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Sample records for thymidine kinase suicide

  1. Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy

    DEFF Research Database (Denmark)

    Khan, Z.; Knecht, Wolfgang; Willer, Mette

    2010-01-01

    The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen...... suicide gene therapy system in combination with stem cell mediated gene delivery promises new treatment of malignant gliomas....... for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient gene transfer to the tumor cells, limited prodrug penetration into the CNS, and inefficient enzymatic activity of the suicide gene. We report here the cloning and successful application of a novel thymidine...

  2. Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene

    International Nuclear Information System (INIS)

    Hlavaty, J.; Hlubinova, K.; Altanerova, V.; Liska, J.; Altaner, C.

    1997-01-01

    The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduced the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C 6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells. (author)

  3. Thymidine uptake, thymidine incorporation, and thymidine kinase activity in marine bacterium isolates

    International Nuclear Information System (INIS)

    Jeffrey, W.H.; Paul, J.H.

    1990-01-01

    One assumption made in bacterial production estimates from [ 3 H]thymidine incorporation is that all heterotrophic bacteria can incorporate exogenous thymidine into DNA. Heterotrophic marine bacterium isolates from Tampa Bay, Fla., Chesapeake Bay, Md., and a coral surface microlayer were examined for thymidine uptake (transport), thymidine incorporation, the presence of thymidine kinase genes, and thymidine kinase enzyme activity. Of the 41 isolates tested, 37 were capable of thymidine incorporation into DNA. The four organisms that could not incorporate thymidine also transported the thymidine poorly and lacked thymidine kinase activity. Attempts to detect thymidine kinase genes in the marine isolates by molecular probing with gene probes made from Escherichia coli and herpes simplex virus thymidine kinase genes proved unsuccessful. To determine if the inability to incorporate thymidine was due to the lack of thymidine kinase, one organism, Vibro sp. strain DI9, was transformed with a plasmid (pGQ3) that contained an E. coli thymidine kinase gene. Although enzyme assays indicated high levels of thymidine kinase activity in transformants, these cells still failed to incorporate exogenous thymidine into DNA or to transport thymidine into cells. These results indicate that the inability of certain marine bacteria to incorporate thymidine may not be solely due to the lack of thymidine kinase activity but may also be due to the absence of thymidine transport systems

  4. Thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine suicide gene therapy-induced cell apoptosis in breast cancer cells.

    Science.gov (United States)

    Kong, H; Tao, L; Qi, K; Wang, Y; Li, Q; Du, J; Huang, Z

    2013-09-01

    The present study was conducted to explore the efficacy of suicide gene therapy with thymidine kinase (TK) in combination with cytosine deaminase (CD) for breast cancer. The expression of CD/TK was detected in the infected cells by RT-PCR. The killing effect on MCF-7 cells following treatment was analyzed by MTT assay. The morphological characteristics of the cells were observed by electron microscopy, and the distribution of the cell cycle was analyzed by flow cytometry. Caspase‑3 and -8 activities were detected by absorption spectrometry. Cytotoxic assays showed that cells transfected with CD/TK became more sensitive to the prodrugs. Morphological features characteristic of apoptosis were noted in the MCF‑7 cells via electron microscopy. The experimental data showed that the proportion of MCF-7 cells during the different phases of the cell cycle varied significantly following treatment with the prodrugs. The activity of caspase‑3 gradually increased following treatment with increasing concentrations of the prodrugs. We conclude that the TK/ganciclovir and CD/5-fluorocytosine suicide gene system used here induces apoptosis in breast cancer cells, and provides a promising treatment modality for breast cancer.

  5. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  6. The development of herpes simplex virus thymidine kinase suicide gene imaging

    International Nuclear Information System (INIS)

    Xing Yan; Zhao Jinhua

    2006-01-01

    Suicide gene treatment of tumor catches more and more attention in recent years. Cells transferred with suicide gene from virus or bacteria will express specific enzymes and transform innocuous prodrugs into highly toxic chemotherapeutic drugs. As a result, the cells will be killed. Radionuclide labeled probe can display the biologic characteristics of suicide gene in vivo. This article reviews the development of HSV-tk gene imaging. (authors)

  7. Tomato thymidine kinase is subject to inefficient TTP feedback regulation

    DEFF Research Database (Denmark)

    Larsen, Nicolai Balle; Munch-Petersen, Birgitte; Piskur, Jure

    2014-01-01

    A promising suicide gene therapy system to treat gliomas has been reported: the thymidine kinase 1 from tomato (toTK1) combined with the nucleoside analog pro-drug zidovudine (azidothymidine, AZT), which is known to penetrate the blood–brain barrier. Transduction with toTK1 has been found...

  8. Thymidine plaque autoradiography of thymidine kinase-positive and thymidine kinase-negative herpesviruses

    International Nuclear Information System (INIS)

    Tenser, R.B.; Jones, J.C.; Ressel, S.J.; Fralish, F.A.

    1983-01-01

    Plaques formed by herpes simplex virus (HSV), pseudorabies virus, and varicella-zoster virus were studied by plaque autoradiography after [ 14 C]thymidine labeling. Standard thymidine kinase-positive (TK+) viruses and TK- mutants of HSV types 1 and 2 and pseudorabies virus were studied, including cell cultured viruses and viruses isolated from animals. Autoradiography was performed with X-ray film with an exposure time of 5 days. After development of films, TK+ plaques showed dark rims due to isotope incorporation, whereas TK- plaques were minimally labeled. Plaque autoradiography of stock TK- viruses showed reversion frequencies to the TK+ phenotype of less than 10(-3). Autoradiography indicated that TK- virus retained the TK- phenotype after replication in vivo. In addition, it was shown that TK- HSV could be isolated from mouse trigeminal ganglion tissue after corneal inoculation of TK- HSV together with TK+ HSV. The plaque autoradiographic procedure was very useful to evaluate proportions of TK+ and TK- virus present in TK+-TK- virus mixtures

  9. Comparative active-site mutation study of human and Caenorhabditis elegans thymidine kinase 1

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Uhlin, Ulla; Munch-Petersen, Birgitte

    2012-01-01

    ligands. To improve our understanding of TK1 substrate specificity, we performed a detailed, mutation-based comparative structure-function study of the active sites of two thymidine kinases: HuTK1 and Caenorhabditis elegans TK1 (CeTK1). Specifically, mutations were introduced into the hydrophobic pocket......'-deoxythymidine (AZT) compared with the natural substrate thymidine. The crystal structure of the T163S-mutated HuTK1 reveals a less ordered conformation of the ligand thymidine triphosphate compared with the wild-type structure but the cause of the changed specificity towards AZT is not obvious. Based on its...... highly increased AZT activity relative to thymidine activity this TK1 mutant could be suitable for suicide gene therapy....

  10. The role of herpes simplex virus-1 thymidine kinase alanine 168 in substrate specificity.

    Science.gov (United States)

    Candice L, Willmon; Django, Sussman; Margaret E, Black

    2008-01-01

    Herpes simplex virus type 1 (HSV) thymidine kinase (TK) has been widely used in suicide gene therapy for the treatment of cancer due to its broad substrate specificity and the inability of the endogenous human TK to phosphorylate guanosine analogs such as ganciclovir (GCV). The basis of suicide gene therapy is the introduction of a gene that encodes a prodrug-activating enzyme into tumor cells. After administration, the prodrug is selectively converted to a toxic drug by the suicide gene product thereby bringing about the eradication of the cancer cells. A major drawback to this therapy is the low activity the enzyme displays towards the prodrugs, requiring high prodrug doses that result in adverse side effects. Earlier studies revealed two HSV TK variants (SR39 and mutant 30) derived by random mutagenesis with enhanced activities towards GCV in vitro and in vivo. While these mutants contain multiple amino acid substitutions, molecular modeling suggests that substitutions at alanine 168 (A168) may be responsible for the observed increase in prodrug sensitivity. To evaluate this, site-directed mutagenesis was used to individually substitute A168 with phenylalanine or tyrosine to reflect the mutations found in SR39 and mutant 30, respectively. Additionally, kinetic parameters and the ability of these mutants to sensitize tumor cells to GCV in comparison to wild-type thymidine kinase were determined.

  11. Mutation Study of Two Thymidine Kinases 

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Munch-Petersen, Birgitte; Eklund, Hans

    that phosphorylates all the natural deoxyribonucleosides and like insects, C. elegans only contains a single deoxyribonucleoside kinase-like gene. In contrast to the insects, however, the protein encoded by the elegans gene is 46 % identical to human TK1 (HuTK1) and have no homology to the insect kinase. Like HuTK1...... the C. elegans kinase (CeTK1) has thymidine as the preferred substrate, but it also displays activity with deoxyguanosine, though with high Km. A number of point mutations have been introduced in the active site of both the human and elegans TK's in order to change the substrate specificity away from...... not phosphorylate the anticancer analog 1-β-D-arabinofuranosylcytosine (AraC), however. The HuTK1 mutant has been crystallized, and azidothymidine monophosphate has been modelled into the active site....

  12. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    Energy Technology Data Exchange (ETDEWEB)

    Slot Christiansen, Louise [Department of Biology, Lund University, Lund 22362 (Sweden); Lund Protein Production Platform, Lund University, Lund 22362 (Sweden); Egeblad, Louise [Lund Protein Production Platform, Lund University, Lund 22362 (Sweden); Munch-Petersen, Birgitte [Department of Science, Systems and Models, Roskilde University, Roskilde 4000 (Denmark); Piškur, Jure [Department of Biology, Lund University, Lund 22362 (Sweden); Knecht, Wolfgang, E-mail: Louise.Slot_Christiansen@biol.lu.se [Department of Biology, Lund University, Lund 22362 (Sweden); Lund Protein Production Platform, Lund University, Lund 22362 (Sweden)

    2015-06-08

    Nucleoside analogues (NA) are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs) as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals and viruses. Newly discovered dNKs have been tested as enzymes for suicide gene therapy. The tomato thymidine kinase 1 (ToTK1) is a dNK that has been selected for its in vitro kinetic properties and then successfully been tested in vivo for the treatment of malignant glioma. We present the selection of two improved variants of ToTK1 generated by random protein engineering for suicide gene therapy with the NA azidothymidine (AZT). We describe their selection, recombinant production and a subsequent kinetic and biochemical characterization. Their improved performance in killing of E. coli KY895 is accompanied by an increase in specificity for the NA AZT over the natural substrate thymidine as well as a decrease in inhibition by dTTP, the end product of the nucleoside salvage pathway for thymidine. The understanding of the enzymatic properties improving the variants efficacy is instrumental to further develop dNKs for use in suicide gene therapy.

  13. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    Directory of Open Access Journals (Sweden)

    Louise Slot Christiansen

    2015-06-01

    Full Text Available Nucleoside analogues (NA are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals and viruses. Newly discovered dNKs have been tested as enzymes for suicide gene therapy. The tomato thymidine kinase 1 (ToTK1 is a dNK that has been selected for its in vitro kinetic properties and then successfully been tested in vivo for the treatment of malignant glioma. We present the selection of two improved variants of ToTK1 generated by random protein engineering for suicide gene therapy with the NA azidothymidine (AZT.We describe their selection, recombinant production and a subsequent kinetic and biochemical characterization. Their improved performance in killing of E. coli KY895 is accompanied by an increase in specificity for the NA AZT over the natural substrate thymidine as well as a decrease in inhibition by dTTP, the end product of the nucleoside salvage pathway for thymidine. The understanding of the enzymatic properties improving the variants efficacy is instrumental to further develop dNKs for use in suicide gene therapy.

  14. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    International Nuclear Information System (INIS)

    Slot Christiansen, Louise; Egeblad, Louise; Munch-Petersen, Birgitte; Piškur, Jure; Knecht, Wolfgang

    2015-01-01

    Nucleoside analogues (NA) are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs) as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals and viruses. Newly discovered dNKs have been tested as enzymes for suicide gene therapy. The tomato thymidine kinase 1 (ToTK1) is a dNK that has been selected for its in vitro kinetic properties and then successfully been tested in vivo for the treatment of malignant glioma. We present the selection of two improved variants of ToTK1 generated by random protein engineering for suicide gene therapy with the NA azidothymidine (AZT). We describe their selection, recombinant production and a subsequent kinetic and biochemical characterization. Their improved performance in killing of E. coli KY895 is accompanied by an increase in specificity for the NA AZT over the natural substrate thymidine as well as a decrease in inhibition by dTTP, the end product of the nucleoside salvage pathway for thymidine. The understanding of the enzymatic properties improving the variants efficacy is instrumental to further develop dNKs for use in suicide gene therapy

  15. Characterization of Oligomeric and Kinetic Properties of Tomato Thymidine Kinase 1

    DEFF Research Database (Denmark)

    Mutahir, Zeeshan; Larsen, Nicolai Balle; Andersson, Karl-Magnus

    2011-01-01

    The gene encoding thymidine kinase 1 from tomato (toTK1) has in combination with azidothymidine (AZT) recently been proposed as a powerful suicide gene for anticancer gene therapy. The toTK1/AZT combination has been demonstrated to have several advantages for the treatment of glioblastomas because...... been shown that human TK1 is a dimer in the absence of ATP and a tetramer if preincubated with ATP. However, we show here that ATP reincubation did not result in a structural shift from dimer to tetramer in toTK1. For human TK1 pretreated with ATP, the Km value decreased 20-fold, but toTK1’s Km value...

  16. Radioimmunoassay for herpes simplex virus (HSV) thymidine kinase

    International Nuclear Information System (INIS)

    McGuirt, P.V.; Keller, P.M.; Elion, G.B.

    1982-01-01

    A sensitive RIA for HSV-1 thymidine kinase (TK) has been developed. This assay is based on competition for the binding site of a rabbit antibody against purified HSV-1 TK, between a purified 3 H-labeled HSV-1 TK and a sample containing an unknown amount of viral TK. The assay is capable of detecting 8 ng or more of the HSV enzyme. Purified HSV-1 TK denatured to <1% of its original kinase activity is as effective in binding to the antibody as is native HSV-1 TK. Viral TK is detectable at ranges of 150-460 ng/mg protein of cell extract from infected cells or cells transformed by HSV or HSV genetic material. HSV-2 TK appears highly cross-reactive, VZV TK is slightly less so, and the vaccinia TK shows little or no cross-reactivity. This RIA may serve as a tool for monitoring the expression of the HSV TK during an active herpes virus infection, a latent ganglionic infection, or in neoplastic cells which may have arisen by viral transformation

  17. Gamma-T4 hybrid bacteriophage carrying the thymidine kinase gene of bacteriophage T4.

    OpenAIRE

    Mileham, A J; Murray, N E; Revel, H R

    1984-01-01

    Among 32 lambda-T4 recombinant phages selected for growth on a thymidylate synthetase-deficient (thyA) host, 2 were shown to carry the T4 thymidine kinase (tk) gene. The lambda-T4tk phages contain two T4 HindIII DNA fragments (2.0 and 1.5 kilobases) that hybridize to restriction fragments of T4 DNA, encompassing the tk locus at 60 kilobases on the T4 map. The T4tk insert compensates for the simultaneous host deficiencies of thymidine kinase and thymidylate synthetase in a thymidine kinase-def...

  18. Retrospective natural history of thymidine kinase 2 deficiency.

    Science.gov (United States)

    Garone, Caterina; Taylor, Robert W; Nascimento, Andrés; Poulton, Joanna; Fratter, Carl; Domínguez-González, Cristina; Evans, Julie C; Loos, Mariana; Isohanni, Pirjo; Suomalainen, Anu; Ram, Dipak; Hughes, M Imelda; McFarland, Robert; Barca, Emanuele; Lopez Gomez, Carlos; Jayawant, Sandeep; Thomas, Neil D; Manzur, Adnan Y; Kleinsteuber, Karin; Martin, Miguel A; Kerr, Timothy; Gorman, Grainne S; Sommerville, Ewen W; Chinnery, Patrick F; Hofer, Monika; Karch, Christoph; Ralph, Jeffrey; Cámara, Yolanda; Madruga-Garrido, Marcos; Domínguez-Carral, Jana; Ortez, Carlos; Emperador, Sonia; Montoya, Julio; Chakrapani, Anupam; Kriger, Joshua F; Schoenaker, Robert; Levin, Bruce; Thompson, John L P; Long, Yuelin; Rahman, Shamima; Donati, Maria Alice; DiMauro, Salvatore; Hirano, Michio

    2018-03-30

    Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. The study was conducted by 42 investigators across 31 academic medical centres. We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase

    International Nuclear Information System (INIS)

    Haberkorn, Uwe; Khazaie, Khashayarsha; Morr, Iris; Altmann, Annette; Mueller, Markus; Kaick, Gerhard van

    1998-01-01

    Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r=0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk

  20. Human cytosolic thymidine kinase: purification and physical characterization of the enzyme from HeLa cells

    International Nuclear Information System (INIS)

    Sherley, J.L.; Kelly, T.J.

    1988-01-01

    The mammalian cytosolic thymidine kinase is one of a number of enzymes involved in DNA replication whose activities increase dramatically during S phase of the cell cycle. As a first step in defining the mechanisms that control the S phase induction of thymidine kinase activity, the authors have purified the human enzyme from HeLa cells and raised a specific immune serum against the purified protein. The enzyme was isolated from cells arrested in S phase by treatment with methotrexate and purified to near homogeneity by ion-exchange and affinity chromatography. Stabilization of the purified enzyme was achieved by the addition of digitonin. An electrophoretic R/sub m/ of 0.2 in nondenaturing gels characterizes the purified enzyme activity as cytosolic thymidine kinase. The enzyme has a Stoke's radius of 40 A determined by gel filtration and a sedimentation coefficient of 5.5 S determined by glycerol gradient sedimentation. Based on these hydrodynamic values, a native molecular weight of 96,000 was calculated for the purified enzyme. When electrophoresed in denaturing sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, the most purified enzyme fraction was found to contain one predominant polypeptide of M/sub r/ = 24,000. Several lines of evidence indicate that this polypeptide is responsible for thymidine kinase enzymatic activity

  1. Dominant negative selection of vaccinia virus using a thymidine kinase/thymidylate kinase fusion gene and the prodrug azidothymidine

    International Nuclear Information System (INIS)

    Holzer, Georg W.; Mayrhofer, Josef; Gritschenberger, Werner; Falkner, Falko G.

    2005-01-01

    The Escherichia coli thymidine kinase/thymidylate kinase (tk/tmk) fusion gene encodes an enzyme that efficiently converts the prodrug 3'-azido-2',3'-dideoxythymidine (AZT) into its toxic triphosphate derivative, a substance which stops DNA chain elongation. Integration of this marker gene into vaccinia virus that normally is not inhibited by AZT allowed the establishment of a powerful selection procedure for recombinant viruses. In contrast to the conventional vaccinia thymidine kinase (tk) selection that is performed in tk-negative cell lines, AZT selection can be performed in normal (tk-positive) cell lines. The technique is especially useful for the generation of replication-deficient vaccinia viruses and may also be used for gene knock-out studies of essential vaccinia genes

  2. [Enzymatic activity of thymidine kinase of herpes simlex virus strain resistant to H-phosphonates of Acv].

    Science.gov (United States)

    Gus'kova, A A; Skoblov, M Iu; Andronova, V L; Galegov, G A; Kochetkov, S N; Skoblov, Iu S

    2011-01-01

    Cloned laboratory mutants of herpes simplex virus type I resistant to acycloguanosine H-phosphonate have been investigated. For all clones were shown that mutations resulted to increasing of sensitivity to acting of sidofovir. Thymidine kinase of mutant viruses partially preserves the ability to phosphorilate thymidine, but loses the ability to phosphorilate BVDU.

  3. Advances in study of perpes simplex virus type 1-thymidine kinase reporter gene imaging

    International Nuclear Information System (INIS)

    Liu Ying; Lan Xiaoli; Zhang Yongxue

    2007-01-01

    Radionuclide reporter gene imaging is an effect way to provide qualitative and quantitative information for gene therapy. There are three systems of reporter gene including kinase reporter gene. perpes simplex virus type 1-thymidine kinase (HSV1-tk) has perfect physical and chemical characteristic which is suit for imaging as reporter gene. It has been widely investigated and intensively researched. Two substrates of HSV1-tk are purine nucleosite derivant and acyclovir derivant, which can also be used as reporter probes of HSV1-tk. (authors)

  4. Tritiated thymidine and deoxycytidine suicide of mouse hemopoietic colony forming cells (CFC)

    International Nuclear Information System (INIS)

    Uyeki, E.M.; Wierzba, K.; Bisel, T.U.

    1981-01-01

    Significant enhancement of tritiated dCyd suicide occurred when unlabelled dThd was added to cultures of mouse monocytic colony-forming cells. Incorporation experiments supported the suicide experiments in that incorporation of tritiated dCyd into DNA was significantly increased. One hundred micromolar dCyd significantly reduced the radiotoxicity of 0.3 μCi of tritiated dThd; incorporation experiments indicated a dose-related reduction in the incorporation of tritiated dThd into DNA with the addition of 1-100 μM unlabelled dCyd. The addition of 1 μM aminopterin reversed the effect of 100 μM deoxycytidine; viz., incorporation of dThd into DNA was 90% of controls. Aminopterin had a similar effect on deoxyuridine reversal of tritiated dThd incorporation into DNA. Aminopterin had no effect on the reduction of tritiated dThd incorporation into DNA due to the addition of 100 μM unlabelled thymidine. Unlabelled ribonucleosides, Urd and Cyd, did not significantly affect the suicide pattern of tritiated dThd or dCyd when they were added to CFC cultures. Unlabelled deoxyribonucleosides, dThd or dCyd, did not significantly affect the suicide pattern of either tritiated Cyd or Urd when they were added to cultures containing tritiated ribonucleosides. Unlabelled Urd or Cyd was effective in reversing the suicide due to tritiated Urd or Cyd. (author)

  5. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Ali, Ashfaq

    2012-01-01

    and AtTK1b catalyze redundant reactions. The results obtained in the present study suggest a crucial role for the salvage of thymidine during early plant development. Sequence data from the present study have been deposited in the EMBL database/GenBank under accession numbers: AT3G07800.1 (AtTK1a), At5G...

  6. Detection of bovine herpesvirus 4 glycoprotein B and thymidine kinase DNA by PCR assays in bovine milk

    NARCIS (Netherlands)

    Wellenberg, G.J.; Verstraten, E.; Belak, S.; Verschuren, S.B.E.; Rijsewijk, F.A.M.; Peshev, R.; Oirschot, van J.T.

    2001-01-01

    A polymerase chain reaction (PCR) assay was developed to detect bovine herpesvirus 4 (BHV4) glycoprotein B (gB) DNA, and a nested-PCR assay was modified for the detection of BHV4 thymidine kinase (TK) DNA in bovine milk samples. To identify false-negative PCR results, internal control templates were

  7. Clinical significance of thymidine kinase in Egyptian children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Adel A Hagag

    2015-01-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1 is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. Objective: To study the clinical significance of TK-1 in children with ALL. Patients and Methods: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. Results: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. Conclusion: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. Recommendations: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors.

  8. Elevation of serum thymidine kinase 1 in a bacterial infection: canine pyometra.

    Science.gov (United States)

    Sharif, H; Hagman, R; Wang, L; Eriksson, S

    2013-01-01

    Pyometra is a bacterial infection of the uterus that is common in dogs and is potentially life-threatening if delayed in diagnosis and/or treatment. Thymidine kinase 1 (TK1) is a cytosolic enzyme involved in DNA precursor synthesis, and it is also present in serum from patients with malignant diseases. TK1 has been used as a cell proliferation biomarker for many years in human medicine and recently in dogs. However, little is known regarding serum TK1 levels in individuals with bacterial infection. The objective of this study was to determine the activity of serum TK1 in dogs with pyometra and compare it with hematologic and biochemical parameters, e.g., acute phase proteins and inflammatory mediators such as C-reactive protein and Prostaglandin F(2α). Serum and plasma TK1 activity of 40 healthy female dogs and 54 dogs with pyometra were analyzed using an optimized [(3)H]-thymidine phosphorylation assay. TK1 activities in serum or plasma were significantly higher in dogs with pyometra as compared with healthy female dogs (mean ± SD: 4.0 ± 7.3 pmol/min/mL in the pyometra group and 1.07 ± 0.34 pmol/min/mL in healthy control group). However, there was no difference in TK1 activity between systemic inflammatory response syndrome (SIRS) positive (n = 38) and SIRS negative (n = 16) pyometra cases. Furthermore, the plasma TK1 activity decreased in six and increased in one pyometra patients (n = 10), 24 h after ovariohysterectomy. No significant correlations (P > 0.05) were found between TK1 activity and hematological or other biochemical parameters. In conclusion, the TK1 activity was significantly elevated in dogs with pyometra. Further studies are needed to evaluate the mechanism and role of serum TK1 activity in bacterial infections and its possible diagnostic or prognostic value. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Identification and nucleotide sequence of the thymidine kinase gene of Shope fibroma virus

    International Nuclear Information System (INIS)

    Upton, C.; McFadden, G.

