatment of substance use disorders are explored. Subsequently, implications of yoga in clinical practice are elaborated, followed by examination of the issues in interpretation of the literature of published yoga related studies.