    1986-01-01

    The thymidine kinase (TK) gene of Shope fibroma virus (SFV), a tumorigenic leporipoxvirus, was localized within the viral genome with degenerate oligonucleotide probes. These probes were constructed to two regions of high sequence conservation between the vaccinia virus TK gene and those of several known eucaryotic cellular TK genes, including human, mouse, hamster, and chicken TK genes. The oligonucleotide probes initially localized the SFV TK gene 50 kilobases (kb) from the right terminus of the 160-kb SFV genome within the 9.5-kb BamHI-HindIII fragment E. Fine-mapping analysis indicated that the TK Gene was within a 1.2-kb AvaI-HaeIII fragment, and DNA sequencing of this region revealed an open reading frame capable of encoding a polypeptide of 187 amino acids possessing considerable homology to the TK genes of the vaccinia, variola, and monkeypox orthopoxviruses and also to a variety of cellular TK genes. Homology matrix analysis and homology scores suggest that the SFV TK gene has diverged significantly from its counterpart members in the orthopoxvirus genus. Nevertheless, the presence of conserved upstream open reading frames on the 5' side of all of the poxvirus TK genes indicates a similarity of functional organization between the orthopoxviruses and leporipoxviruses. These data suggest a common ancestral origin for at least some of the unique internal regions of the leporipoxviruses and orthopoxviruses as exemplified by SFV and vaccinia virus, respectively

  10. Thymidine kinase enzyme selective imaging radiopharmaceutical. {sup 99m}Tc(CO){sub 3}-Ganciclovir

    Energy Technology Data Exchange (ETDEWEB)

    Gedik, B.; Teksoez, S.; Ichedef, C.; Kilcar, A.Y.; Medine, E.I.; Ucar, E. [Ege Univ., Bornova, Izmir (Turkey). Dept. of Nuclear Applications

    2013-03-01

    The aim of this study is to radiolabel Ganciclovir, known as having selective antiviral properties against thymidine kinase, with technetium tricarbonylcore ({sup 99m}Tc(CO){sub 3}{sup +}) and to investigate the biological behavior of this complex in vitro and in vivo. Commercially provided Ganciclovir (GCV) was radiolabeled with {sup 99m}Tc(CO){sub 3}{sup +}. Initially, optimum radiolabeling conditions were determined by analyzing factors such as temperature, pH and time. Quality control of the radiolabeled compound was performed. The radiolabeling yield was found to be 97%. The {sup 99m}Tc(CO){sub 3}-GCV complex also displayed good in vitro stability during the 24 h period. In vitro cell uptake studies showed that the {sup 99m}Tc(CO){sub 3}-GCV complex is highly uptaken in A-549, PC-3, HeLa cell lines according to the control group {sup 99m}Tc(I)-tricarbonyl core. The knowledge gained from in vivo and in vitro studies of {sup 99m}Tc(CO){sub 3}-GCV could contribute to the development of a new HSV1-tk gene imaging agent. (orig.)

  11. Investigation on Cell Proliferation with a New Antibody against Thymidine Kinase 1

    Directory of Open Access Journals (Sweden)

    Naining Wang

    2001-01-01

    Full Text Available The cytosolic thymidine kinase 1 (TK1 is one of the enzymes involved in DNA replication. Based on biochemical studies, TK1 is activated at late G1 of cell cycle, and its activity correlates with the cell proliferation. We have developed a polyclonal anti‐TK1 antibody against a synthetic peptide from the C‐terminus of human TK1. Using this antibody, here we demonstrate the exclusive location of TK1 in the cytoplasm of cells. Cell cycle dependent TK1 expression was studied by simultaneous fluorescence staining for TK1 and bromodeoxyuridine, by using elutriated cells, and by quantitation of the amount TK1 in relation to the cellular DNA content. TK1, which was strongly expressed in the cells in S+G2 period, raised at late G1 and decreased during mitosis. The amount of TK1 increased three folds from late G1 to G2. TK1 positive cells were demonstrated in areas of proliferation activity of various normal and malignant tissues. The new anti‐TK1 antibody works in archival specimens and is a specific marker of cell proliferation.

  12. Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance

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    Alison J. Hugill

    2015-11-01

    Full Text Available Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid, and a double knockout of this gene and thymidine kinase (Tk has been reported to cause renal failure and abnormal immune system regulation. In order to further investigate possible links between abnormal tryptophan catabolism and diabetes and to examine the effect of single Afmid knockout, we have carried out metabolic phenotyping of an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance, although their insulin sensitivity is unchanged in comparison to wild-type animals. This phenotype results from a defect in glucose stimulated insulin secretion and these mice show reduced islet mass with age. No evidence of a renal phenotype was found, suggesting that this published phenotype resulted from loss of Tk expression in the double knockout. However, despite specifically removing only exon 2 of Afmid in our experiments we also observed some reduction of Tk expression, possibly due to a regulatory element in this region. In summary, our findings support a link between abnormal tryptophan metabolism and diabetes and highlight beta cell function for further mechanistic analysis.

  13. Functional Coexpression of HSV-1 Thymidine Kinase and Green Fluorescent Protein: Implications for Noninvasive Imaging of Transgene Expression

    OpenAIRE

    Jacobs, Andreas; Dubrovin, Michael; Hewett, Jeff; Sena-Esteves, Miguel; Tan, Cui-Wen; Slack, Mark; Sadelain, Michele; Breakefield, Xandra O; Tjuvajev, Juri G

    1999-01-01

    Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase (HSV-1-tk) marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp) and HSV-1-tk...

  14. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate.

    OpenAIRE

    Coen, D M; Kosz-Vnenchak, M; Jacobson, J G; Leib, D A; Bogard, C L; Schaffer, P A; Tyler, K L; Knipe, D M

    1989-01-01

    Herpes simplex virus infection of mammalian hosts involves lytic replication at a primary site, such as the cornea, translocation by axonal transport to sensory ganglia and replication, and latent infection at a secondary site, ganglionic neurons. The virus-encoded thymidine kinase, which is a target for antiviral drugs such as acyclovir, is not essential for lytic replication yet evidently is required at the secondary site for replication and some phase of latent infection. To determine the ...

  15. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir

    Directory of Open Access Journals (Sweden)

    Huicong Zhou

    2016-06-01

    Full Text Available The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF and HSV TK/GCV (BF-rTK/GCV. However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy.

  16. Role of the viral and cellular encoded thymidine kinase in the repair of UV-irradiated herpes simplex virus

    International Nuclear Information System (INIS)

    Rainbow, A.J.; McMaster Univ., Hamilton, ON

    1989-01-01

    A strain of herpes simplex type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk + ) gene and a thymidine kinase deficient (tk - ) mutant strain (HSC-1:PTK3B) were used as probes to examine the repair of UV-damaged viral DNA in one tk - (143) and two tk + (R970-5 and AC4) human cell lines. UV survival for each HSC-1 strain was similar for infection of both tk - and tk + cells suggesting that the repair of viral DNA was not dependent on the expression of a functional cellular tk gene. In contrast, UV survival of HSV-1:PTK3B was substantially reduced compared to HSV-1:KOS when infecting all 3 human cell lines, as well as Vero monkey kidney cells and LPM1A mouse cells. Tjese results suggest that the repair of UV-irradiated HSV-1 in lytically infected mammalian cells depends, in part at least, on the expression of the viral encoded tk. (author). 20 refs.; 1 fig

  17. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

    Directory of Open Access Journals (Sweden)

    Jianyong Xiao

    Full Text Available The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV. This effect is reported to be mediated by gap junctional intercellular communication (GJIC, and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA, a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  18. Quantification of thymidine kinase (TK1) mRNA in normal and leukemic cells and investigation of structure-function relatiosnhip of recombinant TK1enzyme

    DEFF Research Database (Denmark)

    Kristensen, Tina

    Thymidine kinase (TK) catalyses the ATP-dependent phosphorylation of thymidine to thymidine monophosphate, which is subsequency phosphorylated to thymidine triphosphate and utilized for DNA synthesis. Human cytosolic TK (TKI) is cell cycle regulated, e.g. the TK1 activity increases sharply at the G...... patients with chronic lymphatic leukemia (CLL). 2: Structure-function relationship of recombinant TKI. In the first part a sensitive method (competitive PCR) for quantification of TKI mRNA was established. The TKI mRNA level was quantified in quiescent lymphocytes from control donors (n = 6...... are characterized as being quiescent, the TK activity was in the same range as in quiescent lymphocytes from control donors. However, quantification of the TKI mRNA level shows that all five CLL patients had a very high level (6 to 22 x IO6 copies mg-’ protein) of TKI mRNA, corresponding to the level in dividing...

  19. Effect of p53 activation on cell growth, thymidine kinase-1 activity, and 3'-deoxy-3'fluorothymidine uptake

    International Nuclear Information System (INIS)

    Schwartz, Jeffrey L.; Tamura, Yasuko; Jordan, Robert; Grierson, John R.; Krohn, Kenneth A.

    2004-01-01

    The use of thymidine (TdR) and thymidine analogs such as 3'-deoxy-3'-fluorothymidine (FLT) as positron emission tomography (PET)-based tracers of tumor proliferation rate is based on the hypothesis that measurement of uptake of these nucleosides, a function primarily of thymidine kinase-1 (TK 1 ) activity, provides an accurate measure of cell proliferation in tumors. Tumor growth is influenced by many factors including the oxygen concentration within tumors and whether tumor cells have been exposed to cytotoxic therapies. The p53 gene plays an important role in regulating growth under both of these conditions. The goal of this study was to investigate the influence of p53 activation on cell growth, TK 1 activity, and FLT uptake. To accomplish this, TK 1 activity, S phase fraction, and the uptake of FLT were determined in plateau-phase and exponentially growing cultures of an isogenic pair of human tumor cell lines in which p53 expression was normal or inactivated by human papilloma virus type 16 E6 expression. Ionizing radiation exposure was used to stimulate p53 activity and to induce alterations in cell cycle progression. We found that exposure of cells to ionizing radiation induced dose-dependent changes in cell cycle progression in both cell lines. The relationship between S phase percentage, TK 1 activity, and FLT uptake were essentially unchanged in the p53-normal cell line. In contrast, TK 1 activity and FLT uptake remained high in the p53-deficient variant even when S phase percentage was low due to a p53-dependent G2 arrest. We conclude that a functional p53 response is required to maintain the normal relationship between TK1 activity and S phase percentage following radiation exposure

  20. F-18-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression : in-vitro comparison with other PET tracers

    NARCIS (Netherlands)

    Buursma, AR; Rutgers, [No Value; Hospers, GAP; Mulder, NH; Vaalburg, W; de Vries, EFJ

    Objective The herpes simplex virus thymidine kinase (HSVtk) gene has frequently been applied as a reporter gene for monitoring transgene expression in animal models. In clinical gene therapy protocols, however, extremely low expression levels of the transferred gene are generally observed.

  1. Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kok, Marleen; Bonfrer, Johannes M.; Korse, Catharina M.; de Jong, Daphne; Kersten, Marie José

    2003-01-01

    Non-Hodgkin's lymphoma (NHL) forms a heterogeneous group of diseases. Tumor markers may help to identify high-risk patients who might benefit from more aggressive therapy. Serum soluble CD27 (sCD27) and thymidine kinase (TK) are potentially valuable markers, since sCD27 has previously been shown to

  2. Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors

    International Nuclear Information System (INIS)

    Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

    2016-01-01

    Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim

  3. Preliminary study of MR diffusion weighted imaging in nude mice models of hepatic Bel7402 tumors after adenovirus-mediated cytosine diaminase-thymidine kinase gene therapy

    International Nuclear Information System (INIS)

    Jiang Xinqing; Chen Liang; Wu Hongzhen; Huang Jingjun; Wei Xinhua; Mo Lei; Yang Ruimeng; Xiao Xiangsheng

    2012-01-01

    Objective: To study the characteristics of DWI in nude mice models of hepatic Bel7402 tumors after treatment with adenovirus-mediated cytosine diaminase-thymidine kinase (Ad. CD-TK) double suicide gene therapy, and then to identify whether DWI can be used for assessing curative effect of postoperative tumors. Methods: Thirty nude mice models of hepatic Bel7402 tumors were successfully created using cell suspension method, after the tumor grew to more than 1 cm in diameter, 20 tumor models were treated by intratumoral administration of Ad. CD-TK for 3 days plus intraperitonea (i.p.) treatment with 5-Fc and GCV for the duration of the study.Then they were randomly divided into three groups during 5-Fc and GCV treatment. The remaining 10 tumor models were used as controls. MR scanning were performed in 10 th day before and after tumor implantation in all models by using EPI-SE series and SENSE technology for treatment group. Tumor volumes and ADC values were calculated pretreatment and posttreatment. Cell apoptosis were determined by using TUNEL method. Analyze the change of ADC and apoptosis index (AI) in different times, t test was used for comparison the difference of AI and ADC values respectively. Results: After 10 days,the tumor volumes of the treatment groups and controls were respectively (724.16 ±57.45) mm 3 , (754.57 ± 66.84) mm 3 , with no significant difference (t=0.488, P >0.05). The ADC values of the treatment groups were (0.98 ±0.11) × 10 -3 mm 2 /s,the ones of the control groups were (0.68 ±0.04) × 10 -3 mm 2 /s; AI of the treatment groups were (23.25 ±6.57)%, the ones of the control groups were (2.57 ± 0.58)%. There were difference in both groups (t=4.473, 5.874; P<0.01). Conclusion: DWI can be effectively to monitor the early pathological changes of hepatic Bel7402 tumors after Ad. CD-TK double suicide gene therapy, and provide experimental evidences for clinical application. (authors)

  4. The thymidine kinase-1 as a potential tumor marker: structure, function, activity in normal and malignant tissues

    Directory of Open Access Journals (Sweden)

    N. S. Sergeeva

    2017-01-01

    Full Text Available In the review the role of the thymidine kinase (TK to ensure the replication of DNA de novo and spare (salvage the way in health and activate alternate ways in carcinogenesis is described. The structure of cytoplasmic TK (TК-1, also called fetal, and the level of regulation of its activity in the cells and their change during the cell cycle is described. Considering the data about the absence of TK-1 in resting (G0 cells, TK-1 is positioned as a marker of proliferating cells, which activity is recorded from late G1 phase, peaking in S-phase, it is stored in the G2 and mitosis, quickly decreasing to undetectable levels in the early G1 phase. Data on the expression TK-1 (as compared with Ki-67 and PCNA (proliferating cell nuclear antigen in tumor tissues (colorectal, breast, cervical, lung, renal, prostate and ovarian cancer, as well as some benign and precancerous pathological processes in relation to the clinical and diagnostic features of these processes are systemized. These data suggest that the proliferative index studies on TK-1 (antibody to the domain HRA-210 should be used together with Ki-67 and PCNA, for a more complete assessment of the proliferative status of malignant tumors and pre-cancerous and benign conditions, with the aim of prognosis of the tumor process and treatment planning.

  5. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H

    1994-01-01

    By performing DNase I footprint analysis, we had identified three distinct protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee, A.B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1157-1161). Here we...... report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes....... (iii) Formation of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase-specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es) (E2F.S), whereas "free" E2F increased after the G1/S transition. (iv) Pulse inhibition of protein synthesis with cycloheximide...

  6. Cloning of the koi herpesvirus (KHV gene encoding thymidine kinase and its use for a highly sensitive PCR based diagnosis

    Directory of Open Access Journals (Sweden)

    Gilad Oren

    2005-03-01

    Full Text Available Abstract Background Outbreaks with mass mortality among common carp Cyprinus carpio carpio and koi Cyprinus carpio koi have occurred worldwide since 1998. The herpes-like virus isolated from diseased fish is different from Herpesvirus cyprini and channel catfish virus and was accordingly designated koi herpesvirus (KHV. Diagnosis of KHV infection based on viral isolation and current PCR assays has a limited sensitivity and therefore new tools for the diagnosis of KHV infections are necessary. Results A robust and sensitive PCR assay based on a defined gene sequence of KHV was developed to improve the diagnosis of KHV infection. From a KHV genomic library, a hypothetical thymidine kinase gene (TK was identified, subcloned and expressed as a recombinant protein. Preliminary characterization of the recombinant TK showed that it has a kinase activity using dTTP but not dCTP as a substrate. A PCR assay based on primers selected from the defined DNA sequence of the TK gene was developed and resulted in a 409 bp amplified fragment. The TK based PCR assay did not amplify the DNAs of other fish herpesviruses such as Herpesvirus cyprini (CHV and the channel catfish virus (CCV. The TK based PCR assay was specific for the detection of KHV and was able to detect as little as 10 fentograms of KHV DNA corresponding to 30 virions. The TK based PCR was compared to previously described PCR assays and to viral culture in diseased fish and was shown to be the most sensitive method of diagnosis of KHV infection. Conclusion The TK based PCR assay developed in this work was shown to be specific for the detection of KHV. The TK based PCR assay was more sensitive for the detection of KHV than previously described PCR assays; it was as sensitive as virus isolation which is the golden standard method for KHV diagnosis and was able to detect as little as 10 fentograms of KHV DNA corresponding to 30 virions.

  7. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  8. Functional Coexpression of HSV-1 Thymidine Kinase and Green Fluorescent Protein: Implications for Noninvasive Imaging of Transgene Expression

    Directory of Open Access Journals (Sweden)

    Andreas Jacobs

    1999-06-01

    Full Text Available Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase (HSV-1-tk marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp and HSV-1-tk genes was generated (tkgfp gene and assessed for the functional coexpression of the gene product, TKGFP fusion protein, in rat 9L gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein demonstrated that it can serve as a therapeutic gene by rendering tkgfp transduced cells sensitive to ganciclovir or as a screening marker useful for identifying transduced cells by fluorescence microscopy or fluorescence-activated cell sorting (FACS. TK and GFP activities in the TKGFP fusion protein were similar to corresponding wild-type proteins and accumulation of the HSV-1-tk-specific radiolabeled substrate, 2′-fluoro-2′-deoxy-1β-D-arabino-furanosyl-5-iodo-uracil (FIAU, in stability transduced clones correlated with gfp-fluorescence intensity over a wide range of expression levels. The tkgfp fusion gene itself may be useful in developing novel cancer gene therapy approaches. Valuable information about the efficiency of gene transfer and expression could be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical imaging devices (gamma camera, positron-emission tomography [PET], single photon emission computed tomography [SPECT], and/or direct visualization of gfp expression in situ by fluorescence microscopy or endoscopy.

  9. Expression of herpes simplex virus type 1 recombinant thymidine kinase and its application to a rapid antiviral sensitivity assay.

    Science.gov (United States)

    Shiota, Tomoyuki; Lixin, Wang; Takayama-Ito, Mutsuyo; Iizuka, Itoe; Ogata, Momoko; Tsuji, Masanori; Nishimura, Hidekazu; Taniguchi, Shuichi; Morikawa, Shigeru; Kurane, Ichiro; Mizuguchi, Masashi; Saijo, Masayuki

    2011-08-01

    Antiviral-resistant herpesvirus infection has become a great concern for immunocompromised patients. Herpes simplex virus type 1 (HSV-1) infections are treated with viral thymidine kinase (vTK)-associated drugs such as acyclovir (ACV), and most ACV-resistance (ACV(r)) is due to mutations in the vTK. The standard drug sensitivity test is usually carried out by the plaque reduction assay-based method, which requires over 10 days. To shorten the time required, a novel system was developed by the concept, in which 293T cells transiently expressing recombinant vTK derived from the test sample by transfection of the cells with an expression vector were infected with vTK-deficient and ACV(r) HSV-1 (TAR), and then cultured in a maintenance medium with or without designated concentrations of ACV, ganciclovir (GCV) and brivudine (BVdU). The replication of TAR was strongly inhibited by ACV, GCV and BVdU in 293T cells expressing recombinant vTK of the ACV-sensitive HSV-1, whereas replication was not or slightly inhibited in cells expressing the recombinant vTK of highly resistant or intermediately resistant HSV-1, respectively. An inverse correlation was demonstrated in the 50% effective concentrations (EC(50)s) and inhibitory effects of these compounds on the replication of TAR among ACV(s) and ACV(r) HSV-1 clones. These results indicate that the EC(50)s of the vTK-associated drugs including ACV can be assumed by measuring the inhibitory effect of drugs in 293T cells expressing recombinant vTK of the target virus. The newly developed antiviral sensitivity assay system for HSV-1 makes it possible to estimate EC(50) for vTK-associated drugs, when whole vTK gene is available for use by gene amplification directly from lesion's samples or from virus isolates. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Transfer of herpes simplex virus thymidine kinase synthesized in bacteria by a high-expression plasmid to tissue culture cells by protoplast fusion

    International Nuclear Information System (INIS)

    Waldman, A.S.; Milman, G.

    1984-01-01

    The introduction of a protein into living tissue culture cells may permit the in vivo study of functions of the protein. The authors have previously described a high-efficiency-expression plasmid, pHETK2, containing the herpes simplex virus type 1 thymidine kinase (TK) gene which, upon temperature induction, causes TK to be synthesized as greater than 4% of the bacterial protein. In this report it is shown that enzymatically active TK was transferred to mouse Ltk- cells by polyethylene glycol-mediated fusion with protoplasts prepared from bacteria containing induced levels of TK. The presence of TK in the Ltk- cells was detected by the incorporation of [ 3 H]thymidine into cell nuclei as measured by autoradiography

  11. A multisubstrate deoxyribonucleoside kinase from plants

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Knecht, Wolfgang

    2008-01-01

    and biochemical properties suggest that this deoxyribonucleoside kinase represents a living fossil resembling the progenitor of the modern animal deoxycytidine, deoxyguanosine and thymidine 2 kinases. The broad substrate specificity makes this enzyme an interesting candidate to be evaluated as a suicide gene...

  12. Role of Genotypic Analysis of the Thymidine Kinase Gene of Herpes Simplex Virus for Determination of Neurovirulence and Resistance to Acyclovir

    OpenAIRE

    Lee, N. Y.; Tang, Y.-W.; Espy, M. J.; Kolbert, C. P.; Rys, P. N.; Mitchell, P. S.; Day, S. P.; Henry, S. L.; Persing, D. H.; Smith, T. F.

    1999-01-01

    Mutations in the thymidine kinase (TK) gene of herpes simplex virus (HSV) have been associated with resistance to acyclovir (ACY) and possible recognition of neurotropic strains. We sequenced a 335-bp segment of the TK gene to determine the frequency of mutations in HSV strains recovered from dermal, genital, and cerebrospinal fluid (CSF) specimens (n = 200; 102 HSV type 1 [HSV-1] 98 HSV-2 strains). Four polymorphic sites were detected in HSV-1 strains; C513T, A528G, C575T, and C672T. Among t...

  13. A recombinant bovine herpesvirus 5 defective in thymidine kinase and glycoprotein E is attenuated and immunogenic for calves

    Directory of Open Access Journals (Sweden)

    Deniz Anziliero

    2011-01-01

    Full Text Available Bovine herpesvirus 5 (BoHV-5 is an important pathogen of cattle in South America and efforts have been made to produce safer and more effective vaccines. In addition to afford protection, herpesvirus vaccines should allow serological differentiation of vaccinated from naturally, latently infected animals. We previously reported the construction and characterization in vitro of a double mutant BoHV-5 (BoHV-5gE/TK Δ lacking the genes encoding thymidine kinase (tk for attenuation, and glycoprotein E (gE as the antigenic marker, as a vaccine candidate strain (Brum et al. 2010a. The present article reports an investigation on the attenuation and immunogenicity of this recombinant in calves. In a first experiment, 80 to 90-day-old seronegative calves (n=6 inoculated intranasally with the recombinant (titer of 10(7.5TCID50 shed virus in low to moderate titers in nasal secretions for up to 6 days, yet did not develop any respiratory, systemic or neurological signs of infection. At day 30 post-infection (pi all calves had BoHV-5 specific neutralizing (VN antibodies in titers of 4 to 8 and were negative for anti-gE antibodies in a commercial ELISA test. Administration of dexamethasone (0.1mg/kg/day during 5 days to four of these calves at day 42 pi did not result in virus shedding or increase in VN titers, indicating lack of viral reactivation. Secondly, a group of 8-month-old calves (n=9 vaccinated intramuscularly (IM with the recombinant virus (10(7.5TCID50/animal did not shed virus in nasal secretions, remained healthy and developed VN titers from 2 to 8 at day 42 post-vaccination (pv, remaining negative for gE antibodies. Lastly, 21 calves (around 10 months old maintained under field conditions were vaccinated IM with the recombinant virus (titer of 10(7.3TCID50. All vaccinated animals developed VN titers from 2 to 16 at day 30 pv. A boost vaccination performed at day 240 pv resulted in a rapid and strong anamnestic antibody response, with VN titers

  14. Reduction of fatal graft-versus-host disease by 3H--thymidine suicide of donor cells cultured with host cells

    International Nuclear Information System (INIS)

    Cheever, M.A.; Einstein, A.B. Jr.; Kempf, R.A.; Fefer, A.

    1977-01-01

    The effect of the tritiated thymidine ( 3 H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2/sup b/) spleen cells were stimulated in vitro with irradiated BALB/c (H-2/sup d/) Moloney lymphoma cells in mixed culture and 3 H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 percent) than did C57BL/6 cells cultured with BALB/c lymphoma cells but without 3 H-TdR (87 percent) and C57BL/6 cells cultured with irradiated C57BL/6 cells with (95 percent) or without 3 H-TdR (86 percent). Thus, the 3 H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD

  15. Effect of p53 activation on cell growth, thymidine kinase-1 activity, and 3'-deoxy-3'fluorothymidine uptake

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Jeffrey L. E-mail: jschwart@u.washington.edu; Tamura, Yasuko; Jordan, Robert; Grierson, John R.; Krohn, Kenneth A

    2004-05-01

    The use of thymidine (TdR) and thymidine analogs such as 3'-deoxy-3'-fluorothymidine (FLT) as positron emission tomography (PET)-based tracers of tumor proliferation rate is based on the hypothesis that measurement of uptake of these nucleosides, a function primarily of thymidine kinase-1 (TK{sub 1}) activity, provides an accurate measure of cell proliferation in tumors. Tumor growth is influenced by many factors including the oxygen concentration within tumors and whether tumor cells have been exposed to cytotoxic therapies. The p53 gene plays an important role in regulating growth under both of these conditions. The goal of this study was to investigate the influence of p53 activation on cell growth, TK{sub 1} activity, and FLT uptake. To accomplish this, TK{sub 1} activity, S phase fraction, and the uptake of FLT were determined in plateau-phase and exponentially growing cultures of an isogenic pair of human tumor cell lines in which p53 expression was normal or inactivated by human papilloma virus type 16 E6 expression. Ionizing radiation exposure was used to stimulate p53 activity and to induce alterations in cell cycle progression. We found that exposure of cells to ionizing radiation induced dose-dependent changes in cell cycle progression in both cell lines. The relationship between S phase percentage, TK{sub 1} activity, and FLT uptake were essentially unchanged in the p53-normal cell line. In contrast, TK{sub 1} activity and FLT uptake remained high in the p53-deficient variant even when S phase percentage was low due to a p53-dependent G2 arrest. We conclude that a functional p53 response is required to maintain the normal relationship between TK1 activity and S phase percentage following radiation exposure.

  16. Kinetic and photochemical studies and alteration of ultraviolet sensitivity of Escherichia coli thymidine kinase of halogenated allosteric regulators and substrate analogues

    International Nuclear Information System (INIS)

    Chen, M.S.; Prusoff, W.H.

    1977-01-01

    The effect of various halogenated and nonhalogenated allosteric effectors on the sensitivity of Escherichia coli thymidine kinase to ultraviolet radiations (uv,253.7 nm) was investigated. All naturally occurring dNTPs convert the monomeric form of the enzyme into the dimeric form which is less sensitive to uv inactivation. Whereas 5-iodo-2'-deoxycytidine triphosphate (IdCTP) and 5-iodo-2' deoxyuridine triphosphate (IdUTP) enhance the uv inactivation of the enzyme, 5-bromo-2'-deoxyuridine triphosphate and 5-bromo-2'-deoxycytidine triphosphate exert a protective effect similar to that produced by the corresponding naturally occurring effectors, dTTP and dCTP. The enhanced uv inactivation by IdUTP is prevented totally by dTTP, but only partially by dCTP or dThd, whereas the enhanced sensitization by IdCTP is prevented almost totally by dCTP, partially by dTTP, and not at all by dThd. The uv sensitization of thymidine kinase by IdCTP appears to be at the regulatory site since a maximum saturation effect is observed, and the concentration required to exert a 50% maximal uv sensitization is similar to its K/sub m/ for enhancement of catalytic activity. When the enzyme was irradiated in the presence of either [2- 14 C]IdUTP or [2- 14 C]IdUrd, zone sedimentation analysis in sucrose density gradients showed the sedimentation coefficient of the radioactive labeled proteins to be the same, 3.8 S. Hence uv irradiation of the effector-induced dimer resulted in not only dissociation to the monomer, but also complete loss of catalytic activity. The substitution of an azido group for the 5'-OH group of 5-iodo-, 5-bromo-, 5-chloro-, or 5-fluorodeoxyuridine greatly decreased their affinity for thymidine kinase, and in addition the kinetics of inhibition changed from a competitive to a noncompetitive pattern. The presence of the azido moiety in the 5' position of the halogenated nucleosides did not enhance the rate of uv inactivation of the enzyme

  17. Synthesis and Biological Evaluation of a New Acyclic Pyrimidine Derivative as a Probe for Imaging Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression

    Directory of Open Access Journals (Sweden)

    Simon M. Ametamey

    2013-07-01

    Full Text Available With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk gene expression by means of positron emission tomography (PET, a novel [18F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethylbutyl side chain at N-1 (HHB-5-[18F]FEP was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[18F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [18F]fluoride-cryptate complex in 45% ± 4 (n = 4 radiochemical yields and high purity (>99%. The biological evaluation indicated the feasibility of using HHB-5-[18F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.

  18. Evidence for an involvement of thymidine kinase in the excision repair of ultraviolet-irradiated herpes simplex virus in human cells

    International Nuclear Information System (INIS)

    Intine, R.V.; Rainbow, A.J.

    1990-01-01

    A wild-type strain of herpes simplex virus type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk+) and a tk- mutant strain (HSV-1:PTK3B) were used to study the role of the viral tk in the repair of UV-irradiated HSV-1 in human cells. UV survival of HSV-1:PTK3B was substantially reduced compared with that of HSV-1:KOS when infecting normal human cells. In contrast, the UV survival of HSV-1:PTK3B was similar to that of HSV-1:KOS when infecting excision repair-deficient cells from a xeroderma pigmentosum patient from complementation group A. These results suggest that the repair of UV-irradiated HSV-1 in human cells depends, in part at least, on expression of the viral tk and that the repair process influenced by tk activity is excision repair or a process dependent on excision repair

  19. In vivo PET imaging with 18F-FHBG of hepatoma cancer gene therapy using herpes simplex virus thymidine kinase and ganciclovir

    International Nuclear Information System (INIS)

    Lee, TaeSup; Kim, JunYoup; Moon, ByungSeok; Kang, JooHyun; Song, Inho; Kwon, HeeChung; Kim, KyungMin; Cheon, GiJeong; Choi, ChangWoon; Lim, SangMoo

    2007-01-01

    Monitoring gene expression in vivo to evaluate the gene therapy efficacy is a critical issue for scientists and physicians. Non-invasive nuclear imaging can offer information regarding the level of gene expression and its location when an appropriate reporter gene is constructed in the therapeutic gene therapy. Herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) is the most common reporter gene and is used in cancer gene therapy by activating relatively nontoxic compounds, such as acyclovir or ganciclovir (GCV), to induce cell death. In this study, we investigate the feasibility of monitoring cancer gene therapy using retroviral vector transduced HSV1-tk and GCV, in vitro cellular uptake and in vivo animal studies, including biodistribution and small animal positron emission tomography (PET) imaging, were performed in HSV1-tk and luciferase (Luc)-transduced MCA-TK/Luc and enhanced green fluorescent protein (eGFP)-transduced MCA-eGFP hepatoma cell lines

  20. Thymidine kinase deficient human cells have increased UV sensitivity in their capacity to support herpes simplex virus but normal UV sensitivity for colony formation

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1989-01-01

    A thymidine kinase deficient (tk - ) and two thymidine kinase proficient (tk + ) human cell lines were compared for UV sensitivity using colony-forming ability as well as their capacity to support the plaque formation of herpes simplex type 1 (HSV-1).The tk - line (143 cells) was a derivative of one of the tk + lines (R970-5), whereas the other tk + line (AC4 cells) was a derivative of the 143 cells obtained by transfection with purified sheared HSV-2 DNA encoding the viral tk gene. 143, R970-5 and AC4 cells showed a similar UV sensitivity for colony-forming ability. In contrast, the capacity to support HSV-1 plaque formation immediately (within 1 h) afte UV-irradiation was reduced to a greater extent in the 143 cells compared to the R970-5 and AC4 cells. Capacity curves for plaque formation of the HSV-1: KOS wild-type (tk + ) strain were similar to those for the HSV-1: PTK3B mutant (tk - ) strain were similar to those for the HSV-1: PTK3B mutant (tk - ) strain in the 3 cell strains, indicating that the viral tk gene does not influence the ability of HSV-1 to form plaques in UV-irradiated compared to unirradiated human cells. Cellular capacity for HSV-1 plaque formation was found to recover in both tk - and tk + cells for cultures infected 24 h after UV-irradiation. These results suggest that repair of UV-damaged DNA takes place to a similar extent in both tk - and tk + human cells, but the kinetics of repair are initially slower in tk - compared to tk + human cells. (author). 33 refs.; 3 figs.; 1 tab

  1. Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity

    Energy Technology Data Exchange (ETDEWEB)

    Villarroya, Joan, E-mail: joanvillarroya@gmail.com [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Institut de Recerca l' Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Lara, Mari-Carmen [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Department of Neurology, Columbia University Medical Center, New York, NY (United States); Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII (Spain); Dorado, Beatriz [Department of Neurology, Columbia University Medical Center, New York, NY (United States); Garrido, Marta [Unitat de Biologia Cel.lular i Molecular, IMIM-Hospital del Mar, Barcelona (Spain); Garcia-Arumi, Elena [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII (Spain); Meseguer, Anna [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Hirano, Michio [Department of Neurology, Columbia University Medical Center, New York, NY (United States); Vila, Maya R. [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain)

    2011-04-08

    Highlights: {yields} We impaired TK2 expression in Ost TK1{sup -} cells via siRNA-mediated interference (TK2{sup -}). {yields} TK2 impairment caused severe mitochondrial DNA (mtDNA) depletion in quiescent cells. {yields} Despite mtDNA depletion, TK2{sup -} cells show high cytochrome oxidase activity. {yields} Depletion of mtDNA occurs without imbalance in the mitochondrial dNTP pool. {yields} Nuclear-encoded ENT1, DNA-pol {gamma}, TFAM and TP gene expression is lowered in TK2{sup -} cells. -- Abstract: The mitochondrial DNA (mtDNA) depletion syndrome comprises a clinically heterogeneous group of diseases characterized by reductions of the mtDNA abundance, without associated point mutations or rearrangements. We have developed the first in vitro model to study of mtDNA depletion due to reduced mitochondrial thymidine kinase 2 gene (TK2) expression in order to understand the molecular mechanisms involved in mtDNA depletion syndrome due to TK2 mutations. Small interfering RNA targeting TK2 mRNA was used to decrease TK2 expression in Ost TK1{sup -} cells, a cell line devoid of endogenous thymidine kinase 1 (TK1). Stable TK2-deficient cell lines showed a reduction of TK2 levels close to 80%. In quiescent conditions, TK2-deficient cells showed severe mtDNA depletion, also close to 80% the control levels. However, TK2-deficient clones showed increased cytochrome c oxidase activity, higher cytochrome c oxidase subunit I transcript levels and higher subunit II protein expression respect to control cells. No alterations of the deoxynucleotide pools were found, whereas a reduction in the expression of genes involved in nucleoside/nucleotide homeostasis (human equilibrative nucleoside transporter 1, thymidine phosphorylase) and mtDNA maintenance (DNA-polymerase {gamma}, mitochondrial transcription factor A) was observed. Our findings highlight the importance of cellular compensatory mechanisms that enhance the expression of respiratory components to ensure respiratory activity

  2. Fusion of herpes simplex virus thymidine kinase to VP22 does not result in intercellular trafficking of the protein

    NARCIS (Netherlands)

    Beerens, A. M. J.; Rots, M. G.; de Vries, E. F. J.; Haisma, H. J.

    Suicide gene therapy is a promising approach for the treatment of cancer. Current protocols, however, suffer from low efficiency. We tried to alleviate this problem by developing a transgene that will spread from the initially transduced cell to the surrounding cells (transmission). We used herpes

  3. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Egeblad, Louise; Munch-Petersen, Birgitte

    2015-01-01

    Nucleoside analogues (NA) are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs) as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals and viruses. Newly discovered dNKs have been t...

  4. Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

    Science.gov (United States)

    Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina

    2013-11-01

    Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

  5. Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents

    International Nuclear Information System (INIS)

    Jae, Ho Kim; Sang, Hie Kim; Kolozsvary, Andrew; Brown, Stephen L.; Ok, Bae Kim; Freytag, Svend O.

    1995-01-01

    Purpose: To demonstrate in a well-characterized tumor model that the radiosensitivity of tumor cells transduced with a herpes simplex virus thymidine kinase gene (HS-tk) would be selectively enhanced by antiviral agents. Methods and Materials: Rat 9L gliosarcoma cells transduced with a retroviral vector containing an HS-tk gene, 9L-tk cells were exposed to various doses of irradiation under either in vitro or in vivo conditions. The radiation sensitizing potential of two antiviral drugs, bromovinyl deoxyuridine (BVdU) and dihydroxymethyl ethyl methyl guanine (acyclovir), was evaluated in vitro. The radiosensitizing ability of BVdU was also evaluated with a 9L-tk tumor growing in the rat brain. Tumors growing in the right hemisphere of rat brains were irradiated stereotactically with single-dose irradiation. Results: The radiation response of 9L-tk cells was selectively enhanced by antiviral agents relative to nontransduced cells. In the cell culture, when a 24-h drug exposure (20 μg/ml) preceded radiation, the sensitizer enhancement ratio (SER) for BVdU and acyclovir was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. Exposure of cells to 10 μg/ml acyclovir for two 24-h periods both pre- and postirradiation resulted in a SER of 1.6 ± 0.1. In vivo, a significant increase in median survival time of rats with 9L-tk tumors was found when BVdU was administered prior to single-dose irradiation relative to the survival time of similar rats receiving radiation alone. Conclusion: An antiviral agent can enhance cell killing by radiation with selective action in cells transduced with the herpes simplex virus thymidine kinase gene. The results suggest that the three-pronged therapy of HS-tk gene transduction, systemically administered antiviral drug, and stereotactically targeted radiation therapy will improve the effectiveness of radiation therapy for the treatment of radioresistant tumors

  6. Genotypic and phenotypic characterization of the thymidine kinase of ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus type 1 strain.

    Science.gov (United States)

    Saijo, Masayuki; Suzutani, Tatsuo; De Clercq, Erik; Niikura, Masahiro; Maeda, Akihiko; Morikawa, Shigeru; Kurane, Ichiro

    2002-12-01

    Twenty-four strains of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) were generated from the HSV-1 TAS strain by exposure to ACV, and the genotype and phenotype of the thymidine kinase (TK) from these mutants were analyzed. The TK polypeptide of the ACV(r) HSV-1 strains was examined by Western blot using an anti-HSV-1 TK rabbit serum. The sensitivity of each strain to ACV, foscarnet and cidofovir (CDV) was also determined. A single guanine (G) insertion or a single cytosine (C) deletion was detected in 12 of the 24 ACV(r) strains at the G or C homopolymer stretches within the TK gene. Genotypic analysis predicted that two thirds of the ACV(r) HSV-1 strains expressed truncated TK polypeptides, while one third expressed viral TK polypeptide with a single amino acid substitution at various sites. Western blot abnormalities in the viral TK polypeptides were identified in 21 ACV(r) strains. There was an inverse correlation between the susceptibility of the HSV-1 mutant strains to ACV and that to CDV. Nucleotide sequencing of the TK gene and Western blot analysis of the viral TK polypeptides are considered to be one of the methods for predicting virus sensitivity to ACV and CDV.

  7. Immune responses to recombinants of the South African vaccine strain of lumpy skin disease virus generated by using thymidine kinase gene insertion.

    Science.gov (United States)

    Wallace, David B; Viljoen, Gerrit J

    2005-04-27

    The South African vaccine strain of lumpy skin disease virus (type SA-Neethling) is currently being developed as a vector for recombinant vaccines of economically important livestock diseases throughout Africa. In this study, the feasibility of using the viral thymidine kinase gene as the site of insertion was investigated and recombinant viruses were evaluated in animal trials. Two separate recombinants were generated and selected for homogeneity expressing either the structural glycoprotein gene of bovine ephemeral fever virus (BEFV) or the two structural glycoprotein genes of Rift Valley fever virus (RVFV). Both recombinants incorporate the enhanced green fluorescent protein (EGFP) as a visual marker and the Escherichia coli guanine phosphoribosyl transferase (gpt) gene for dominant positive selection. The LSDV-RVFV recombinant construct (rLSDV-RVFV) protected mice against virulent RVFV challenge. In a small-scale BEFV-challenge cattle trial the rLSDV-BEFV construct failed to fully protect the cattle against virulent challenge, although both a humoral and cellular BEFV-specific immune response was elicited.

  8. Tissue-Specific Expression of Herpes Simplex Virus Thymidine Kinase Gene Delivered by Adeno-Associated Virus Inhibits the Growth of Human Hepatocellular Carcinoma in Athymic Mice

    Science.gov (United States)

    Su, Hua; Lu, Ronghua; Chang, Judy C.; Kan, Yuet Wai

    1997-12-01

    About 70% of hepatocellular carcinomas are known to express α -fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the α -fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

  9. A bovine herpesvirus 5 recombinant defective in the thymidine kinase (TK gene and a double mutant lacking TK and the glycoprotein E gene are fully attenuated for rabbits

    Directory of Open Access Journals (Sweden)

    S.C. Silva

    2010-02-01

    Full Text Available Bovine herpesvirus 5 (BoHV-5, the agent of herpetic meningoencephalitis in cattle, is an important pathogen of cattle in South America and several efforts have been made to produce safer and more effective vaccines. In the present study, we investigated in rabbits the virulence of three recombinant viruses constructed from a neurovirulent Brazilian BoHV-5 strain (SV507/99. The recombinants are defective in glycoprotein E (BoHV-5gEΔ, thymidine kinase (BoHV-5TKΔ and both proteins (BoHV-5gEΔTKΔ. Rabbits inoculated with the parental virus (N = 8 developed neurological disease and died or were euthanized in extremis between days 7 and 13 post-infection (pi. Infectivity was detected in several areas of their brains. Three of 8 rabbits inoculated with the recombinant BoHV-5gEΔ developed neurological signs between days 10 and 15 pi and were also euthanized. A more restricted virus distribution was detected in the brain of these animals. Rabbits inoculated with the recombinants BoHV-5TKΔ (N = 8 or BoHV-5gEΔTKΔ (N = 8 remained healthy throughout the experiment in spite of variable levels of virus replication in the nose. Dexamethasone (Dx administration to rabbits inoculated with the three recombinants at day 42 pi did not result in viral reactivation, as demonstrated by absence of virus shedding and/or increase in virus neutralizing titers. Nevertheless, viral DNA was detected in the trigeminal ganglia or olfactory bulbs of all animals at day 28 post-Dx, demonstrating they were latently infected. These results show that recombinants BoHV-5TKΔ and BoHV-5gEΔTKΔ are attenuated for rabbits and constitute potential vaccine candidates upon the confirmation of this phenotype in cattle.

  10. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen Libo, E-mail: libochen888@hotmail.com [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Guo Guoying [Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Liu Tianjing; Guo Lihe [Division of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2011-07-15

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated {sup 125}I{sup -} up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T{sub 1/2eff} of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or {sup 131}I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%{+-}2.5%, 43.4%{+-}2.8% and 8.6%{+-}1.2% after exposure to {sup 131}I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  11. Role of Genotypic Analysis of the Thymidine Kinase Gene of Herpes Simplex Virus for Determination of Neurovirulence and Resistance to Acyclovir

    Science.gov (United States)

    Lee, N. Y.; Tang, Y.-W.; Espy, M. J.; Kolbert, C. P.; Rys, P. N.; Mitchell, P. S.; Day, S. P.; Henry, S. L.; Persing, D. H.; Smith, T. F.

    1999-01-01

    Mutations in the thymidine kinase (TK) gene of herpes simplex virus (HSV) have been associated with resistance to acyclovir (ACY) and possible recognition of neurotropic strains. We sequenced a 335-bp segment of the TK gene to determine the frequency of mutations in HSV strains recovered from dermal, genital, and cerebrospinal fluid (CSF) specimens (n = 200; 102 HSV type 1 [HSV-1] 98 HSV-2 strains). Four polymorphic sites were detected in HSV-1 strains; C513T, A528G, C575T, and C672T. Among the polymorphisms, only C575T resulted in a change of amino acid sequence (residue 192, Ala→Val). For HSV-2 strains, only one polymorphism (G420T) which resulted in an amino acid substitution (residue 139, Leu→Phe) was detected. Phenotypic determination of resistance to ACY by a plaque reduction assay of 48 HSV isolates was not correlated with the sequence results of 11 strains in that 7 of these with genotypic polymorphisms were susceptible to the drug in vitro. In addition, of 32 ACY-resistant HSV strains, 28 (87.5%) had no polymorphisms detected in the 335-bp amplicon of the TK gene. There was no statistical difference in the frequency of polymorphisms according to the source of the specimens. We conclude that the detection of nucleic acid polymorphisms in a previously implicated 335-bp segment of the TK gene cannot be interpreted as indicative of either ACY resistance or neurotropism of HSV strains from dermal, genital, and CSF sources. PMID:10488172

  12. 5-[{sup 18}F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Chacko, Ann-Marie [Institute for Environmental Medicine, Targeted Therapeutics Program, University of Pennsylvania, Philadelphia, PA 19104 (United States); Blankemeyer, Eric; Lieberman, Brian P.; Qu, Wenchao [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)], E-mail: kunghf@gmail.com

    2009-01-15

    Introduction: The preliminary in vivo evaluation of novel 5-[{sup 18}F]fluoroalkyl-2'-deoxyuridines ([{sup 18}F]FPrDU, [{sup 18}F]FBuDU, [{sup 18}F]FPeDU; [{sup 18}F]1a-c, respectively) and 2'-fluoro-2'-deoxy-5-[{sup 18}F]fluoroalkyl-1-{beta}-D-arabinofuranosyl uracils ([{sup 18}F]FFPrAU, [{sup 18}F]FFBuAU, [{sup 18}F]FFPeAU; [{sup 18}F]1d-f, respectively) as probes for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is described. Methods: [{sup 18}F]1a-f were successfully synthesized by a rapid and efficient two-step one-pot nucleophilic fluorination reaction using 5-O-mesylate precursors and [{sup 18}F]F{sup -}. For in vivo studies, tumor xenografts were grown in nude mice by implanting RG2 cells stably expressing HSV1-tk (RG2TK+) and wild-type cells (RG2). Results: Biodistribution studies at 2 h pi revealed that the uptake of [{sup 18}F]1a-b and [{sup 18}F]1d-e in RG2TK+ tumors was not significantly different from control tumors. However, [{sup 18}F]1c and [{sup 18}F]1f had an average 1.6- and 1.7-fold higher uptake in RG2TK+ tumors than control RG2 tumors. Blood activity curves for [{sup 18}F]1c and [{sup 18}F]1f highlight rapid clearance of radioactivity in the blood. Dynamic small animal PET (A-PET) imaging studies of tumor-bearing mice with [{sup 18}F]1c and [{sup 18}F]1f showed higher initial uptake (3.5- and 1.4-fold, respectively) in RG2TK+ tumors than in control tumors, with continued washout of activity from both tumors over time. Conclusions: Biological evaluations suggest that [{sup 18}F]1c and [{sup 18}F]1f may have limited potential for imaging HSV1-tk gene expression due to fast washout of activity from the blood, thus significantly decreasing sensitivity and specificity of tracer accumulation in HSV1-tk-expressing tumors.

  13. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production.

    Science.gov (United States)

    Meng, Qiao; Hagemeier, Stacy R; Fingeroth, Joyce D; Gershburg, Edward; Pagano, Joseph S; Kenney, Shannon C

    2010-05-01

    Ganciclovir (GCV) and acyclovir (ACV) are guanine nucleoside analogues that inhibit lytic herpesvirus replication. GCV and ACV must be monophosphorylated by virally encoded enzymes to be converted into nucleotides and incorporated into viral DNA. However, whether GCV and/or ACV phosphorylation in Epstein-Barr virus (EBV)-infected cells is mediated primarily by the EBV-encoded protein kinase (EBV-PK), the EBV-encoded thymidine kinase (EBV-TK), or both is controversial. To examine this question, we constructed EBV mutants containing stop codons in either the EBV-PK or EBV-TK open reading frame and selected for stable 293T clones latently infected with wild-type EBV or each of the mutant viruses. Cells were induced to the lytic form of viral replication with a BZLF1 expression vector in the presence and absence of various doses of GCV and ACV, and infectious viral titers were determined by a green Raji cell assay. As expected, virus production in wild-type EBV-infected 293T cells was inhibited by both GCV (50% inhibitory concentration [IC(50)] = 1.5 microM) and ACV (IC(50) = 4.1 microM). However, the EBV-PK mutant (which replicates as well as the wild-type (WT) virus in 293T cells) was resistant to both GCV (IC(50) = 19.6 microM) and ACV (IC(50) = 36.4 microM). Expression of the EBV-PK protein in trans restored GCV and ACV sensitivity in cells infected with the PK mutant virus. In contrast, in 293T cells infected with the TK mutant virus, viral replication remained sensitive to both GCV (IC(50) = 1.2 microM) and ACV (IC(50) = 2.8 microM), although susceptibility to the thymine nucleoside analogue, bromodeoxyuridine, was reduced. Thus, EBV-PK but not EBV-TK mediates ACV and GCV susceptibilities.

  14. Evaluation of a C57BL/6J × 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis.

    Science.gov (United States)

    Hamilton, G F; Majdak, P; Miller, D S; Bucko, P J; Merritt, J R; Krebs, C P; Rhodes, J S

    2015-01-01

    New neurons are continuously generated in the adult hippocampus but their function remains a mystery. The nestin thymidine kinase (nestin-TK) transgenic method has been used for selective and conditional reduction of neurogenesis for the purpose of testing the functional significance of new neurons in learning, memory and motor performance. Here we explored the nestin-TK model on a hybrid genetic background (to increase heterozygosity, and "hybrid vigor"). Transgenic C57BL/6J (B6) were crossed with 129S1/SvImJ (129) producing hybrid offspring (F1) with the B6 half of the genome carrying a herpes simplex virus thymidine kinase (TK) transgene regulated by a modified nestin promoter. In the presence of exogenously administered valganciclovir, new neurons expressing TK undergo apoptosis. Female B6 nestin-TK mice ( n = 80) were evaluated for neurogenesis reduction as a positive control. Male and female F1 nestin-TK mice ( n = 223) were used to determine the impact of neurogenesis reduction on the Morris water maze (MWM) and rotarod. All mice received BrdU injections to label dividing cells and either valganciclovir or control chow, with or without a running wheel for 30 days. Both the F1 and B6 background displayed approximately 50% reduction in neurogenesis, a difference that did not impair learning and memory on the MWM or rotarod performance. Running enhanced neurogenesis and performance on the rotarod but not MWM suggesting the F1 background may not be suitable for studying pro-cognitive effects of exercise on MWM. Greater reduction of neurogenesis may be required to observe behavioral impacts. Alternatively, new neurons may not play a critical role in learning, or compensatory mechanisms in pre-existing neurons could have masked the deficits. Further work using these and other models for selectively reducing neurogenesis are needed to establish the functional significance of adult hippocampal neurogenesis in behavior.

  15. The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position

    International Nuclear Information System (INIS)

    Byun, Youngjoo; Yan Junhua; Al-Madhoun, A.S.; Johnsamuel, Jayaseharan; Yang Weilian; Barth, R.F.; Eriksson, Staffan; Tjarks, Werner

    2004-01-01

    Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase 1 in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues

  16. Long-term observation of herpes simplex virus type 1 (HSV-1) infection in a child with Wiskott-Aldrich syndrome and a possible reactivation mechanism for thymidine kinase-negative HSV-1 in humans.

    Science.gov (United States)

    Shiota, Tomoyuki; Kurane, Ichiro; Morikawa, Shigeru; Saijo, Masayuki

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) infections in a child with congenital immunodeficiency syndrome were observed over a 10-year period. The child suffered from recurrent and severe HSV-1 mucocutaneous infections. He frequently suffered from acyclovir (ACV)-resistant (ACV(r)) HSV-1 infection in the later phase of his life, especially after the episode of ACV(r) HSV-1 infection. Virological analyses on the HSV-1 isolates recovered from this patient revealed that all the ACV(r) HSV-1 isolates were thymidine kinase (TK)-negative (TK(-)) due to a single cytosine (C) deletion within the 4-C residues (positions 1061 to 1064) in the TK gene, indicating that the recurrent TK(-)/ACV(r) HSV-1 infections throughout the patient's life were due to the identical ACV(r) HSV-1 strain. Furthermore, it was found that the ACV-sensitive (ACV(s)) isolate recovered from the skin lesions that appeared between the episodes of ACV(r) infection at the ages of 8 and 9 contained ACV(r) HSV-1 with the same mutation in the TK gene. These results indicate that, although TK activity is required for reactivation of TK(+)/ACV(s) HSV-1 from latency and TK(-)/ACV(r) HSV-1 is unable to reactivate from latency, the TK(-)/ACV(r) HSV-1 strain isolated herein reactivated in this patient, possibly by using the TK activity induced by the latently co-infected TK(+)/ACV(s) HSV-1.

  17. Evaluation of F-18-labeled 5-iodocytidine ({sup 18}F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Pei-Chia; Wu, Chun-Yi; Chang, Wen-Yi; Chang, Wei-Ting [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Alauddin, Mian [Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, TX, 77054 (United States); Liu, Ren-Shan [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Lin, Wuu-Jyh [Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 32546, Taiwan (China); Chen, Fu-Du [College of Health and Leisure Science, TransWorld University, Yunlin, 64063, Taiwan (China); Chen, Chuan-Lin, E-mail: clchen2@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Wang, Hsin-Ell, E-mail: hewang@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China)

    2011-10-15

    Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[{sup 18}F]fluoro-{beta}-D-arabinofuranosyl)-5-iodocytosine ({sup 18}F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ({sup 18}F-FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil({sup 18}F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6{+-}25.1, 76.3{+-}18.2 and 247.2{+-}37.2, respectively. In biodistribution studies, {sup 18}F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with {sup 18}F-FIAU (15.8) but lower than {sup 18}F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue {sup 18}F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. {sup 18}F-FIAC may be regarded as the prodrug of {sup 18}F-FIAU in vivo.

  18. Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression with Radiolabeled 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in Liver by Hydrodynamic-based Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Song, In Ho; Lee, Tae Sup; Kang, Joo Hyun; Lee, Yong Jin; Kim, Kwang Il; An, Gwang Il; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-10-15

    Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynamic injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.

  19. In Vitro and In Vivo Characterization of a Dual-Function Green Fluorescent Protein–HSV1-Thymidine Kinase Reporter Gene Driven by the Human Elongation Factor 1α Promoter

    Directory of Open Access Journals (Sweden)

    Gary D. Luker

    2002-04-01

    Full Text Available Toward the goal of monitoring activity of native mammalian promoters with molecular imaging techniques, we stably transfected DU145 prostate carcinoma cells with a fusion construct of enhanced green fluorescent protein (EGFP and wild-type herpes simplex virus-1 thymidine kinase (HSV1-TK as a reporter gene driven by the promoter for human elongation factor 1α (EF-1α-EGFP-TK. Using this model system, expression of EGFP was quantified by flow cytometry and fluorescence microscopy, while the HSV1-TK component of the reporter was quantified with 8-[3H]ganciclovir (8-[3H]GCV. As analyzed by flow cytometry, passage of EGFP-TK-DU145 transfected cells (ETK in vitro resulted in populations of cells with high and low expression of EGFP over time. High and low ETK cells retained 23-fold and 5-fold more GCV, respectively, than control. While differences in uptake and retention of GCV corresponded to relative expression of the reporter gene in each subpopulation of cells as determined by both flow cytometry (EGFP and quantitative RT-PCR, the correlation was not linear. Furthermore, in high ETK cells, net retention of various radiolabeled nucleoside analogues varied; the rank order was 8-[3H]GCV < 9-(4-fluoro-3-hydroxymethylbutylguanine ([18F]FHBG ≈ 8-[3H]penciclovir (8-[3H]PCV < 2′-fluoro-2′-deoxy-5-iodouracil-beta-d-arabinofuranoside (2-[14C]FIAU. Xenograft tumors of ETK cells in vivo accumulated 2.5-fold more 8-[3H]GCV per gram of tissue and showed greater fluorescence from EGFP than control DU145 cells, demonstrating that the reporter gene functioned in vivo. These data extend previous reports by showing that a human promoter can be detected in vitro and in vivo with a dual-function reporter exploiting optical and radiotracer techniques.

  20. Suicide

    Science.gov (United States)

    Suicide is the tenth most common cause of death in the United States. People may consider suicide when they are hopeless and can't see ... event. People who have the highest risk of suicide are white men. But women and teens report ...

  1. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vernis, L.; Piskur, Jure; Diffley, J.F.X.

    2003-01-01

    The budding yeast Saccharomyces cerevisiae is unable to incorporate exogenous nucleosides into DNA. We have made a number of improvements to existing strategies to reconstitute an efficient thymidine salvage pathway in yeast. We have constructed strains that express both a nucleoside kinase as well...

  2. Validation of ( sup 3 H)thymidine incorporation and its application to detecting natural transformation in the marine environment

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey, W.H.

    1989-01-01

    The ({sup 3}H)thymidine incorporation method to estimate bacterial DNA synthesis and heterotrophic production was examined by investigating the four major factors and assumptions associated with the technique. When compared to fluorometrically determined rates of DNA synthesis, ({sup 3}H)thymidine incorporation consistently underestimated DNA synthesis by 6 to 8-fold, indicating the inability of ({sup 3}H)thymidine incorporation and isotope dilution assays to accurately determine the amount of thymine bases incorporated into DNA. Non-specific labeling of macromolecules other than DNA was ubiquitous and the percentage of radioactivity incorporated into DNA was inversely related to total rates thymidine incorporation but independent of any other parameter examined. The use of specific inhibitors and a comparison of (methyl-{sup 3}H)thymidine with (6-{sup 3}H)thymidine indicated that non-specific labelling was not the result of a demethylation reaction but the result of ({sup 3}H)thymine catabolism. Four of the 41 marine bacterial isolates examined were incapable of incorporating thymidine into DNA and lacked thymidine transport and thymidine kinase activity. Transformation of an E. coli tdk into one of these organisms resulted in high levels of thymidine kinase activity but no capacity to incorporate or transport thymidine by this organism.

  3. Suppression of phytohemagglutinin-induction of thymidine uptake in guinea pig lymphocytes by methylglyoxal bis(guanylhydrazone) treatment.

    Science.gov (United States)

    Otani, S; Matsui, I; Morisawa, S

    1977-10-18

    Treatment with methylglyoxal bis(guanylhydrazone), a specific inhibitor of S-adenosylmethionine decarboxylase (EC 4.1.1.50), suppressed the phytohemagglutinin-induction of [3H]thymidine uptake by guinea pig lymphocytes. The kinetics of [3H]thymidine uptake revealed that the Km value for thymidine was not changed, but the V value was markedly lowered by the methylglyoxal bis(guanylhydrazone) treatment. The induction of ATP: thymidine 5'-phosphotransferase (EC 2.7.1.75) (thymidine kinase) activity by phytohemagglutinin was suppressed to about the same extent as the induction of thymidine uptake. These suppressions were dependent on the methylglyoxal bis(guanylhydrazone) doses and on duration of the methylglyoxal bis(guanylhydrazone) treatment. Analysis of [3H]thymidine labelled compounds of the acid-soluble fraction showed that conversion of thymidine to thymidine 5'-triphosphate was inhibited by the methylglyoxal bis(guanylhydrazone) treatment. DNA polymerase activity was less inhibited by the methylglyoxal bis(guanylhydrazone) treatment in comparison with the methylglyoxal bis(guanylhydrazone) inhibition of thymidine uptake by whole cells. These results strongly suggested that blocking of polyamine accumulation by the methylglyoxal bis(guanylhydrazone) treatment influenced phytohemagglutinin induction of thymidine phosphorylation, resulting in a decrease of thymidine incorporation into DNA.

  4. Thymidine secretion by hybridoma and myeloma cells

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Rise, Frode; Petersen, Dirk; Nissen-Meyer, Jon

    2006-01-01

    Secretion of thymidine appeared to be a common property of hybridoma and myeloma cells, but not of other cell types, which were tested. Of three hybridoma cell lines tested, all secreted thymidine in amounts resulting in the accumulation of thymidine to concentrations of 10-20 μM in the culture medium. Also three of five myeloma cell lines that were analyzed secrete thymidine, but none of the other cell types that were studied. Thymidine was purified to homogeneity (4 mg purified from 3 l of culture medium) and identified as such by nuclear magnetic resonance spectroscopy. The cells that secreted thymidine showed high resistance to the growth inhibitory effect of thymidine

  5. Suicide

    Science.gov (United States)

    ... impossible. In a military setting, the impact effects morale, unit cohesion, and ultimately unit effectiveness. 2.1 ... are considered to be personal protective factors:  Attitudes, values, and norms prohibiting suicide, for example strong beliefs ...

  6. Suicide

    DEFF Research Database (Denmark)

    Bjerregaard, Peter; Lynge, Inge

    2006-01-01

    in the capital, a later peak in the rest of West Greenland, and high and increasing rates in remote East Greenland. Suicidal thoughts occur more often in young people who grew up in homes with a poor emotional environment, alcohol problems and violence. There is a definite correlation with several aspects...

  7. Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

    NARCIS (Netherlands)

    Bijnsdorp, I. V.; Azijli, K.; Jansen, E. E.; Wamelink, M. M.; Jakobs, C.; Struys, E. A.; Fukushima, M.; Kruyt, F. A. E.; Peters, G. J.

    2010-01-01

    Thymidine phosphorylase (TP) is often overexpressed in cancer and potentially plays a role in the stimulation of angiogenesis The exact mechanism of angiogenesis induction is unclear, but is postulated to be related to thymidine-derived sugars. TP catalyzes the conversion of thymidine (TdR) to

  8. Radiosensitization of thymidine in deaerated aqueous solution

    International Nuclear Information System (INIS)

    Berger, Maurice.

    1982-09-01

    This work investigates the mode of action of various radiosensitizing agents on the radio-induced degradation of thymidine in deaerated aqueous solution. A special effort was devoted to the separation of addition products formed by one of these substances (a stable nitroxide radical: TAN) with the radio-induced neutral radicals of thymidine. The complex mixture of different diastereoisomers resulting from the covalent addition of the TAN molecule on the thymidine carbons C (5) or C (6) was resolved by HPLC. The structural determination of these adducts (absolute configuration) was achieved by various spectroscopic techniques and specific chemical syntheses. A conformational study has been undertaken [fr

  9. The engineered thymidylate kinase (TMPK/AZT enzyme-prodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer.

    Directory of Open Access Journals (Sweden)

    Takeya Sato

    Full Text Available We previously described a novel suicide (or 'cell fate control' gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK that potentiates azidothymidine (AZT activation. Delivery of a suicide gene sequence into tumors by lentiviral transduction embodies a cancer gene therapy that could employ bystander cell killing as a mechanism driving significant tumor regression in vivo. Here we present evidence of a significant bystander cell killing in vitro and in vivo mediated by the TMPK/AZT suicide gene axis that is reliant on the formation of functional gap-junctional intercellular communications (GJICs. Potentiation of AZT activation by the engineered TMPK expressed in the human prostate cancer cell line, PC-3, resulted in effective bystander killing of PC-3 cells lacking TMPK expression--an effect that could be blocked by the GJIC inhibitor, carbenoxolone. Although GJICs are mainly formed by connexins, a new family of GJIC molecules designated pannexins has been recently identified. PC-3 cells expressed both connexin43 (Cx43 and Pannexin1 (Panx1, but Panx1 expression predominated at the plasma membrane, whereas Cx43 expression was primarily localized to the cytosol. The contribution of bystander effects to the reduction of solid tumor xenografts established by the PC-3 cell line was evaluated in an animal model. We demonstrate the contribution of bystander cell killing to tumor regression in a xenograft model relying on the delivery of expression of the TMPK suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. Taken together, our data underscore that the TMPK/AZT enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors, wherein significant tumor regression can be achieved via bystander effects mediated by GJICs.

  10. The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells

    International Nuclear Information System (INIS)

    Franzolin, Elisa; Miazzi, Cristina; Frangini, Miriam; Palumbo, Elisa; Rampazzo, Chiara; Bianchi, Vera

    2012-01-01

    In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [ 3 H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1 − cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1 + cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. -- Highlights: ► Thymidine phosphates exchange between mitochondria and cytosol in mammalian cells. ► siRNA-downregulation of PNC1 delays mitochondrial dTTP export in TK1 − cells. ► PNC1 overexpression accumulates dTTP in mitochondria of TK1 + cells. ► PNC1 exchanges thymidine nucleotides across the mitochondrial inner membrane. ► PNC1 participates in the regulation of the mtdTTP pool supporting mtDNA synthesis.

  11. Improving the Safety of Cell Therapy Products by Suicide Gene Transfer

    Directory of Open Access Journals (Sweden)

    Antonio eDi Stasi

    2014-11-01

    Full Text Available Adoptive T-cell therapy can involve donor lymphocyte infusion (DLI after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte (TILs expanded ex-vivo, or more recently the use of T cell receptor (TCR or chimeric antigen receptor (CAR redirected T cells. However cellular therapies can pose significant risks, including graft-versus-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The ‘ideal’ suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of ‘all’ and ‘only’ the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase (HSV-TK and inducible-caspase-9 (iCasp9.

  12. Improving the safety of cell therapy products by suicide gene transfer.

    Science.gov (United States)

    Jones, Benjamin S; Lamb, Lawrence S; Goldman, Frederick; Di Stasi, Antonio

    2014-01-01

    Adoptive T-cell therapy can involve donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte expanded ex-vivo, or more recently the use of T cell receptor or chimeric antigen receptor redirected T cells. However, cellular therapies can pose significant risks, including graft-vs.-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The "ideal" suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of "all" and "only" the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase and inducible-caspase-9.

  13. Thymidine kinase 1 regulatory fine-tuning through tetramer formation

    DEFF Research Database (Denmark)

    Mutahir, Zeeshan; Clausen, Anders R.; Andersson, Karl-Magnus

    2013-01-01

    concentration-dependent transition of TK1 from a dimer with low catalytic efficiency to a tetramer with high catalytic efficiency. This regulatory fine-tuning serves as an additional control to provide a balanced pool of nucleic acid precursors in the cell. We subcloned and over-expressed 10 different TK1s...

  14. Structures of thymidine kinase 1 of human and mycoplasma origin

    DEFF Research Database (Denmark)

    Welin, Martin; Kosinska, Urszula; Mikkelsen, Nils-Egil

    2004-01-01

    , in complex with the feedback inhibitor dTTP. The TK1s have a tetrameric structure where each subunit contains an alfa/beta-domain that is similar to ATPase domains of members of the RecA structural family and a domain of a new type containing a structural zinc. The zinc ion connects beta...

  15. Determination of thymidine in serum used for cell culture media

    International Nuclear Information System (INIS)

    Schaer, J.C.; Maurer, U.; Schindler, R.

    1978-01-01

    Thymidine concentrations in serum used for cell culture media were determined with an assay based on isotope dilution. In this assay, incorporation of (3H)-thymidine into DNA of cultured cells was measured in the presence of 5 and 20% serum as a function of the concentration of unlabeled thymidine added to the medium. Thymidine concentrations were measured using horse serum as well as fetal calf serum in the culture media. Dialysis of serum resulted in a reduction of thymidine levels by factors of at least 10

  16. Molecular moment similarity between several nucleoside analogs of thymidine and thymidine. sil@watson.ibm.com.

    Science.gov (United States)

    Silverman, B D; Pitman, M C; Platt, D E

    1999-06-01

    Molecular moment descriptors of the shape and charge distributions of twenty five nucleoside structures have been examined. The structures include thymidine as well as the difluorotoluene nucleoside analog which has been found to pair efficiently with adenine by polymerase catalysis. The remaining twenty three structures have been chosen to be as structurally similar to thymidine and to the difluorotoluene nucleoside analog as possible. The moment descriptors which include a description of the relationship of molecular charge to shape show the difluorotoluene nucleoside to be one of the most proximate molecules to thymidine in the space of the molecular moments. The calculations, therefore, suggest that polymerase specificity might be not only a consequence of molecular steric features alone but also of the molecular electrostatic environment and its registration with molecular shape.

  17. Photoreaction of 8-methoxypsoralen with thymidine

    International Nuclear Information System (INIS)

    Shim, S.C.; Kim, Y.Z.

    1983-01-01

    The photoreaction of 8-methoxypsoralen (8-MOP) with thymidine in solid film state yielded two 4',5'-monoadducts (a pair of diastereomers) and three 3,4-monoadducts. The stereochemistry of two 4',5'monoadducts was found to be cis-syn and trans-syn and one 3,4-monoadduct was cis-anti. In addition to these monoadducts, 3,4-, 4',5-biadducts were also formed during the reaction, but the isolation of each isomer of these adducts was not successful; however, the formation of these biadducts was confirmed by UV, IR, TLC and photosplitting experiments. (author)

  18. Suicide and Suicidal Thoughts

    Science.gov (United States)

    ... with an unsupportive family or in a hostile environment Attempted suicide before Children and teenagers Suicide in children and teenagers often ... 10, 2015. Kennebeck S, et al. Suicidal behavior in children and ... murder-suicide. American Journal of Men's Health. In press. Accessed April 10, ...

  19. Effects of an adenoviral vector containing a suicide gene fusion on growth characteristics of breast cancer cells.

    Science.gov (United States)

    Kong, Heng; Liu, Chunli; Zhu, Ting; Huang, Zonghai; Yang, Liucheng; Li, Qiang

    2014-12-01

    The herpes simplex virus thymidine kinase/ganciclovir (HSV‑TK/GCV) and the cytosine deaminase/5‑fluorocytosine (CD/5‑FC) systems have been widely applied in suicide gene therapy for cancer. Although suicide gene therapy has been successfully used in vitro and in vivo studies, the number of studies on the effects of recombinant adenoviruses (Ads) containing suicide genes on target cancer cells is limited. The aim of this study was to examine whether recombinant Ads containing the CD/TK fusion gene affect cell proliferation of breast cancer cells in vitro. In the present study, we explored the use of a recombinant adenoviral vector to deliver the CD/TK fusion gene to the breast cancer cell line MCF‑7. We found that the recombinant adenoviral vector efficiently infected MCF‑7 cells. Western blot analysis revealed that CD and TK proteins are expressed in the infected cells. The infected breast cancer cells did not show any significant changes in morphology, ultrastructure, cell growth, and cell‑cycle distribution compared to the uninfected cells. This study revealed that the Ad‑vascular endothelial growth factor promoter (VEGFp)‑CD/TK vector is non‑toxic to MCF‑7 cells at the appropriate titer. Our results indicate that it is feasible to use a recombinant adenoviral vector containing the CD/TK fusion gene in suicide gene therapy to target breast cancer cells.

  20. X chromosome and suicide.

    Science.gov (United States)

    Fiori, L M; Zouk, H; Himmelman, C; Turecki, G

    2011-02-01

    Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90  kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

  1. Suicide and suicidal behavior

    Science.gov (United States)

    ... more likely to choose violent methods, such as shooting themselves. As a result, suicide attempts by men ... wanting to go out Suddenly having trouble in school or work Talking about death or suicide, or ...

  2. Suicide and Suicidal Thoughts

    Science.gov (United States)

    ... a minister, spiritual leader or someone in your faith community Call a suicide hotline Make an appointment with your doctor, other health care provider or mental health provider Suicidal thinking ...

  3. Suicide and Suicidal Behavior

    Science.gov (United States)

    Nock, Matthew K.; Borges, Guilherme; Bromet, Evelyn J.; Cha, Christine B.; Kessler, Ronald C.; Lee, Sing

    2008-01-01

    Suicidal behavior is a leading cause of injury and death worldwide. Information about the epidemiology of such behavior is important for policy-making and prevention. The authors reviewed government data on suicide and suicidal behavior and conducted a systematic review of studies on the epidemiology of suicide published from 1997 to 2007. The authors' aims were to examine the prevalence of, trends in, and risk and protective factors for suicidal behavior in the United States and cross-nationally. The data revealed significant cross-national variability in the prevalence of suicidal behavior but consistency in age of onset, transition probabilities, and key risk factors. Suicide is more prevalent among men, whereas nonfatal suicidal behaviors are more prevalent among women and persons who are young, are unmarried, or have a psychiatric disorder. Despite an increase in the treatment of suicidal persons over the past decade, incidence rates of suicidal behavior have remained largely unchanged. Most epidemiologic research on suicidal behavior has focused on patterns and correlates of prevalence. The next generation of studies must examine synergistic effects among modifiable risk and protective factors. New studies must incorporate recent advances in survey methods and clinical assessment. Results should be used in ongoing efforts to decrease the significant loss of life caused by suicidal behavior. PMID:18653727

  4. Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans.

    OpenAIRE

    Pochet , Sylvie; Dugué , Laurence; Labesse , Gilles; Delepierre , Muriel; Munier-Lehmann , Hélène

    2003-01-01

    Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X-ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5-modified thymidine derivatives, as well as purine and pyrimidine analogues or C-nucleosides were tested on TMPKmt and TMPKh, and th...

  5. Reaction of Thymidine with Hypobromous Acid in Phosphate Buffer.

    Science.gov (United States)

    Suzuki, Toshinori; Kitabatake, Akihiko; Koide, Yuki

    2016-01-01

    When thymidine was treated with hypobromous acid (HOBr) in 100 mM phosphate buffer at pH 7.2, two major product peaks appeared in the HPLC chromatogram. The products in each peak were identified by NMR and MS as two isomers of 5-hydroxy-5,6-dihydrothymidine-6-phosphate (a novel compound) and two isomers of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol) with comparable yields. 5-Hydroxy-5,6-dihydrothymidine-6-phosphate was relatively stable, and decomposed with a half-life of 32 h at pH 7.2 and 37°C generating thymidine glycol. The results suggest that 5-hydroxy-5,6-dihydrothymidine-6-phosphate in addition to thymidine glycol may have importance for mutagenesis by the reaction of HOBr with thymine residues in nucleotides and DNA.

  6. Synthesis of 3'-O2-(azaheterocycle)-thymidines.

    Science.gov (United States)

    Prestat, G; Dubreuil, D; Adjou, A; Pradère, J P; Lebreton, J; Evers, M; Henin, Y

    2000-04-01

    The synthesis of 3'-O2-(azaheterocycle)-thymidines is presented from 1-thia-3-aza- 1,3-butadiene precursors (N-thioacylamidines). A variety of heterocycles is accessible using the dienic, the electrophilic or the nucleophilic reactivity of these thia-azabutadiene systems. 3'-O2-(azaheterocycle)-thymidine analogues are regarded as potential substrates to interfere with the DNA-polymerization process.

  7. Suicide notes.

    Science.gov (United States)

    O'Donnell, I; Farmer, R; Catalan, J

    1993-07-01

    Detailed case reports of incidents of suicide and attempted suicide on the London Underground railway system between 1985 and 1989 were examined for the presence of suicide notes. The incidence of note-leaving was 15%. Notes provided little insight into the causes of suicide as subjectively perceived, or strategies for suicide prevention.

  8. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Rim Hojeij

    2016-07-01

    Full Text Available Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC and it is amenable to local treatments, with intravesical (IVES Bacillus-Calmette-Guerin (BCG immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK combined to Ganciclovir (GCV led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

  9. Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

    Directory of Open Access Journals (Sweden)

    Jianqing Pan

    Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

  10. Elderly Suicide

    Science.gov (United States)

    Elderly Suicide Fact Sheet Based on 2012 Data (2014) Overview • The elderly (ages 65 and older) made up 13. ... population; they accounted for 16.37% of all suicides in the US. • The rate of suicides for ...

  11. Synthesis of tritiated thymine and thymidine with high specific activity

    International Nuclear Information System (INIS)

    Shimoni, M.; Buchman, O.

    1977-05-01

    The synthesis of the following compounds is described: (a) thymine - 6 -3 H, with a specific activity of 17.5 Ci/mmol, obtained by the following steps: preparation of uracil - 6 -3 H; chloroformylation of uracil - 6 -3 H; de-halogenation of chloromethyl thymine - 6 -3 H. (b) thymine - methyl -3 H, with a specific activity of 31 Ci/mmol, obtained by reduction of 5 - formyluracil with tritium. (c) thymidine - 6 -3 H and thymidine - methyl -3 H, with specific activities of 8 Ci/mmol and 25 Ci/mmol, respectively, obtained by enzymatic reaction

  12. Adolescent Suicide and Suicidal Behavior

    Science.gov (United States)

    Bridge, Jeffrey A.; Goldstein, Tina R.; Brent, David A.

    2006-01-01

    This review examines the descriptive epidemiology, and risk and protective factors for youth suicide and suicidal behavior. A model of youth suicidal behavior is articulated, whereby suicidal behavior ensues as a result of an interaction of socio-cultural, developmental, psychiatric, psychological, and family-environmental factors. On the basis of…

  13. Deoxyribonucleoside triphosphate pools and thymidine chemosensitization in human T-cell leukemia.

    Science.gov (United States)

    Cohen, J D; Robins, H I; Katz, T B; Miller, E M; Kuzminsky, S R; Javid, M J

    1993-02-01

    Thymidine kills cells by depleting dCTP stores. The present experiments tested whether deoxycytidine, by replenishing dCTP pools, could prevent thymidine cytotoxicity and thymidine's enhancement of carboplatin killing in two human T-cell acute leukemia cell lines. MOLT3 and JM cells were exposed to combinations of thymidine, deoxycytidine, and carboplatin and then assessed for survival, the magnitude of thymidine-carboplatin chemosensitization, and changes in deoxyribonucleoside triphosphate pools. For both cell lines, deoxycytidine (up to 144.5 micrograms/ml x 24 h) completely restored dCTP pools but only partially protected against thymidine cytotoxicity (100-1000 micrograms/ml x 24 h) and thymidine-carboplatin sensitization (up to 60 micrograms carboplatin/ml during the last hour of thymidine). This contrasts with complete protection in prior studies using other cell types. Thymidine alone markedly increased dTTP and dGTP pools and decreased dCTP; dATP pools underwent a sharp decline which has not been observed before in any cell line. In subsequent studies 0.0336-137.3 micrograms deoxyadenosine/ml partially prevented cytotoxicity and carboplatin sensitization by 300 micrograms thymidine/ml. Together, deoxycytidine and deoxyadenosine completely prevented thymidine-carboplatin sensitization even though dATP and dCTP pools were not entirely returned to normal. These findings are discussed in regard to the unusual sensitivity of T-cell malignancies to thymidine toxicity, mechanisms of cytotoxicity and chemosensitization by thymidine, and the possibility of thymidine selectively sensitizing T-cell malignancies to killing by alkylating agents.

  14. Suicide Prevention

    Science.gov (United States)

    ... remember the good times and develop a more positive outlook. ( Back to top. ) If You Are Feeling Suicidal If you have begun to think of suicide, it's important to recognize these thoughts for what they are: expressions of a treatable, ...

  15. Suicide Prevention

    Science.gov (United States)

    ... Adults Podcast Series Q&A Peer Inspiration Life Unlimited Stories Life Unlimited Awards DBSA Honorary Advisory Board I'm Living ... suicide. As depression begins to lift, a person's energy and planning capabilities may return before the suicidal ...

  16. Lithium and suicide prevention in bipolar disorder.

    Science.gov (United States)

    Benard, V; Vaiva, G; Masson, M; Geoffroy, P A

    2016-06-01

    Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations. We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt". As confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/β (GSK3α and β; proteins inhibited by Li) seem to

  17. Deoxyribonucleoside kinases: two enzyme families catalyze the same reaction

    DEFF Research Database (Denmark)

    Sandrini, Michael; Piskur, Jure

    2005-01-01

    Mammals have four deoxyribonucleoside kinases, the cytoplasmic (TK1) and mitochondrial (TK2) thymidine kinases, and the deoxycytidine (dCK) and deoxyguanosine (dGK) kinases, which salvage the precursors for nucleic acids synthesis. In addition to the native deoxyribonucleoside substrates, the kin......, the kinases can phosphorylate and thereby activate a variety of anti-cancer and antiviral prodrugs. Recently, the crystal structure of human TK1 has been solved and has revealed that enzymes with fundamentally different origins and folds catalyze similar, crucial cellular reactions....

  18. Double suicide genes selectively kill human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Liu Lunxu

    2011-02-01

    Full Text Available Abstract Background To construct a recombinant adenovirus containing CDglyTK double suicide genes and evaluate the killing effect of the double suicide genes driven by kinase domain insert containing receptor (KDR promoter on human umbilical vein endothelial cells. Methods Human KDR promoter, Escherichia coli (E. coli cytosine deaminase (CD gene and the herpes simplex virus-thymidine kinase (TK gene were cloned using polymerase chain reaction (PCR. Plasmid pKDR-CDglyTK was constructed with the KDR promoter and CDglyTK genes. A recombinant adenoviral plasmid AdKDR-CDglyTK was then constructed and transfected into 293 packaging cells to grow and harvest adenoviruses. KDR-expressing human umbilical vein endothelial cells (ECV304 and KDR-negative liver cancer cell line (HepG2 were infected with the recombinant adenoviruses at different multiplicity of infection (MOI. The infection rate was measured by green fluorescent protein (GFP expression. The infected cells were cultured in culture media containing different concentrations of prodrugs ganciclovir (GCV and/or 5-fluorocytosine (5-FC. The killing effects were measured using two different methods, i.e. annexin V-FITC staining and terminal transferase-mediated dUTP nick end-labeling (TUNEL staining. Results Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed and they infected ECV304 and HepG2 cells efficiently. The infection rate was dependent on MOI of recombinant adenoviruses. ECV304 cells infected with AdKDR-CDglyTK were highly sensitive to GCV and 5-FC. The cell survival rate was dependent on both the concentration of the prodrugs and the MOI of recombinant adenoviruses. In contrast, there were no killing effects in the HepG2 cells. The combination of two prodrugs was much more effective in killing ECV304 cells than GCV or 5-FC alone. The growth of transgenic ECV304 cells was suppressed in the presence of prodrugs. Conclusion AdKDR-CDglyTK/double prodrog system may be a useful

  19. Suicidal communication signifies suicidal intent in Chinese completed suicides.

    Science.gov (United States)

    Zhou, Xue Mei; Jia, Shu Hua

    2012-11-01

    Recognizing suicidal communication from the distressful catharsis in a high-risk group with suicidal tendencies is essential for suicide prevention. This study analyzes whether suicidal communication can indicate the severity of suicidal intent. Various types of suicidal communication are defined, and their clinical significance is further explored. A comprehensive analysis of the psychological autopsy data of 200 victims of completed suicide, including their general socio-demographic status, suicidal communication methods, previous suicide attempts, mental disorders, and psychosocial situation. Our results showed that 39.5% of all the subjects were suicidal communicators, 23.0% had previously attempted suicide, and 14.0% left suicide notes; 32.4% of 142 subjects free of physical disease suffered from mental disorders. Suicidal communication included verbal communication, behavioral communication, and suicidal notes. Younger people with a higher level of education were more inclined to communicate their suicidal intent by leaving a suicide note. Suicide notes, but not previous suicide attempts or psychosocial situation, were significantly correlated with suicidal intent. Suicidal communicators showed higher depression scores than non-communicators. Those who suffered from mood disorders with higher levels of both depression and suicidal intent were more likely to expose their intent through behavioral communication. The present study provides strong evidence that suicidal communication can indicate the severity of suicidal intent. Current findings help interpret high-risk, self-destructive behavior and consequently provide the theoretical basis for a feasible suicide prevention program.

  20. SUICIDE IN RURAL COMMUNITY

    OpenAIRE

    Hedge, R. S.

    1980-01-01

    SUMMARY 51 suicides in a rural community of Northern Karnataka were studied for incidence, age and sex distribution, methods adopted for suicides, and causes of suicides. Suicides in rural area did not show any difference from urban suicide pattern.

  1. Formation of volatile decomposition products by self-radiolysis of tritiated thymidine

    International Nuclear Information System (INIS)

    Shiba, Kazuhiro; Mori, Hirofumi

    1997-01-01

    In order to estimate the internal exposure dose in an experiment using tritiated thymidine, the rate of volatile 3 H-decomposition of several tritiated thymidine samples was measured. The decomposition rate of (methyl- 3 H)thymidine in water was over 80% in less than one year after initial analysis. (methyl- 3 H)thymidine was decomposed into volatile and non-volatile 3 H-decomposition products. The ratio of volatile 3 H-decomposition products increased with increasing the rate of the decomposition of (methyl- 3 H) thymidine. The volatile 3 H-decomposition products consisted of two components, of which the main component was tritiated water. Internal exposure dose caused by the inhalation of such volatile 3 H-decomposition products of (methyl- 3 H) thymidine was assumed to be several μSv. (author)

  2. Using miniature osmotic infusion pumps to maintain tritiated thymidine exposure to cells in culture

    International Nuclear Information System (INIS)

    Neely, J.E.; Hake, D.A.

    1982-01-01

    To provide a constant level of tracer doses of tritiated thymidine to cultured cells during continuous infusion, miniature osmotic infusion pumps were used to provide replacement thymidine. By determining the loss of isotope from the media during nonreplacement, the rate of constant infusion replacement to maintain thymidine levels was calculated. The replacement rates were similar for the three cell lines examined and allowed a standard osmotic pump infusion

  3. Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

    International Nuclear Information System (INIS)

    Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori; Onodera, Masafumi; Sato, Miki; Du, Wei; Sasahara, Yoji; Tanaka, Nobuyuki; Sugamura, Kazuo; Tsuchiya, Shigeru

    2006-01-01

    Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial

  4. Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

    Science.gov (United States)

    Zhao, Y; Lam, D H; Yang, J; Lin, J; Tham, C K; Ng, W H; Wang, S

    2012-02-01

    Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

  5. Nucleoside phosphonic acids in thymidine phosphorylase inhibition: Structure - activity relationship

    Czech Academy of Sciences Publication Activity Database

    Panova, Natalya; Kóšiová, Ivana; Petrová, Magdalena; Vaněk, Václav; Liboska, Radek; Kovačková, Soňa; Kočalka, Petr; Králíková, Šárka; Točík, Zdeněk; Páv, Ondřej; Pačes, Ondřej; Rejman, Dominik; Rosenberg, Ivan

    -, č. 52 (2008), s. 665-666 ISSN 0261-3166. [Joint Symposium of the International Roundtable on Nucleosides, Nucleotides and Nucleic Acids /18./ and the International Symposium on Nucleic Acid Chemistry /35./. Kyoto, 08.09.2008-12.09.2008] R&D Projects: GA MŠk(CZ) LC06061; GA MŠk(CZ) LC06077; GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : thymidine phosphorylase * inhibitors * phosphonic acids Subject RIV: CC - Organic Chemistry

  6. Determining the specific activity of thymidine phosphorylase in leukocytes of patients with MNGIE and the plasma thymidine level by RP-HPLC

    Directory of Open Access Journals (Sweden)

    Rezaei Sh

    2011-06-01

    Full Text Available "nBackground: Thymidine phosphorylase (TP catalyses the conversion of thymidine into thymine. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE is an autosomal recessive disease which is caused by mutations in the nuclear gene encoding TP, bringing about severe impairment of TP-enzyme specific activity and accumulation of thymidine in plasma. The clinical manifestations of MNGIE are recognizable and homogenous, but not in the early stages of the disease. In patients who are suspected of having MNGIE, determination of TP-specific activity in leukocytes and thymidine levels in plasma are diagnostic. The methods that are usually used for the measurement of TP activity and plasma thymidine are not rapid or accurate enough and lack sensitivity."n "nMethods: The specific activity of TP was measured by RP-HPLC in leukocytes of both the controls and the patients exhibiting clinical features suggestive of MNGIE. Moreover, plasma thymidine was assessed by the same method."n "nResults: The patients had detectable plasma thymidine (>3 µmol/L but it was undetectable in the healthy controls. The patients' TP-specific activity decreased to less than 5% relative to the controls (14±4 nmol/h/mg vs. 525±165 nmol/h/mg, P<0.05. A diagnostic algorithm for the definitive diagnosis of MNGIE is suggestible based on the results of this study which relies on the measurement of plasma thymidine, TP-specific activity in leukocytes, or both."n "nConclusion: In this study, we set up a sensitive and rapid assay for the evaluation of TP-specific activity by using RP-HPLC in Iran. In addition, we established reference values for TP-specific activity and plasma thymidine in the Iranian patients.

  7. Dual monitoring using 124I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    International Nuclear Information System (INIS)

    Lee, T. S.; Kim, J. H.; Kwon, H. C.

    2007-01-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[ 124 I] iodouracil ( 124 I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ( 124 I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, 124 I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, 124 I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by 124 I-FIAU PET imaging. 124 I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. 124 I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials

  8. Thymidine phosphorylase influences [{sup 18}F]fluorothymidine uptake in cancer cells and patients with non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin [Gachon University, College of Pharmacy, Incheon (Korea, Republic of); Yeo, Jeong Seok [Dongguk University Ilsan Hospital, Department of Nuclear Medicine, Goyang-si (Korea, Republic of); Lee, Haeng Jung; Lee, Eun Jung; Kim, Seog Young [Asan Medical Center, Institute for Innovative Cancer Research, Seoul (Korea, Republic of); Jang, Se Jin [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Jin; Ryu, Jin-Sook; Moon, Dae Hyuk [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2014-07-15

    Thymidine phosphorylase (TP), a key enzyme in the pyrimidine nucleoside salvage pathway, catalyses the reversible phosphorylation of thymidine, thereby generating thymine and 2-deoxy-D-ribose-1-phosphate. By regulating the levels of endogenous thymidine, TP may influence [{sup 18}F]fluorothymidine ([{sup 18}F]FLT) uptake. We investigated the effect of TP activity on [{sup 18}F]FLT uptake by tumours. Uptake of [{sup 3}H]FLT and [{sup 3}H]thymidine ([{sup 3}H]Thd) and the activities of TP, thymidine kinase 1 (TK1), and equilibrative nucleoside transporter 1 (ENT1) were determined in exponentially growing A431, A549, HT29, HOP92, ACHN, and SKOV3 cells in the presence or absence of tipiracil hydrochloride, a TP inhibitor. Eighty-five non-small cell lung cancer tissues from a patient cohort that was previously studied with [{sup 18}F]FLT positron emission tomography (PET) were retrieved and subjected to immunohistochemical analysis of TP expression. Factors that affected the maximum standardised uptake value (SUVmax) of [{sup 18}F]FLT-PET were identified by multiple linear regression analysis. A431 cells had the highest TP activity; A549 and HT29 cells had moderate TP activity; and ACHN, SKOV3, and HOP92 cells had little detectable TP activity. Cell lines with high TP activity took up more [{sup 3}H]FLT than [{sup 3}H]Thd, whereas cells with little TP activity took up more [{sup 3}H]Thd than [{sup 3}H]FLT. In cells with high TP activity, TP inhibition decreased [{sup 3}H]FLT uptake and increased [{sup 3}H]Thd uptake. However, TP inhibition had no effect on ACHN, SKOV3, and HOP92 cells. TP inhibition did not change TK1 or ENT1 activity, but did increase the intracellular level of thymidine. The SUVmax of [{sup 18}F]FLT was affected by three independent factors: Ki-67 expression (P < 0.001), immunohistochemical TP score (P < 0.001), and tumour size (P = 0.015). TP activity influences [{sup 18}F]FLT uptake, and may explain preferential uptake of [{sup 18}F]FLT over [{sup 3

  9. Catabolism of exogenously supplied thymidine to thymine and dihydrothymine by platelets in human peripheral blood

    International Nuclear Information System (INIS)

    Pero, R.W.; Johnson, D.; Olsson, A.

    1984-01-01

    The interference of platelets with the estimation of unscheduled DNA synthesis in human peripheral mononuclear leukocytes following genotoxic exposure was studied. A 96% reduction in the unscheduled DNA synthesis value was achieved by incubating [ 3 H]thymidine with platelet-rich plasma for 5 hr at 37 degrees. Using radioactive thymine-containing compounds, together with quantitative analyses based on thin-layer and ion-exchange chromatographies, we have shown that thymidine was converted to thymine which, in turn, was converted to dihydrothymine in platelet-rich plasma. The enzymes responsible were separated from platelet lysates by gel filtration and were identified as thymidine phosphorylase and dihydrothymine dehydrogenase. The phosphorylase reversibly catalyzed the formation of thymine from thymidine and converted bromodeoxyuridine to bromouracil. The dehydrogenase reversibly catalyzed the interconversion of thymine and dihydrothymine in a reaction dependent on NADP(H), and it was inhibited by diazouracil and by thymine. Nearly all the thymidine-catabolizing activity found in whole blood samples supplied exogenously with thymidine was accounted for by the platelets. Since most genetic toxicological tests that use blood samples do not involve removing platelets from the blood cell cultures, then it is concluded that precautions should be taken in the future to determine the influence of platelets on these test systems. This is particularly true for methods dependent on thymidine pulses such as unscheduled DNA synthesis, or those dependent on bromodeoxyuridine, such as sister chromatid exchanges, since this nucleoside is also a substrate for thymidine phosphorylase

  10. Clinical Value of Thymidine Kinase in Predicting Recurrence of Breast Cancer in Postsurgical Follow up Studies

    Czech Academy of Sciences Publication Activity Database

    Karlíček, V.; Topolčan, O.; Pecen, Ladislav; Eben, Kryštof; Valenta, J.; Suvová, B.

    1995-01-01

    Roč. 10, č. 2 (1995), s. 80 ISSN 0886-3849. [International Conference on Human Tumor Markers /12./. 11.06.1995-14.06.1995, New York] R&D Projects: GA AV ČR IAA230106 Keywords : medical informatics * oncology

  11. Studies of the cytosolic thymidine kinase in human cells and comparison to the recombinantly expressed enzyme

    DEFF Research Database (Denmark)

    Kock Jensen, Helle

    by recombinant technics to examine the relation between the TKl gene and the TKl protein. In the second part of this investigation a direct expression system for human TKl in E.coli was developed to produce a source of high amounts of TKl, to be able to examine the structure of TKl. The resulting recombinant TKl...... cells and that this modification can not be performed in E.coli....

  12. Transplantation of photoreceptors labeled with tritiated thymidine into RCS rats

    International Nuclear Information System (INIS)

    Gouras, P.; Du, J.; Gelanze, M.; Kwun, R.; Kjeldbye, H.; Lopez, R.

    1991-01-01

    Tritiated thymidine was administered to newborn rats to label photoreceptors, about 50% of which are still dividing. These photoreceptors were enzymatically dissociated and separated from the remainder of the retina after the infant rat matured. These labeled photoreceptors were then transplanted into a foreign host retina in the region of the outer nuclear layer. The hosts were ocular, albinotic, Royal College of Surgeons (RCS) rats, congenic to the normal donors and at least 4 months old, a time when virtually all the photoreceptors have degenerated from their retinas. The transplant site was examined at various times after transplantation by light microscope autoradiography. Labeled photoreceptor cell bodies were found in clusters in the outer nuclear layer region for as long as 3 months after transplantation surgery

  13. Associations between family suicide and personal suicidal ...

    African Journals Online (AJOL)

    The mean age was 13.3 years (range 13–15 years). There were significant associations between family suicide and students' self-reported involvement in physical fights, use of alcohol and concerns about physical health. Family suicide was associated with personal suicidal ideation, suicidal plans and suicide attempts.

  14. Teen Suicide

    Science.gov (United States)

    ... you believe your teen is at risk of suicide. Two common tests are the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory (BDI). These tests measure type, start, length, ...

  15. Transcriptional profiling of thymidine-producing strain recombineered from Escherichia coli BL21

    Directory of Open Access Journals (Sweden)

    Jin-Sook Kim

    2015-12-01

    Full Text Available DNA microarrays were used to compare the expression profiles of a thymidine overproducing strain (BLT013 and its isogenic parent, Escherichia coli BL21(DE3, when each was grown under well-defined thymidine production conditions with glycerol as carbon source. Here we describe the experimental procedures and methods in detail to reproduce the results and provide resource to be applied to similar engineering approach (available at Gene Expression Omnibus database under GSE69963. Taken together, the microarray data provide a basis for new testable hypotheses regarding enhancement of thymidine productivity and attaining a more complete understanding of nucleotide metabolism in bacteria.

  16. Liquid scintillation counting of 3H-thymidine incorporated into rat lens DNA

    International Nuclear Information System (INIS)

    Soederberg, P.G.; Lindstroem, B.

    1990-01-01

    DNA synthesis in the lens has previously been localized by autoradiography following incorporation of 3 H-thymidine. For the quantification of DNA synthesis in the lens, pooling of lenses and extraction of the DNA for liquid scintillation counting, has formerly been adapted. In the present investigation a method has been developed for the extraction of the unincorporated tracer from whole lenses after short time incubation in a medium containing 3 H-thymidine. The 3 H-thymidine incorporated into individual lenses was then detected by liquid scintillation counting after dissolution of the lenses. The sources of the variation in the method are evaluated. (author)

  17. Dual monitoring using {sup 124}I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T. S.; Kim, J. H.; Kwon, H. C. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[{sup 124}I] iodouracil ({sup 124}I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ({sup 124}I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, {sup 124}I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, {sup 124}I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by {sup 124}I-FIAU PET imaging. {sup 124}I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. {sup 124}I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials.

  18. The influence of metronidazole on free thymidine content of blood serum of irradiated mice

    International Nuclear Information System (INIS)

    Konov, A.V.; Ryabchenko, N.I.

    1986-01-01

    The influence of a radiosensitizer, metronidazole, on the free thymidine content of blood serum of irradiated mice was studied in aerobic and hypoxic conditions. A heated metronidazole solution (1 mg/g) was administered intraperitoneally 30 min before irradiation of animals with a dose of 3 Gy. Thymidine concentration in blood serum was determined by the radioimmunological technique. The influence of metronidazole on the level of thymidinemia was only noted in the animals exposed under hypoxic conditions

  19. Epidemiology of youth suicide and suicidal behavior.

    Science.gov (United States)

    Cash, Scottye J; Bridge, Jeffrey A

    2009-10-01

    Suicide is the third leading cause of death among young people in the U.S. and represents a significant public health problem worldwide. This review focuses on recent developments in our understanding of the epidemiology and risk factors for adolescent suicide and suicidal behavior. The suicide rate among children and adolescents in the U.S. has increased dramatically in recent years and has been accompanied by substantial changes in the leading methods of youth suicide, especially among young girls. Much work is currently underway to elucidate the relationships between psychopathology, substance use, child abuse, bullying, internet use, and youth suicidal behavior. Recent evidence also suggests sex-specific and moderating roles of sex in influencing risk for suicide and suicidal behavior. Empirical research into the causal mechanisms underlying youth suicide and suicidal behavior is needed to inform early identification and prevention efforts.

  20. Cell suicide

    International Nuclear Information System (INIS)

    May, E.; Coffigny, H.

    2000-01-01

    In the fight of the cell against the damages caused to its DNA by genotoxic agents and specially by ionizing radiations, the p53 protein plays a central part. It intervenes in the proliferation control and the differentiation but also in the keeping of genome integrity. It can direct the damages cells toward suicide, or apoptosis, to avoid the risk of tumor appearance that would be fatal to the whole organism. That is by the disordered state of cells suicide programs that the tumor cells are going to develop. The knowledge of apoptosis mechanisms, to eventually start them on demand, rises up broad hopes in the cancer therapy. (N.C.)

  1. Calculation of cell production from [3H]Thymidine incorporation with freshwater bacteria

    International Nuclear Information System (INIS)

    Smits, J.D.; Riemann, B.

    1988-01-01

    The conversion factor for the calculation of bacterial production from rates of [ 3 H]thymidine incorporation was examined with diluted batch cultures of freshwater bacteria. Natural bacterial assemblages were grown in aged, normal, and enriched media at 10 to 20 degree C. The generation time during 101 growth cycles covered a range from 4 to >200 h. The average conversion factor was 2.15 x 10 18 cells mol -1 of thymidine incorporated into the trichloroacetic acid (TCA) precipitate, when the generation time exceeded 20 h. At generation times of 18 cells mol -1 of thymidine incorporated into TCA precipitate. The amount of radioactivity in purified DNA increased with decreasing generation time and increasing conversion factor (calculated from the TCA precipitate), corresponding to a decrease in the percentage in protein. The conversion factors calculated from purified DNA or from the TCA precipitate gave the same variability. Conversion factors did not change significantly with the medium, but were significantly higher at 20 degree C that at 15 and 10 degree C. Results suggests that incorporation of [ 3 H]thymidine into DNA is probably limited by uptake during period with generation times of 18 cells mol -1 of thymidine incorporated is used

  2. Suicide and Murder-Suicide Involving Aircraft.

    Science.gov (United States)

    Kenedi, Christopher; Friedman, Susan Hatters; Watson, Dougal; Preitner, Claude

    2016-04-01

    This is a systematic review of suicide and homicide-suicide events involving aircraft. In aeromedical literature and in the media, these very different events are both described as pilot suicide, but in psychiatry they are considered separate events with distinct risk factors. Medical databases, internet search engines, and aviation safety databases were searched in a systematic way to obtain relevant cases. Relevant articles were searched for additional references. There were 65 cases of pilot suicide and 6 cases of passengers who jumped from aircraft found. There were also 18 cases of homicide-suicide found involving 732 deaths. Pilots perpetrated 13 homicide-suicide events. Compared to non-aviation samples, a large percentage of pilot suicides in this study were homicide-suicides (17%). Homicide-suicide events occur extremely rarely. However, their impact in terms of the proportion of deaths is significant when compared to deaths from accidents. There is evidence of clustering where pilot suicides occur after by media reports of suicide or homicide-suicide. Five of six homicide-suicide events by pilots of commercial airliners occurred after they were left alone in the cockpit. This, along with a sixth incident in which active intervention by a Japan Air crew saved 147 lives, suggests that having two flight members in the cockpit is potentially protective. No single factor was associated with the risk for suicide or homicide-suicide. Factors associated with both events included legal and financial crises, occupational conflict, mental illness, and relationship stressors. Drugs and/or alcohol played a role in almost half of suicides, but not in homicide-suicides.

  3. Suicidal behavior and assisted suicide in dementia.

    Science.gov (United States)

    Draper, Brian M

    2015-10-01

    Concerns about suicide risk in people with dementia have been increasing in recent years along with a discourse about rational suicide and assisted suicide. A systematic narrative literature review of suicidal behavior and assisted suicide in persons with dementia. Most studies that have examined the spectrum of suicidal ideation, attempted suicide and suicide in dementia have methodological limitations but the overall suicide risk does not appear to be increased. When suicidal behavior does occur, common themes include the presence of psychiatric comorbidity, mainly depression; occurrence early in the dementia course with preserved insight and capacity; and an increased risk in younger people. The emerging discourse on rational and assisted suicide has been spurred by early and pre-symptomatic diagnosis and poses a number of ethical challenges for clinicians including the role of proxy decision-makers. Although dementia might not confer a significant overall risk for suicidal behavior, clinicians still need to consider the potential for suicide in vulnerable individuals particularly early in the dementia course.

  4. Radiation doses to the tissues of rat from tritiated thymidine administered by three different routes

    International Nuclear Information System (INIS)

    Takeda, Hiroshi; Iwakura, Tetsuo; Mabuchi, Yasuo.

    1984-01-01

    Biological behaviour of tritiated thymidine were investigated in rat over 120 days after oral, intraperitoneal or intravenous administration and the absorbed doses to different tissues were estimated. The result of present study revealed that the absorbed dose from tritiated thymidine varied with the route of administration. Among the three routes of administration, intraperitoneal injection gave the highest dose to all of the tissues examined. A significant difference due to the route of administration was found in spleen and small intestine, where the doses were, respectively, 3.3 and 4.5 times higher after intraperitoneal injection than after oral ingestion. The difference was substantially dependent on the dose value from non-volatile tritium which would be incorporated into DNA. Present observation suggests that the radiation hazards of tritiated thymidine differ depending on the route of entry into the body. (author)

  5. Somatic mutation and neoplastic transformation induced by [methyl-3H]thymidine

    International Nuclear Information System (INIS)

    Lin, S.L.; Takii, M.; Ts'o, P.O.P.

    1982-01-01

    A system for the study of neoplastic transformation as induced by the incorporation of [methyl- 3 H]thymidine is described. Normal diploid golden Syrian hamster embryo fibroblasts were exposed to [methyl- 3 H]thymidine for 17 hr, followed by a brief chase with deoxycytidine- and thymidine-containing growth medium. Analysis of cell curves suggested multihit mechanism with D/sub q/ and D/sub o/ equal to 0.012 and 0.04 μCi/ml, respectively. Transformation studies demonstrate that expression of specific neoplastic phenotypes occurs at different post-treatment population doublings (PTPD), beginning with morphological alteration (PTPD 3-4), followed by enhanced fibrinolytic activity (PTPD 11-16) and the ability to clone in both medium containing 1% serum (PTPD 18-32) and soft agar (PTPD 25-32). All treated lines displayed tumorigenicity when examined at PTPD 46, whereas control cultures did not. Two tumor lines obtained from tumor explants were further characterized. Cells treated with equivalent tritium concentrations of [5- 3 H]uridine display neither elevated somatic mutation nor enhanced morphological transformation. DNA damage occurring as a result of [ 3 H]thymidine incorporation was shown via mutagenicity studies at loci coding for hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) (HPRT) and the NA + /K + ATPase (EC 3.6.1.3). [methyl- 3 H]thymidine incorporation resulted in induction of HPRT but not ouabain-resistant mutants. Present studies substantiate the importance of specific DNA/nuclear damage, induced by incorporation of tritiated thymidine, as a cause of neoplastic transformation

  6. Associations between family suicide and personal suicidal ...

    African Journals Online (AJOL)

    Associations between family suicide and personal suicidal behaviour among youth in KwaZulu-Natal, South Africa. ... Higher scores were reported on the scales assessing depression, perceived stress and feelings of hopelessness by those having had a family member commit suicide. There were low scores for having a ...

  7. Tritiated thymidine uptake in chondrocytes of chickens afflicted with tibial dyschondroplasia

    International Nuclear Information System (INIS)

    Gay, C.V.; Leach, R.M.

    1985-01-01

    3 H-Thymidine was localized in sections of growth-plate cartilage and associated tibial dyschondroplastic lesion by autoradiography. One hour after 3 H-thymidine was injected, radioactivity was found in the proliferating zone; after 48 hr it was also in the hypertrophic zone, and by 96 hr it was present in cells that were 4 to 5 mm into the lesion. This indicates that the lesion develops from the growth plate itself. The life span of the cells in the growth plate appears to be about 48 hr

  8. [Suicide in adolescence].

    Science.gov (United States)

    Tubiana, Alexandra; Cohen, Renaud F; Kahn, Jean-Pierre

    2017-04-01

    On average, in one year in France, six in every thirty teenagers have suicidal thoughts and two attempt suicide. At this age, suicidal behaviour is structured around psychopathological, developmental and relational dimensions. Talking about suicide helps to avoid it but educating teenagers in mental health is the best way of preventing this definitive act. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. TOWARD SUICIDE PREVENTION

    OpenAIRE

    Rao, Venkoba A.

    1999-01-01

    Suicide is an important mode of death. There are many psychiatrically ill patients in therapy running different degree of suicide risk. The risk of death by suicide is with almost all psychiatric illnesses, but it is found more with depressive disease, schizophrenia and personality disorder. Many studies have reported higher incidences of suicide attempts and suicide among alcoholics, which is often precipitated by family crises. Drug problems, low threshold for tolerance of day to day frustr...

  10. [Suicide and suicide tendencies in adolescent detainees].

    Science.gov (United States)

    Radeloff, Daniel; Lempp, Thomas; Rauf, Amna; Bennefeld-Kersten, Katharina; Kettner, Mattias; Freitag, Christine M

    2016-01-01

    Following accidents, suicide is the second leading cause of death in adolescence. This stage of life has the most suicide attempts of all age groups. In addition to mentally ill juveniles, adolescent delinquents represent a high-risk group for suicidal behavior and completed suicide. In particular, the population of detainees, an extreme form of juvenile delinquency, have a 16- to 18-fold higher risk of suicidal behavior and suicide compared to the general population. Because the composition of juvenile detainees differs greatly from that of detained adults, age-specific scientific approaches and prevention programs are needed. This task cannot be addressed by juvenile detention staff alone, but rather demands close cooperation between adolescent psychiatrists, psychologists, prison medical staff, legal experts and prison officers to use the opportunity for suicide prevention in juvenile detention facilities.

  11. Tritiated uracil, tritiated thymidine, and bromodeoxyuridine induced mutations in eucaryotic cells

    International Nuclear Information System (INIS)

    Burki, H.J.; Moustacchi, E.; Cleaver, J.E.

    1979-02-01

    The induction of gene conversion at the ARG-4 locus in strain BZ34 of Saccharomyces cerevisiae was examined after the cells incorporated y- 3 H uracil under optimum growth conditions for 16 hours, and then received damage at 4 0 C from tritium decays at very low dose rates of 1.4 to 27.6 tritium decays per hour. The results were compared to the results of gene conversion induced by 60 Co. The induction of resistance to 6TG in Chinese hamster ovary (CHO) cells has been studied after incorporation of 3 H-methyl thymidine, 6- 3 H-thymidine, and bromodeoxyuridine under several experimental conditions. The induction of mutations by incorporated 6- 3 H-thymidine is about three times as effective as the induction of mutations by tritiated-methyl thymidine. These results suggest that the determination of the RBE for tritium decays in model eucaryotic systems like yeast and cultured Chinese hamster cells will be influenced by the precise experimental conditions employed. In particular, experiments with mammalian cells will be affected by hot times for mutagenesis in the cell cycle and hot positions within the DNA in the nucleus, and also by the position of tritium decay within the DNA-incorporated molecule

  12. Microwave-assisted synthesis and biological evaluation of novel uracil derivatives inhibiting human thymidine phosphorylase.

    Science.gov (United States)

    Corelli, Federico; Botta, Maurizio; Lossani, Andrea; Pasquini, Serena; Spadari, Silvio; Focher, Federico

    2004-12-01

    New 5-chloro-6-substituted-uracil derivatives have been prepared by microwave assisted-synthesis and tested in vitro as thymidine phosphorylase inhibitors. One of these compounds showed potent inhibitory activity, with an IC50 value in the submicromolar range. The biological activity of the new compounds is discussed in terms of structure-activity relationship.

  13. Current Suicide Proneness and Past Suicidal Behavior in Adjudicated Adolescents

    Science.gov (United States)

    Langhinrichsen-Rohling, Jennifer; Lamis, Dorian A.

    2008-01-01

    Youth recently assigned to probation (n = 233) were assessed for current suicide proneness, depression, and hopelessness, as well as for recent suicide ideation, previous suicide ideation, or suicide attempt(s). The Life Attitudes Schedule-Short Form (LAS-SF) was used to assess suicide proneness. As per the LAS-SF, suicide proneness was defined…

  14. Triggering of Suicidal Erythrocyte Death by Gefitinib

    OpenAIRE

    Abdulla Al Mamun Bhuyan; Teresa Wagner; Hang Cao; Florian Lang

    2017-01-01

    Background/Aims: The epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib is effective against several malignancies and is mainly utilized in the treatment of epidermal growth factor receptor mutation positive non-small cell lung cancer. The anti-cancer effect of the drug involves stimulation of apoptosis. Side effects of gefitinib include anemia. At least in theory, the development of anemia during gefitinib treatment could result from triggering of eryptosis, the suicidal er...

  15. Suicide announcement on Facebook.

    Science.gov (United States)

    Ruder, Thomas D; Hatch, Gary M; Ampanozi, Garyfalia; Thali, Michael J; Fischer, Nadja

    2011-01-01

    The media and the Internet may be having an influence on suicidal behavior. Online social networks such as Facebook represent a new facet of global information transfer. The impact of these online social networks on suicidal behavior has not yet been evaluated. To discuss potential effects of suicide notes on Facebook on suicide prevention and copycat suicides, and to create awareness among health care professionals. We present a case involving a suicide note on Facebook and discuss potential consequences of this phenomenon based on literature found searching PubMed and Google. There are numerous reports of suicide notes on Facebook in the popular press, but none in the professional literature. Online social network users attempted to prevent planned suicides in several reported cases. To date there is no documented evidence of a copycat suicide, directly emulating a suicide announced on Facebook. Suicide notes on online social networks may allow for suicide prevention via the immediate intervention of other network users. But it is not yet clear to what extent suicide notes on online social networks actually induce copycat suicides. These effects deserve future evaluation and research.

  16. Suicide in the Middle Years

    Science.gov (United States)

    Coombs, David W.; Hodges, Debra K.; Kohler, Connie

    2012-01-01

    This article presents an overview of adult suicide in the United States and Alabama. This includes the latest available information on the prevalence of suicide in the US and Alabama, demographic characteristics of suicide victims, trends in suicide, and known reasons behind adult suicide. With respect to adult suicide in Alabama, it focuses on…

  17. Understanding Homicide-Suicide.

    Science.gov (United States)

    Knoll, James L

    2016-12-01

    Homicide-suicide is the phenomenon in which an individual kills 1 or more people and commits suicide. Research on homicide-suicide has been hampered by a lack of an accepted classification scheme and reliance on media reports. Mass murder-suicide is gaining increasing attention particularly in the United States. This article reviews the research and literature on homicide-suicide, proposing a standard classification scheme. Preventive methods are discussed and sociocultural factors explored. For a more accurate and complete understanding of homicide-suicide, it is argued that future research should use the full psychological autopsy approach, to include collateral interviews. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Suicide and sensibility.

    Science.gov (United States)

    Tatz, Colin

    2017-09-01

    Suicide is a domain of darkness. Entrenched in the biomedical world, suicide is commonly addressed as a complication of mental illness-usually depression-regardless of historic and social contexts, factors critical in Australian Aboriginal suicide. Prevention programs disappoint, partly because they don't differentiate between suicide categories in their strategies. Furthermore, statistics are unreliable, and underreporting remains idiosyncratic despite improved coronial practices. Unhelpfully, coroners may not presume suicide. Critical suicidology is addressing the "science" of suicide, its social significance, the contextual factors, and the reporting problems; it also proposes a sensible rethinking of attitudes toward, and education about, this taboo-laden topic.

  19. Suicide and cognitive distortions

    Directory of Open Access Journals (Sweden)

    Éva Jekkel

    2004-05-01

    Full Text Available The process of preventing suicidal acts has been studied thoroughly. There are few studies concerning cognitive mechanisms preceding suicidal actions. Suicidal behaviour consists of complexity of biological, psychological, and social factors. The transition of these factors to suicide attempt appears to be determined by cognitive processes. In this article the authors give a short review of relevant literature. To answer the question whether there are specific suicidal cognitive distortions, the authors compared a group of suicidal patients with a matched control group. In the last section of the paper they analyse their data obtained by comparing the two groups using a set of tests.

  20. Toward suicide prevention.

    Science.gov (United States)

    Rao, V A

    1999-10-01

    Suicide is an important mode of death. There are many psychiatrically ill patients in therapy running different degree of suicide risk. The risk of death by suicide is with almost all psychiatric illnesses, but it is found more with depressive disease, schizophrenia and personality disorder. Many studies have reported higher incidences of suicide attempts and suicide among alcoholics, which is often precipitated by family crises. Drug problems, low threshold for tolerance of day to day frustration, unemployement and poor parenting are major causes for youth suicide.There is biological evidence of suicidal behaviour. Fall in the level of serotonin and 5-HIAA in the CSF and in hind brain is found in subjects dying from suicide. Researchers have found decreased melatonin level in depression and suicide attempters. Long term therapy with antidepressants (Tricyclics), mood stabilizers (lithium and valproate) and new SSRIs prevent relapses and lessen suicide. It was concluded that general hospital doctors are in position of reducing suicide rates. Education of physician in detection of depression and suicide prevention will result in decline in number of suicides. The important measures include limiting the ability of methods of self-harm, antidepressants, paracetamol and insecticides.

  1. Suicide in schizophrenia.

    Science.gov (United States)

    Carlborg, Andreas; Winnerbäck, Kajsa; Jönsson, Erik G; Jokinen, Jussi; Nordström, Peter

    2010-07-01

    Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.

  2. Terrorists and Suicide Attacks

    National Research Council Canada - National Science Library

    Cronin, Audrey K

    2003-01-01

    Suicide attacks by terrorist organizations have become more prevalent globally, and assessing the threat of suicide attacks against the United States and its interests at home and abroad has therefore...

  3. Teen Suicide and Guns

    Science.gov (United States)

    ... Health Issues Listen Text Size Email Print Share Teen Suicide and Guns Page Content Article Body Protect ... thinking of a passing problem, not the outcome! Teen Suicide—A Big Problem Suicide is one of ...

  4. Schizophrenia and Suicide

    Directory of Open Access Journals (Sweden)

    Ozlem Cetin

    2011-12-01

    Full Text Available Suicide is one of the major causes of premature death among patients with schizophrenia. Follow-up studies have estimated that 4-5% of these patients die by suicide. Reducing the high rates of suicide in schizophrenia is possible with understanding of predictive risk factors. Various studies have identified risk factors for suicide in schizophrenia patients. Clinical risk factors include previous suicide attempts, comorbid depression, feelings of hopelessness, concept of insight and substance abuse. Biopsychosocial factors, such as a high intelligence quotient and high level of premorbid functioning, have also been associated with an increased risk of suicide in patients with schizophrenia. The risk of suicide is considered to be highest in the early course of illness. Antipsychotic drugs, in particular clozapine and antidepressants may be helpful in reducing the risk of suicide in schizophrenia.

  5. National Suicide Prevention Lifeline

    Science.gov (United States)

    ... Our Crisis Centers Stories of Hope and Recovery Mental Health & Suicide Prevention Glossary Get Involved Participate Our Crisis Centers Social Media Hub Promote National Suicide Prevention Month Providers & Professionals ...

  6. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...... for treatment for the relatives. In the wake of this policy document a national organization for relatives after suicide and a national network for those who attempt suicide occurred. Both organizations are formed by voluntary subscription and both organizations offer acute emergency relief, conversation groups...

  7. Kinases and Cancer.

    Science.gov (United States)

    Cicenas, Jonas; Zalyte, Egle; Bairoch, Amos; Gaudet, Pascale

    2018-03-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...].

  8. Kinases and Cancer

    OpenAIRE

    Jonas Cicenas; Egle Zalyte; Amos Bairoch; Pascale Gaudet

    2018-01-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...

  9. In vivo evaluation of the 3-carboranyl thymidine analogue (3-CTA), N5-2OH, for neutron capture therapy

    International Nuclear Information System (INIS)

    Barth, Rolf F.; Yang, Weilian; Wu, Gong; Byun, Youngjoo; Tjarks, Werner; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

    2006-01-01

    The purpose of the present study was to evaluate a 3 CTA, designated N5-2OH, as a boron delivery agent for NCT. Target validation was established using the thymidine kinase 1 (+) wild type L929 cell line and its TK1(-) counterpart, which were implanted subcutaneously into NIH nu/nu mice. 10 B-enriched N5-2OH, solubilized in DMSO (50μg 10 B in 15μl), was administered by 2 intratumoral (i.t.) injections at 2 h intervals. Two hours later the animals were irradiated at the MITR-II Research Reactor, following which tumor volumes were determined over a period of 30 days. Mice bearing TK1(+) wild type tumors, which had received N5-2OH, had a 15 fold inhibition in tumor growth compared to TK1(-) controls (247 versus 3,603 mm 3 ). Based on these data, biodistribution and therapy studies were initiated in F98 glioma bearing rats. Animals received 500μg of N5-2OH, administered intracerebrally (i.c.) by convection enhanced delivery (CED) using ALZET pumps (8μl/h for 24 h). The tumor boron concentration was 17.3μg/g compared to undetectable amounts in normal brain and blood. BNCT was carried out 14 d following i.c. implantation of 10 3 F98 glioma cells and 24 h following CED of N5-2OH (500μg/200μl). The mean survival time (MST) of these animals was 38 d compared to 31 d and 25 d, respectively, for irradiated and untreated controls. Studies are planned to optimize the delivery and formulation of N5-2OH and additional therapy studies will be carried out using N5-2OH in combination with BPA and BSH. (author)

  10. Preventing Adolescent Suicide.

    Science.gov (United States)

    Capuzzi, David

    The adolescent at risk for suicidal preoccupation and behavior has become an increasing concern for schools and communities. This paper presents some of the causes of teen suicide, things adults should know about adolescent suicide prevention, and what can be done to help such youth. The transition to adolescence is a complex time when many values…

  11. [Improving suicide prevention].

    Science.gov (United States)

    Debout, Michel

    2017-04-01

    Suicidal thoughts precede a suicide attempt. Knowing the people who are exposed to such thoughts enables prevention to be improved. The results of a study of the general population show that one in five French people claim to have already seriously considered committing suicide. This represents a particularly concerning public health issue. Copyright © 2017. Published by Elsevier Masson SAS.

  12. African American Suicide

    Science.gov (United States)

    African American Suicide Fact Sheet Based on 2012 Data (2014) Overview • In 2012, 2,357 African Americans completed suicide in the U.S. Of these, 1,908 (80. ... rate of 9.23 per 100,000). The suicide rate for females was 1.99 per 100, ...

  13. College Student Suicide

    Science.gov (United States)

    Taub, Deborah J.; Thompson, Jalonda

    2013-01-01

    Suicide is the second-leading cause of death among college students, and it is estimated that 1,088 college students die by suicide each year (National Mental Health Association and the Jed Foundation, 2002). This chapter presents the context of college student mental health within which the problem of college student suicide is situated. Because…

  14. Suicide Clusters and Contagion

    Science.gov (United States)

    Zenere, Frank J.

    2009-01-01

    Youth suicide is one of the most serious preventable health problems in the United States. It is the third leading cause of death among adolescents. According to a recent national survey of students in grades 9-12, nearly 15% of respondents had seriously considered suicide and 7% actually had attempted suicide in the previous 12 months. Moreover,…

  15. Suicide. Useful Information on...

    Science.gov (United States)

    Moore, Pamela S.; Lewis, Dorothy B., Ed.

    This booklet was written to provide information on suicide. It begins with a brief explanation of the role of suicide in history. A section describing those who commit suicide looks at various populations: elderly persons, children, adolescents and young adults, males, females, blacks, and persons of different marital status. The next section…

  16. Estrogen-progestin pharmacodynamics of the postmenopausal endometrium studied by thymidine labeling

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, E.R.; Meyer, J.S.

    1982-06-01

    Five postmenopausal women were treated with conjugated equine estrogens, 1.25 mg tablets for 25 days, and medroxyprogesterone acetate, 10 mg tablets, in combination with the last 10 estrogen doses. Twenty-five endometrial biopsy specimens were incubated in vitro with tritiated thymidine and radioautographic slides were prepared. Within five days of estrogen treatment the thymidine labeling index (TLI) in both glands and stromal cells increased from a very low resting state to relatively high levels of DNA synthesis and cell proliferation. Within five days after addition of progestin, epithelial TLIs decreased to low levels and returned to minimal baseline levels four days after the last steroid dose. Analysis of variances indicated significant changes in epithelial cells (P less than 0.0001) confirming that the proliferative effect of estrogens was suppressed during the progestin phase. Stromal TLI changes were not significant (P . 0.46).

  17. Estrogen-progestin pharmacodynamics of the postmenopausal endometrium studied by thymidine labeling

    International Nuclear Information System (INIS)

    Friedrich, E.R.; Meyer, J.S.

    1982-01-01

    Five postmenopausal women were treated with conjugated equine estrogens, 1.25 mg tablets for 25 days, and medroxyprogesterone acetate, 10 mg tablets, in combination with the last 10 estrogen doses. Twenty-five endometrial biopsy specimens were incubated in vitro with tritiated thymidine and radioautographic slides were prepared. Within five days of estrogen treatment the thymidine labeling index (TLI) in both glands and stromal cells increased from a very low resting state to relatively high levels of DNA synthesis and cell proliferation. Within five days after addition of progestin, epithelial TLIs decreased to low levels and returned to minimal baseline levels four days after the last steroid dose. Analysis of variances indicated significant changes in epithelial cells (P less than 0.0001) confirming that the proliferative effect of estrogens was suppressed during the progestin phase. Stromal TLI changes were not significant

  18. Incorporation of tritiated thymidine and uridine in normal and endopolyploid nuclei of differentiated tissue

    International Nuclear Information System (INIS)

    Bansal, Y.K.; Sen, Sumitra

    1987-01-01

    Rate of replication and transcription between normal and giant endopolyploid nuclei of differentiated tissue of Hordeum vulgare L. (2n=14) roots and Phlox drummondii Hook. (2n=14) and Zea mays L. (2n=20) endosperms were studied by labelling experiments with tritiated thymidine and uridine. The incorporation of thymidine and uridine was identical in both diploid and giant endopolyploid nuclei of the roots of H. vulgare. The endosperm cells of P. drummondii and Z. mays, however, exhibit markedly different labelling pattern in normal (i.e. triploid) and endopolyploid nuclei where both replication and transcription were rather high. The nutritive function of the endosperm is probably responsible for this high degree of activity. (author). 14 refs., 10 figs., 3 tables

  19. Suicide and Personality

    Directory of Open Access Journals (Sweden)

    K. Nahit Ozmenler

    2009-07-01

    Full Text Available Many factors may play role in the emergence of suicidal behavior. Familial tendency including some features of personality structure, hopelessness, affective disorder, and suicide behavior have attracted close attention recently. Personality disorders seem to be prevalent in individuals who attempt suicide. Beside it has been reported that personality disorders and other psychiatric disorder comorbidity increase the risk of suicide. To present the relationship between suicide and personality is quite important for developing strategies in order to prevent suicide attempt. In this field, the data show variability based on scales used for the evaluation of personality, its definition and classification in the research. For example, while some authors used DSM criteria or ICD criteria, others preferred to focus on the temperament and character dimensions of personality. In studies based on diagnostic criteria; B group personality disorders, such as antisocial and borderline personality disorders were found to be most common comorbid personality disorder diagnosis. In studies aiming to investigate the relationship among suicide attempt, temperament and character features, the suicide attempters were found to have lower levels of self directedness, cooperativeness, and higher scores for self transcendence. Suicidal patients were inclined to have higher scores in several temperament groups like harm avoidance, novelty seeking, and reward dependence. Tendency to impulsive behavior is reported as a common denominator for suicidal patients. Individuals, who have familial or acquired tendency of impulsivity, could react more dramatically and present with depressive and pessimistic mood when they have difficulties and encounter stress factors in their daily routine and could easily develop depressive disorders. These factors as a whole could lead to self destructive actions like suicide. Individual or familial history of suicide attempts or completed

  20. Suicide and Suicidal Behavior among Transgender Persons.

    Science.gov (United States)

    Virupaksha, H G; Muralidhar, Daliboyina; Ramakrishna, Jayashree

    2016-01-01

    Suicide rate and suicidal tendencies among transgender persons are considerably high compared to general population. Hence, this review is an attempt to understand the issues around the suicide and suicidal behavior among transgender persons. The literature search conducted using three sources, i.e., electronic databases (PubMed, ProQuest, Google Scholar, PsycInfo), manual search (library catalog), and gray literature (consultation with experts). The suicide attempt rate among transgender persons ranges from 32% to 50% across the countries. Gender-based victimization, discrimination, bullying, violence, being rejected by the family, friends, and community; harassment by intimate partner, family members, police and public; discrimination and ill treatment at health-care system are the major risk factors that influence the suicidal behavior among transgender persons. In spite of facing a number of hardships in their day-to-day life, the transgender community holds a number of resiliency factors. Further, this community needs to be supported to strengthen their resiliency factors and draw culturally sensitive and transgender-inclusive suicide prevention strategies and increase protective factors to tackle this high rate of suicidality.

  1. An integrated chemo-enzymatic route for preparation of ß-thymidine, a key intermediate in the preparation of antiretrovirals

    CSIR Research Space (South Africa)

    Gordon, GER

    2011-01-01

    Full Text Available A chemo-enzymatic method for production of ß-thymidine, an intermediate in the synthesis of antiretrovirals, is described. Guanosine and thymine were converted by means of enzymatic transglycosylation to yield 5-methyluridine (5-MU), which...

  2. Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-formylcoumarin derivatives.

    Science.gov (United States)

    Taha, Muhammad; Adnan Ali Shah, Syed; Afifi, Muhammad; Imran, Syahrul; Sultan, Sadia; Rahim, Fazal; Hadiani Ismail, Nor; Mohammed Khan, Khalid

    2018-03-01

    Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1-17) were synthesized, characterized by 1 HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC 50 values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC 50 value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. STAT3/NF-κB-Regulated Lentiviral TK/GCV Suicide Gene Therapy for Cisplatin-Resistant Triple-Negative Breast Cancer.

    Science.gov (United States)

    Kuo, Wei-Ying; Hwu, Luen; Wu, Chun-Yi; Lee, Jhih-Shian; Chang, Chi-Wei; Liu, Ren-Shyan

    2017-01-01

    Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs). In this study, we have cloned a novel STAT3/NF-κB-based reporter system to drive the expression of herpes simplex virus thymidine kinase (HSV-TK) against breast cancer. Lentiviral vector expressing HSV-TK under the regulation of STAT3/NF-κB fused response element was developed. In this setting, we exploited the constitutive STAT3/NF-κB activation in tumors to achieve higher transgene expression than that driven by a constitutively active CMV promotor in vivo . An orthotropic MDA-MB-231 triple negative breast cancer mouse model was used for evaluating the feasibility of STAT3-NF-κB-TK/GCV suicide gene therapy system. The basal promoter activity of Lenti-CMV-TK and Lenti-STAT3-NF-κB-TK in MDA-MB-231 cells was compared by 3 H-FEAU uptake assay. The Lenti-CMV-TK showed ~5 fold higher 3 H-FEAU uptake then Lenti -STAT3-NF-κB-TK. In clonogenic assay, cells expressing Lenti-CMV-TK were 2-fold more sensitive to GCV than Lenti-STAT3-NF-κB-TK transduced cells. In vitro effect of STAT3-NF-κB-induced transgene expression was determined by 10ng/mL TNF-α induction and confirmed by western blot analysis and DsRedm fluorescent microscopy. In vivo evaluation of therapeutic effect by bioluminescence and [ 18 F]FHBG microPET imaging indicated that Lenti-STAT3-NF-κB-TK showed more tumor growth retardation than Lenti-CMV-TK when GCV (20 mg/kg) was administered. The invasiveness and expression of cancer stem cell markers were both decreased after STAT3/NF-κB-regulated HSV

  4. Suicidal Behavior in Elderly

    Directory of Open Access Journals (Sweden)

    Murat Aslan

    2014-09-01

    Full Text Available The size of the elderly population is expected to increase dramatically in the next decades worldwide, also in Turkey. In accordance with these demographic changes, psychiatric disorders in late life, including suicide becomes much important. Elderly suicide is a very serious public health problem. Suicide rates in both males and females generally increase with age. However, the pattern is different in every nation. Suicidal behaviour in old age exists as a spectrum ranging from death wishes to completed suicide. Risk factors for suicide in old age are male sex, lower socioeconomic status, social isolation, having personality traits like hopelessness and dependency on others etc., the presence of psychiatric and physical disorders and previous suicidal behaviour. The most common cause for elderly suicide, as for all suicides, is untreated depression. Thus, elderly depression needs to be recognized and treated. The treatment of depressive disorder and other psychiatric diorders in late life, counselling in crisis situations and prevention of social isolation in elderly people are the major points for the prevention of suicide in old age. In this review article is to investigate the relationship between elderly and suicidal behavior. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 294-309

  5. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H

    1994-01-01

    report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes......, a candidate repressor, from the MT2 site in late G1 may be essential for S phase-dependent transcription of the mouse TK gene....

  6. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  7. A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase

    Directory of Open Access Journals (Sweden)

    Juri G. Tjuvajev

    1999-10-01

    Full Text Available Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene can be used to monitor the expression of the LacZ gene (a second gene under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.

  8. Multifactorial Causes of Suicide

    Directory of Open Access Journals (Sweden)

    Antemir Cristina-Laura

    2017-12-01

    Full Text Available The science of psychology is well placed to the advantage of understanding why some people are trying to take their lives, and others do not. Understanding the psychological processes underlying the idea of suicide and the decision to act on suicidal thoughts is particularly important. Especially since interventions should be targeted at the suicidal ideation when it first appears before it becomes an attempt of suicide. Factors associated with suicidal risk can be classified into four groups: personality and individual differences, cognitive factors, social factors and life-threatening factors. Each of these factors can contribute to the emergence of suicide risk independently or together with other factors. Some of them are associated with the emergence of suicidal ideation, while others increase the likelihood that these thoughts will come to life.

  9. Prevention of suicide

    Directory of Open Access Journals (Sweden)

    Rajiv Gupta

    2017-01-01

    Full Text Available Suicide is a major public health problem in India, probably even bigger than in the West. Suicidal behavior is the best conceptualized as a multifaceted complex problem involving social factors and mental illnesses. Broadly, there are two approaches to suicide prevention; population preventive strategies and high-risk preventive strategies. Population preventive strategies include reducing availability of means for suicide, education of primary care physicians, influencing media portrayal of suicidal behavior, education of the public, telephone helplines, and addressing economic issues associated with suicidal behavior. High-risk preventive strategy includes identifying individuals with high risk of committing suicide, intensively treating mental illness if present, and providing psychosocial support. Thus, prevention requires a multipronged effort with collaboration from various sectors including mental health professionals, social justice department, and macroeconomic policy makers.

  10. Multiple sclerosis and suicide.

    Science.gov (United States)

    Feinstein, Anthony; Pavisian, Bennis

    2017-06-01

    Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

  11. Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis.

    Science.gov (United States)

    Carlborg, Andreas; Jokinen, Jussi; Nordström, Anna-Lena; Jönsson, Erik G; Nordström, Peter

    2010-01-01

    People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor. Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide. Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records. Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters. Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.

  12. [Suicide and suicidal behaviors in Mexico: Retrospective and current status].

    Science.gov (United States)

    Borges, Guilherme; Orozco, Ricardo; Benjet, Corina; Medina-Mora, Maria Elena

    2010-01-01

    To summarize the epidemiology of completed suicide and suicidal behavior in Mexico. National data registries on mortality from the year 1970 to 2007 and cross-sectional surveys were used to analyze suicide mortality and suicidal behavior. The suicide rate grew 275% from 1970 to 2007. Suicide has been increasing among Mexicans 15-29 years old since 1970. In adults aged 18-29 years the lifetime prevalence of ideation was 9.7%, and attempt 3.8%. About 6,601,210 Mexicans had suicidal thoughts, 593,600 attempted suicide and 99,731 used some sort of medical service as a direct consequence of the latter in the year prior to the survey. Suicide and suicide-related behaviors are significant public health problems and, as such, actions are urgently required to identify and treat persons with suicidal thoughts, assess suicidal risk in patients with psychiatric disorders and implement population interventions.

  13. Suicide Mortality, Suicidal Ideation and Psychological Problems in Dutch Anaesthesiologists

    NARCIS (Netherlands)

    Liem, M.C.A.; Liem, A.L.; Dongen, van E.P.A.; Carels, I.C.; Egmond, van M.; Kerkhof, A.J.F.M.

    2015-01-01

    Previous studies reveal an elevated suicide rate for anaesthesiologists. We sought to examine anaesthesiologist suicide mortality and its underlying explanatory factors. Two studies were conducted in order to establish the suicide mortality figures among Dutch anaesthesiologists and to investigate

  14. Prioritizing Research to Reduce Youth Suicide and Suicidal Behavior

    OpenAIRE

    Bridge, Jeffrey A.; Horowitz, Lisa M.; Fontanella, Cynthia A.; Grupp-Phelan, Jackie; Campo, John V.

    2014-01-01

    The goal of the National Action Alliance for Suicide Prevention (Action Alliance) is to reduce suicide and suicide attempts in the U.S. by 40% in the next decade. In this paper, a public health approach is applied to suicide prevention to illustrate how reductions in youth suicide and suicidal behavior might be achieved by prioritizing research in two areas: (1) increasing access to primary care–based behavioral health interventions for depressed youth; and (2) improving continuity of care fo...

  15. Holiday Suicides: Fact or Myth?

    Science.gov (United States)

    ... Press Room Social Media Publications Injury Center Holiday Suicides: Fact or Myth? Recommend on Facebook Tweet Share ... Developing and evaluating prevention programs. Learn More About Suicide CDC’s Overview of Suicide CDC’s Strategic Direction for ...

  16. Hotel room suicide.

    Science.gov (United States)

    Zarkowski, Paul; Avery, David

    2006-10-01

    The objective of our research was to quantify the increased risk of suicide associated with registering in local hotels/motels. Medical examiner case files of suicide in King County, Washington, were reviewed for years 2002-2004. The incidence of suicide in local residents registering in local hotels/motels was 223/100,000 which is significantly greater than the incidence of suicide in the general population of King County (11.7/100,000 p Hotel/motel guests from outside Washington had a significantly reduced incidence of suicide (3.9/100,000 p = 0.002). The study results suggest that there is an increased risk of suicide in local residents who register in local hotel rooms.

  17. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  18. Youth Suicidal Behavior

    Science.gov (United States)

    AAS 2011 Youth Suicidal Behavior Fact Sheet 4,822 youth age 15-24 died by suicide. i We want to change that. Su icid eRat ebyRace , age s 15-24, ... often the first to know their friend is suicidal, and we need to help them know where to ... 2011 Youth Risk and Behavior Survey found that in the previous 12 months ...

  19. Financial Loss and Suicide

    OpenAIRE

    Saxby, Pridmore; Anil, Reddy

    2012-01-01

    The current Western psychiatric wisdom states that suicide is always or almost always associated with mental disorder. Careful Asian studies are casting doubt on this conclusion. Using information from the public record (newspapers, coroner’s reports, and various web-based sources), we sought evidence that, in the absence of mental disorder, suicide may be associated with major financial loss. Reports of 15 individuals who completed suicide following major financial loss were identified, thus...

  20. [Suicide, a social fact].

    Science.gov (United States)

    Baudelot, Christian

    2017-04-01

    Treating suicide as a social fact means disregarding its individual and dramatic dimensions. Sociologists do not reason on the basis of specific cases but by studying the variations, in space and time, of suicide rates. Their contribution relates essentially to a renewed perspective on society: suicide is in fact a very accurate indicator of the intensity and quality of the bonds which unite or isolate individuals in a society. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Tritium distribution in newborn mice after providing mother mice with drinking water containing tritiated thymidine

    International Nuclear Information System (INIS)

    Saito, M.; Streffer, C.; Molls, M.

    1983-01-01

    Throughout gestation pregnant mice received drinking water which contained [methyl- 3 H]thymidine (18.5 kBq/ml). The newborn mice were divided into two groups. One group was nursed by their own mothers, which were further supplied with tritiated thymidine until 4 weeks after delivery (Experiment I). The other group was nursed by ''nonradioactive mothers'' which were given no tritiated thymidine (Experiment II). Tritium incorporation into the small molecular components of the acid-soluble fraction, lipid, RNA, DNA, and protein was analyzed for the newborn mice at various ages. In Experiment II, total radioactivity per gram tissue decreased initially after birth with a half life of 2.5-2.9 days in spleen, liver, intestine, stomach, thymus, lung, kidney, heart, and brain. At about 2 weeks after birth, a slower component of tritium elimination due mainly to the DNA-bound tritium appeared. Specific activity of DNA at birth was organ specific, highest in heart and lowest in thymus. Cumulative absorbed dose in various organs was estimated for the first 4 weeks after birth based upon an assumption that total and DNA-bound tritium are uniformly distributed. The result showed that organ specificity of dose accumulation is obvious for DNA-bound tritium, highest in spleen (1.15 mGy) and lowest in brain (0.13 mGy). It was also shown that the tritium supply from mother's milk is of minor importance for dose accumulation of DNA-bound tritium in the cell nuclei of organs of suckling mice

  2. Tritium distribution in newborn mice after providing mother mice with drinking water containing tritiated thymidine

    International Nuclear Information System (INIS)

    Saito, M.; Streffer, C.; Molls, M.

    1983-01-01

    Throughout gestation pregnant mice received drinking water which contained [methyl- 3 H]thymidine (18.5 kBq/ml). The newborn mice were divided into two groups. One group was nursed by their own mothers, which were further supplied with tritiated thymidine until 4 weeks after delivery (Experiment I). The other group was nursed by nonradioactive mothers which were given no tritiated thymidine (Experiment II). Tritium incorporation into the small molecular components of the acid-soluble fraction, lipid, RNA, DNA, and protein was analyzed for the newborn mice at various ages. In Experiment II, total radioactivity per gram tissue decreased initially after birth with a half life of 2.5 to 2.9 days in spleen, liver, intestine, stomach, thymus, lung, kidney, heart, and brain. At about 2 weeks after birth, a slower component of tritium elimination due mainly to the DNA-bound tritium appeared. Specific activity of DNA at birth was organ specific, highest in heart and lowest in thymus. Cumulative absorbed dose in various organs was estimated for the first 4 weeks after birth based upon an assumption that total and DNA-bound tritium are uniformly distributed. The result showed that organ specificity of dose accumulation is obvious for DNA-bound tritium, highest in spleen (1.15 mGy) and lowest in brain (0.13 mGy). It was also shown that the tritium supply from mother's milk is of minor importance for dose accumulation of DNA-bound tritium in the cell nuclei of organs of suckling mice

  3. Comparative Study between topical applications liposomally entrapped DNA repair enzymes and thymidine dinucleotide as radioprotectors

    International Nuclear Information System (INIS)

    Shabon, M.H.; El-Bedewi, A.F.

    2005-01-01

    The delivery of active agents to the skin by liposome carriers received great interest during the last three decades. This is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Recent work suggests that liposomes as vehicles for topical drug delivery may be superior to conventional preparations. Also, topical application of DNA repair enzymes to irradiated skin increases the rate of repair of DNA potentially damaged cells. Moreover, thymidine dinucleotide is a new skin photo-protective agent against non-ionizing radiation through induction of DNA repair. Gamma irradiation can produce DNA damage in human skin. DNA mutations have an important role in the development of skin cancer and precancerous skin lesions. Albino rats were irradiated with Cobalt-60 gamma radiation with different doses (0.5, 1.5, 3 Gy), and were treated by either thymidine dinucleotide or liposomally entrapped DNA repair enzymes topically 24 hours before irradiation. Evaluation was done histopathologically by H and E stain. Computerized image analyzer using Masson's trichrome stain was also done. Gamma radiation produced epidermal thinning and dermal inflammatory cells together with collagen fragmentation and clumping in a dose-dependent manner. Comparing between both thymidine dinucleotide and liposomally entrapped DNA repair enzymes pretreated and irradiated rats. Low dose irradiation (0.5 Gy) together with previous drugs showed preservation of epidermis with no inflammatory cells and also it maintained the normal architecture of collagen bundles. However, they were ineffective with higher doses. In conclusion our results may suggest that the effects of gamma radiation on the skin at low dose could be minimized by the use of these drugs before exposure

  4. The endozepine ODN stimulates [{sup 3}H]thymidine incorporation in cultured rat astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Gandolfo, P.; Patte, C.; Thoumas, J.L.; Leprince, J.; Vaudry, H.; Tonon, M.C. [European Institute for Peptide Research (IFRMP no. 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U 413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan (France)

    1999-05-15

    High concentrations of diazepam-binding inhibitor (DBI) mRNA have been detected in astrocytoma, suggesting that DBI-derived peptides may play a role in glial cell proliferation. In the present study, we have investigated the effect of a processing product of DBI, the octadecaneuropeptide ODN, on DNA synthesis in cultured rat astrocytes. At very low concentrations (10{sup -14} to 10{sup -11} M), ODN caused a dose-dependent increase of [{sup 3}H]thymidine incorporation. At higher doses (10{sup -10} to 10{sup -5} M), the effect of ODN gradually declined. The central-type benzodiazepine receptor antagonist flumazenil (10{sup -6} M) completely suppressed the stimulatory action of ODN whereas the peripheral-type benzodiazepine receptor ligand, PK11195 (10{sup -6} M) had no effect. The ODN-induced stimulation of [{sup 3}H]thymidine incorporation was mimicked by methyl 6,7-dimethoxy-4-ethyl-{beta}-carboline-3-carboxylate (DMCM). The GABA{sub A} receptor antagonist bicuculline (10{sup -4} M) suppressed the effect of both ODN and DMCM on DNA synthesis. Exposure of cultured astrocytes to the specific GABA{sub A} agonist 3APS (10{sup -10} to 10{sup -4} M) also induced a dose-related increase of [{sup 3}H]thymidine incorporation. The present study indicates that ODN, acting through central-type benzodiazepine receptors associated with the GABA{sub A} receptor complex, stimulates DNA synthesis in rat glial cells. These data provide evidence for an autocrine role of endozepines in the control of glial cell proliferation. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. 3H-thymidine labelling pattern of preleptotene chromosone condensation stages in the foetal sheep ovary

    International Nuclear Information System (INIS)

    Luciani, J.M.; Devictor-Vuillet, Monique; Bezard, Jacqueline; Mauleon, P.

    1979-01-01

    A sequence of morphological events from premeiotic interphase to leptotene has been described in the ovaries of 64-day old sheep foetuses. The nuclear changes throughout the condensation and decondensation stages showed a sequential pattern. After a flash of tritiated thymidine, the labelling pattern of these figures demonstrated that those stages followed premeiotic DNA synthesis, i.e. belonged to meiotic prophase. However, with our methodology, this sequence of morphological events could not be confirmed due to a high asynchronism in the oogenetic processes

  6. Autoradiographic investigation of sperm transit through the male mouse genital tract after tritiated thymidine incorporation

    Energy Technology Data Exchange (ETDEWEB)

    Dadoune, J.P.; Alfonsi, M.F. (Faculte de Medecine Broussais-Hotel-Dieu, U.E.R. Biomedicale des Saints-Peres, 75 - Paris (France))

    1984-01-01

    The transit of spermatozoa in the genital tract of the male mouse was investigated by quantitative light microscopic autoradiography after intraperitoneal injection of tritiated thymidine. Transit duration in the caput and the corpus of the epididymis was shown to be 3 days; the total duration of transit in the genital tract was 5 days. These findings indicate that the time required for the transit of spermatozoa in the epididymal caput and corpus was comparable to that calculated in other mammals studied. However, the duration of sperm storage in the epididymal cauda appeared to be shorter than that previously reported for rodents.

  7. Masculinity and suicidal thinking.

    Science.gov (United States)

    Pirkis, Jane; Spittal, Matthew J; Keogh, Louise; Mousaferiadis, Tass; Currier, Dianne

    2017-03-01

    Males feature prominently in suicide statistics, but relatively little work has been done to date to explore whether endorsement of dominant masculinity norms heightens the risk of or is protective against suicidal thinking. This paper aimed to further knowledge in this area. We used baseline data from 13,884 men (aged 18-55) in the Australian Longitudinal Study on Male Health (Ten to Men) cohort. These men filled in self-complete questionnaires in 2013/14 which covered a range of topics, including conformity to dominant masculinity norms and suicidal thinking. We conducted logistic regression analyses to estimate the strength of association between these two variables. After controlling for other key predictors of suicidal thinking, one characteristic of dominant masculinity-self-reliance-stood out as a risk factor for suicidal thinking (AOR 1.34; 95% CI 1.26-1.43). It suggests that one particular element of dominant masculinity-being self-reliant-may place men at increased risk of suicidal thinking. This finding resonates with current theories of how suicidal thinking develops and leads to action. It also has implications for the full gamut of suicide prevention approaches that target males in clinical settings and in the general population, and for our broader society. Further work is needed, however, to confirm the direction of the relationship between self-reliance and suicidality, and to unpack the means through which self-reliance may exert an influence.

  8. Suicide with cesium 137

    International Nuclear Information System (INIS)

    Krushkov, I.; Vassileva, B.

    1978-01-01

    Report on first case of suicide with radioactive substance in Bulgaria is given. A defectoscopist with cyclothymic structure of character and psychotraumatic family environment made a second and successful attempt at suicide, this time by means of external irradiation with 137 Cs with an activity of 5.3 C in the course of two hours. He irradiated his heart region and the first three fingers of his right hand. A grave picture of acute, local irradiation injury lasting four months with lethal outcome. The authors treat the psychological motives in the behaviour of these suicides and the reasons which determine the small number of suicide carried out with radioactive substance. (author)

  9. Cultural aspects of suicide.

    Science.gov (United States)

    Maharajh, Hari D; Abdool, Petal S

    2005-09-08

    Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

  10. Psychological models of suicide.

    Science.gov (United States)

    Barzilay, Shira; Apter, Alan

    2014-01-01

    Suicidal behavior is highly complex and multifaceted. Consequent to the pioneering work of Durkheim and Freud, theoreticians have attempted to explain the biological, social, and psychological nature of suicide. The present work presents an overview and critical discussion of the most influential theoretical models of the psychological mechanisms underlying the development of suicidal behavior. All have been tested to varying degrees and have important implications for the development of therapeutic and preventive interventions. Broader and more in-depth approaches are still needed to further our understanding of suicidal phenomena.

  11. Schizophrenia and suicide.

    Science.gov (United States)

    Balhara, Y Ps; Verma, R

    2012-09-01

    Schizophrenia is characterised by distorted thinking and perception and tends to run a chronic course. The World Health Organization reported that suicide accounts for almost 2% of the world's deaths. There is a close relationship between schizophrenia and suicide. Patients with schizophrenia experience personal distress and socio-occupational dysfunction and reduced life expectancy as a group. The current article presents a review of suicide in schizophrenia. The literature search included MEDLINE, CINHAL, EMBASE, and Cochrane Controlled Trials Register databases. Search terms used included 'schizophrenia', 'suicide', 'positive symptoms', 'negative symptoms', 'self-harm', 'anti-psychotics', 'risk factors' in different combinations. We included epidemiological findings, socio-demographical variables, symptom profiles, biological underpinnings, risk factors, and management issues. No publication year limits were applied but the search was restricted to articles in English. The abstracts of articles retrieved in the search were manually scanned. Male gender and being unmarried are associated with an increased risk of suicide among individuals with schizophrenia. The presence of depression and depressive features is associated with an increased risk of suicidality. An association between insight into the illness, a consequent feeling of hopelessness, and increased risk of suicide has also been a consistent finding. In contrast the role of schizophrenia subtype in suicidal risk remains controversial. To date, the impact of specific pharmacotherapeutic agents and non-pharmacological interventions on the suicidal behaviour of individuals with schizophrenia is also yet to be fully explored by robust research.

  12. Modifying effect of 5-fluoro-2-deoxyuridine and thymidine at G1 phase on radiation and chemically induced chromosome rearrangement

    International Nuclear Information System (INIS)

    Azatyan, R.A.; Voskanyan, A.Z.; Avakyan, V.A.; Akif'ev, A.P.

    1978-01-01

    The yield of structural chromosome mutations induced in Crepis capillaris seeds by X-rays and nitrogen mustard was studied as a function of treatment (at G 1 phase) with an inhibitor of unscheduled DNA synthesis, 5-fluoro-2-deoxyuridine (FdU), and its antagonist, thymidine. Air-dry seeds were irradiated at 10 krad and immediately placed in aqueous solutions of FdU, thymidine, or FdU + thymidine. Ionizing radiation induced only chromosome exchanges in the seeds. When EdU was used, the number of chromosome exchanges was the same although the fraction of simple and isolocus deletions was significantly greater than additive. The effect of FdU was manifested only after 10-hour incubation of the cells. Thymidine alone did not appreciably alter the frequency of radiation-induced aberrations. At the same time, the FdU + thymidine combination decreased the mutation yield i.e. was protective. Frequencies of the chromosome aberration in this experiment were the same as in the control

  13. Suicidality in Body Dysmorphic Disorder

    Science.gov (United States)

    Phillips, Katharine A.

    2008-01-01

    Suicidal ideation, suicide attempts, and completed suicide appear common in individuals with body dysmorphic disorder (BDD). Available evidence indicates that approximately 80% of individuals with BDD experience lifetime suicidal ideation and 24% to 28% have attempted suicide. Although data on completed suicide are limited and preliminary, the suicide rate appears markedly high. These findings underscore the importance of recognizing and effectively treating BDD. However, BDD is underrecognized in clinical settings even though it is relatively common and often presents to psychiatrists and other mental health practitioners, dermatologists, surgeons, and other physicians. This article reviews available evidence on suicidality in BDD and discusses how to recognize and diagnose this often secret disorder. Efficacious treatments for BDD, ie, serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy, are also discussed. Although data are limited, it appears that SRIs often diminish suicidality in these patients. Additional research is greatly needed on suicidality rates, characteristics, correlates, risk factors, treatment, and prevention of suicidality in BDD. PMID:18449358

  14. Emile Durkheim and altruistic suicide.

    Science.gov (United States)

    Stack, Steven

    2004-01-01

    Altruistic suicides are marked by cultural approval and benefit the social order. They occur in social groups where there is a low value placed on the individual. The principle loci of altruistic suicide are primitive societies and the modern military. Subtypes of altruistic suicide (obligatory, optional, acute) are delineated and evaluated. Military suicide rates are seen as being inversely related to civilian suicide rates. Key limitations of Durkheim's model are discussed including his exaggerating the prevalence of obligatory suicide. Suggested points of departure for future research on altruistic suicide include comparative analyses of suicide in the modern military, and application of the concept of optional altruistic suicide to the impact of suicide acceptability on national suicide rates.

  15. Assessing the Effects of Peer Suicide on Youth Suicide

    Science.gov (United States)

    Feigelman, William; Gorman, Bernard S.

    2008-01-01

    Using data from all waves of the National Longitudinal Survey of Adolescent Health, we investigated the short-term and long-term impact of an adolescent friend's suicide on an adolescent's depression and suicidality. Results suggest that a friend's suicide is associated with heightened suicide thoughts and attempts and greater depression during…

  16. The kinetic mechanism of Human Thymidine Phosphorylase - a molecular target for cancer drug development.

    Science.gov (United States)

    Deves, Candida; Rostirolla, Diana Carolina; Martinelli, Leonardo Kras Borges; Bizarro, Cristiano Valim; Santos, Diogenes Santiago; Basso, Luiz Augusto

    2014-03-04

    Human Thymidine Phosphorylase (HTP), also known as the platelet-derived endothelial cell growth factor (PD-ECGF) or gliostatin, catalyzes the reversible phosphorolysis of thymidine (dThd) to thymine and 2-deoxy-α-d-ribose-1-phosphate (2dR1P). HTP is a key enzyme in the pyrimidine salvage pathway involved in dThd homeostasis in cells. HTP is a target for anticancer drug development as its enzymatic activity promotes angiogenesis. Here, we describe cloning, expression, and purification to homogeneity of recombinant TYMP-encoded HTP. Peptide fingerprinting and the molecular mass value of the homogenous protein confirmed its identity as HTP assessed by mass spectrometry. Size exclusion chromatography showed that HTP is a dimer in solution. Kinetic studies revealed that HTP displayed substrate inhibition for dThd. Initial velocity and isothermal titration calorimetry (ITC) studies suggest that HTP catalysis follows a rapid-equilibrium random bi-bi kinetic mechanism. ITC measurements also showed that dThd and Pi binding are favorable processes. The pH-rate profiles indicated that maximal enzyme activity was achieved at low pH values. Functional groups with apparent pK values of 5.2 and 9.0 are involved in dThd binding and groups with pK values of 6.1 and 7.8 are involved in phosphate binding.

  17. Register for Suicide Attempts

    DEFF Research Database (Denmark)

    Christiansen, Erik; Jensen, Børge Frank

    2004-01-01

    The Register for Suicide Attempts (RSA) is a product of the WHO research project "WHO/Euro Multicentre Study on Parasuicide", which, among other things, had the purpose of collecting data on suicide attempts from 13 European countries. Data is collected in order to calculate trends and identify...

  18. Endocrinology and Suicide.

    Science.gov (United States)

    Rich, Charles L

    1986-01-01

    Concludes that thyroid and adrenal gland disease unquestionably can produce severe mental disturbances. Most of these are "organic" in nature, but depressive symptoms are common as well. Cautions that a connection between these diseases and suicide has not been established. Advises treating all depressed, suicidal persons with the same…

  19. Depression and Suicide Risk

    Science.gov (United States)

    ... Box — Depression, Antidepressants, and the Risk of Suicide. New England Journal of Medicine, 356:2343-2346. xiii http://psychcentral.com/blog/ ... Box — Depression, Antidepressants, and the Risk of Suicide. New England Journal of Medicine, 356:2343-2346.

  20. Surviving After Suicide

    Science.gov (United States)

    ... Some Facts: Survivors of suicide represent “the largest mental health casualties related to suicide” (Edwin Shneidman, PH.D., ... times, especially if the loved one had a mental disorder, the survivor may experience relief. There is a stigma attached to suicide, partly due to the misunderstanding ...

  1. Suicide and religion.

    Science.gov (United States)

    Cook, Christopher C H

    2014-01-01

    Much of the evidence that religion provides a protective factor against completed suicide comes from cross-sectional studies. This issue of the Journal includes a report of a new prospective study. An understanding of the relationship between spirituality, religion and suicide is important in assessing and caring for those at risk.

  2. Suicide and Ethics.

    Science.gov (United States)

    Battin, Margaret P., Ed.; Maris, Ronald W., Ed.

    1983-01-01

    Presents five articles by philosophers and a psychiatrist on the ethics of suicide, as well as comments and a literature review. Discusses the rationality and morality of suicide from several philosophical viewpoints including self-ownership, Kant's theories, and a libertarian perspective. (JAC)

  3. The suicidal desire of Tolstoy.

    Science.gov (United States)

    Pridmore, Saxby; Pridmore, William

    2011-06-01

    To explore whether a healthy, successful individual may experience suicidal desires. Examination of "A Confession" by Leo Tolstoy. Confirmation that a physically and mentally healthy, well resourced individual may experience suicidal desires. To reduce suicide rates, a broader understanding of the factors which contribute to suicidal desires is required.

  4. Suicide in Batman, Southeastern Turkey

    Science.gov (United States)

    Altindag, Abdurrahman; Ozkan, Mustafa; Oto, Remzi

    2005-01-01

    The southeastern part of Turkey has comparatively high female suicide rates. We aimed to research social, economic, cultural, and psychiatric reasons of suicides in Batman in a case-controlled psychological autopsy study comparing suicides with matched community controls. The female suicide rate was 9.3 per 100.000 and the female/male ratio was…

  5. Attentional bias toward suicide-related stimuli predicts suicidal behavior.

    OpenAIRE

    Cha, Christine; Najmi, Sadia; Park, Jennifer; Finn, Christine; Nock, Matthew K.

    2010-01-01

    A long-standing challenge for scientific and clinical work on suicidal behavior is that people often are motivated to deny or conceal suicidal thoughts. We proposed that people considering suicide would possess an objectively measurable attentional bias toward suicide-related stimuli, and that this bias would predict future suicidal behavior. Participants were 124 adults presenting to a psychiatric emergency department who were administered a modified emotional Stroop task and followed for si...

  6. Suicide and multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Stenager, Egon; Koch-Henriksen, Nils

    1992-01-01

    In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...... with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age......, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males...

  7. Suicide and forced marriage.

    Science.gov (United States)

    Pridmore, Saxby; Walter, Garry

    2013-03-01

    The prevailing view that the vast majority of those who complete suicide have an underlying psychiatric disorder has been recently challenged by research on the contribution of "predicaments", in the absence of mental illness, to suicide. In this paper, we sought data to support the notion that forced marriage may lead to suicide without the presence of psychiatric disorder. Historical records, newspapers, and the electronic media were searched for examples. Two examples from ancient times and six from the last hundred years were located and described. These cases suggest that forced marriage may lead to suicide and complements earlier findings that loss of fortune, health, liberty, and reputation may lead to suicide in the absence of mental disorder.

  8. Sensitized photo-oxidation of thymidine by 2-methyl-1, 4-naphthoquinone. Characterization of the stable photoproducts

    International Nuclear Information System (INIS)

    Decarroz, C.; Cadet, J.; Murali Krishna, C.; Riesz, P.

    1986-01-01

    The near ultraviolet photolysis of an aerated aqueous solution of thymidine containing 2-methyl-1,4-naphthoquinone gives rise to two main classes of photoproducts as a result of the initial formation of a pyrimidine radical cation. These photo-oxidation products have been separated by high-performance liquid chromatography and further characterized by various spectroscopic techniques including fast atom bombardment mass spectrometry and high field 1 H and 13 C nuclear magnetic resonance analysis. This photoreaction constitutes an excellent model to study the chemical properties of the thymidine radical cation which is expected to be one of the primary consequences of the direct effects of ionizing radiation. (author)

  9. Thymine utilization in Escherichia coli K12. On the role of deoxyribose 1-phosphate and thymidine phosphorylase

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank; Leer, Johan Christian; Nygaard, Per

    1973-01-01

    Exogenously supplied thymine is only poorly utilized by wild-type cells of Escherichia coli for the synthesis of their DNA. It appears that the lack of incorporation of exogenous thymine is due to a lack of endogenous deoxyribosyl groups, which are required for the synthesis of thymidine. Data...... to be presented in this paper indicate that the ability of different thymine auxotrophs to grow on progressively lower thymine concentrations is a function of their capacity to increase the internal pool of deoxyribose 1-phosphate and/or the level of thymidine phosphorylase. Thymine incorporation in wild...

  10. Incorporation of 3H-thymidine during early developmental stages of ovoviviparous and oviparous embryos in the brine

    International Nuclear Information System (INIS)

    Iwasaki, Tamiko

    1980-01-01

    DNA synthesis in the embryos during various developmental stages in the brood pouch of the Artemia female as well as the encysted eggs produced by oviparity was studied by autoradiography using 3 H-thymidine. Nuclei of the embryos through the blastula stage in the brood pouch were labelled, regardless of the existence of the thick shell surrounding the embryos. However, incorporation of 3 H-thymidine into nuclei was absent in the stages between gastrula and early nauplii which had developed in the brood pouch or were delivered from encysted dry eggs. (author)

  11. Gabapentin and suicide attempts.

    Science.gov (United States)

    Gibbons, Robert D; Hur, Kwan; Brown, C Hendricks; Mann, J John

    2010-12-01

    On 16 December 2008, FDA issued a class warning for antiepileptic drugs and suicidal thoughts and behavior. The purpose of this study was to determine if the antiepileptic drug gabapentin increases risk of suicide attempt in patients to which it was prescribed for various indications. We conducted a pharmacoepidemiologic study in which suicide attempt rates were compared before and after gabapentin was prescribed. We used the PharMetrics medical claims database to study the relationship between gabapentin and suicide attempts in a cohort of 131,178 patients with a 1-year window of information before and after initial prescription. Patients had diagnoses of epilepsy, pain disorders, bipolar illness, major depressive disorder, schizophrenia, and other psychiatric disorders. Overall, there was no significant difference in suicide attempt rates before (3.48/1000 patient years--PY) versus after (3.45/1000 PY) gabapentin prescription. Pre-prescription suicide attempt rates were five times higher in psychiatric populations compared with non-psychiatric populations leading us to analyze the two groups separately. No drug effect was detected in the non-psychiatric populations. Significant reductions in suicide attempt rates were seen for bipolar disorder (47.85/1000 PY versus 31.46/1000 PY), major depressive disorder (17.30/1000 PY versus 12.66/1000 PY), and other psychiatric disorders (12.84/1000 PY versus 10.14/1000 PY). Person-time analysis revealed an overall significant reduction in suicide attempt rates (2.01/1000 PY on drug versus 2.30/1000 PY off drug). This study finds that gabapentin does not increase risk of suicide attempts in non-psychiatric populations and is associated with a reduction in suicide attempt risk in patients with psychiatric disorders. Copyright © 2010 John Wiley & Sons, Ltd.

  12. Suicide in New Zealand

    Directory of Open Access Journals (Sweden)

    Said Shahtahmasebi

    2005-01-01

    Full Text Available This paper explores and questions some of the notions associated with suicide including mental illness. On average, about two-thirds of suicide cases do not come into contact with mental health services, therefore, we have no objective assessment of their mental status or their life events. One method of improving our objective understanding of suicide would be to use data mining techniques in order to build life event histories on all deaths due to suicide. Although such an exercise would require major funding, partial case histories became publicly available from a coroner's inquest on cases of suicide during a period of three months in Christchurch, New Zealand. The case histories were accompanied by a newspaper article reporting comments from some of the families involved. A straightforward contextual analysis of this information suggests that (i only five cases had contact with mental health services, in two of the cases this was due to a previous suicide attempt and in the other three it was due to drug and alcohol dependency; (ii mental illness as the cause of suicide is fixed in the public mindset, (iii this in turn makes psychological autopsy type studies that seek information from families and friends questionable; (iv proportionally more females attempt, but more men tend to complete suicide; and (v not only is the mental health-suicide relationship tenuous, but suicide also appears to be a process outcome. It is hoped that this will stimulate debate and the collaboration of international experts regardless of their school of thought.

  13. Emotional Impact of a Video-Based Suicide Prevention Program on Suicidal Viewers and Suicide Survivors

    Science.gov (United States)

    Bryan, Craig J.; Dhillon-Davis, Luther E.; Dhillon-Davis, Kieran K.

    2009-01-01

    In light of continuing concerns about iatrogenic effects associated with suicide prevention efforts utilizing video-based media, the impact of emotionally-charged videos on two vulnerable subgroups--suicidal viewers and suicide survivors--was explored. Following participation in routine suicide education as a part of the U.S. Air Force Suicide…

  14. Suicide in Serbia.

    Science.gov (United States)

    Ilic, M; Ilic, I

    2016-03-15

    Suicide remains a significant public health problem worldwide. The aim of this study was to assess the mortality trend of suicide in Serbia for the years 1991-2014. Data on persons who died of suicide and self-inflicted injury (site codes E950-E959 revision 9 and X60-X84 revision 10 of the International Classification of Diseases to classify death, injury and cause of death) were obtained from the Statistical Office of the Republic of Serbia. The age standardized rate was calculated by direct method (per 100,000 persons, using Segi's World population as standard population). Average annual percentage change (AAPC) with the corresponding 95% confidence interval (CI) was computed for trend using the joinpoint regression analysis. Total 33,930 (24,016 men and 9914 women) suicide deaths occurred in Serbia during the observed period, with the average annual age-standardized mortality rate being 12.7 per 100,000 inhabitants (19.5 per 100,000 in men and 6.7 per 100,000 in women). Suicide mortality in all age groups was higher among men than women. In both genders, suicide rates were highest in the oldest age group. Significantly decreased trend in suicide mortality was recorded continuously from 1991 to 2014 (AAPC=-1.9%, 95%CI -2.2 to -1.6). The most frequently used suicide method in both genders was hanging, strangulation or suffocation with 61.2% off all suicides. Changes in mortality rates were significant both for suicide by firearms, air guns and explosives (AAPC=-1.5% (AAPC=-1.5% in men and -3.1%-3.1% in women) and for suicide by hanging, strangulation, and suffocation (AAPC=-1.2% (AAPC=-1.2% in men and -3.0%-3.0% in women). In men, nonsignificant increase in suicide by firearms, air guns and explosives observed during the period 1991-1997 (by +6.1% per year) was followed by a significant decrease until 2014 (by -3.1% per year). The significantly increased mortality in suicide by firearms, air guns, and explosives was observed in older men (aged 40-69 years and 80

  15. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  16. Characteristics of suicidality among adolescents.

    Science.gov (United States)

    Wetzler, S; Asnis, G M; Hyman, R B; Virtue, C; Zimmerman, J; Rathus, J H

    1996-01-01

    The identification of high-risk adolescent suicide attempters in a population of depressed and suicidal adolescents is of crucial importance. This retrospective study examined characteristics of suicidality (recent and lifetime, active and passive) and psychopathology (depression, aggression, impulsivity, stressful life events, SCL-90 dimensions) among four groups of depressed adolescent outpatients: (1) suicide attempters who required medical treatment (n = 84), (2) suicide attempters who did not require medical treatment (n = 57), (3) suicidal ideators who had never made a suicide attempt (n = 40), and (4) nonsuicidal patients (n = 44). Results indicate that the nonsuicidal group could be differentiated from the three suicidal groups on the basis of suicidality and psychopathology, and that the three suicidal groups could be differentiated from one another on the basis of suicidality but not psychopathology. These findings are discussed in terms of the usefulness of certain self-report measures of suicidality for identifying suicidal adolescents and for differentiating among them. Furthermore, the findings suggest that psychopathological factors do not determine which suicidal adolescents make a medically dangerous suicide attempt and which do not.

  17. Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model

    International Nuclear Information System (INIS)

    Freytag, Svend O.; Paielli, Dell; Wing, Mark; Rogulski, Ken; Brown, Steve; Kolozsvary, Andy; Seely, John; Barton, Ken; Dragovic, Alek; Kim, Jae Ho

    2002-01-01

    Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10 10 vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. Results: In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall

  18. Suicides and suicide ideation in the Bible: an empirical survey.

    Science.gov (United States)

    Koch, H J

    2005-09-01

    The aim of this review is to summarize all data on suicidal behaviour reported in the Bible and to discuss basic implications for medical ethical positions. All books of the Jerusalem Bible, including the apocrypha accepted in the Catholic canon, were searched for all cases of suicide, attempted suicide and suicidal ideation clearly identifiable as such. The Bible including the apocrypha reports about 10 completed suicides and 11 cases of suicide attempt or ideation. The Bible considers human life as a divine gift but suicide per se is neither condemned nor approved. Those suffering from suicidal thoughts are treated with respect and support is offered. Theological teaching on suicide was influenced for centuries by the biased negative opinion of the early fathers of the church and scholastic savants, but these opinions are not substantiated by a thorough reading of the Bible. Copyright (c) 2005 Blackwell Munksgaard

  19. Prioritizing research to reduce youth suicide and suicidal behavior.

    Science.gov (United States)

    Bridge, Jeffrey A; Horowitz, Lisa M; Fontanella, Cynthia A; Grupp-Phelan, Jackie; Campo, John V

    2014-09-01

    The goal of the National Action Alliance for Suicide Prevention is to reduce suicide and suicide attempts in the U.S. by 40% in the next decade. In this paper, a public health approach is applied to suicide prevention to illustrate how reductions in youth suicide and suicidal behavior might be achieved by prioritizing research in two areas: (1) increasing access to primary care-based behavioral health interventions for depressed youth and (2) improving continuity of care for youth who present to emergency departments after a suicide attempt. Finally, some scientific, clinical, and methodologic breakthroughs needed to achieve rapid, substantial, and sustained reductions in youth suicide and suicidal behavior are discussed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Association of Hormonal Contraception With Suicide Attempts and Suicides

    DEFF Research Database (Denmark)

    Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

    2017-01-01

    OBJECTIVE: The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. METHOD: The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women...... in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt......, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal...

  1. Suicide as social logic.

    Science.gov (United States)

    Kral, M J

    1994-01-01

    Although suicide is not viewed as a mental disorder per se, it is viewed by many if not most clinicians, researchers, and lay people as a real or natural symptom of depression. It is at least most typically seen as the unfortunate, severe, yet logical end result of a chain of negative self-appraisals, negative events, and hopelessness. Extending an approach articulated by the early French sociologist Gabriel Tarde, in this paper I argue that suicide is merely an idea, albeit a very bad one, having more in common with societal beliefs and norms regarding such things as divorce, abortion, sex, politics, consumer behavior, and fashion. I make a sharp contrast between perturbation and lethality, concepts central to Edwin S. Shneidman's theory of suicide. Evidence supportive of suicide as an idea is discussed based on what we are learning from the study of history and culture, and about contagion/cluster phenomena, media/communication, and choice of method. It is suggested that certain individuals are more vulnerable to incorporate the idea and act of suicide into their concepts of self, based on the same principles by which ideas are spread throughout society. Just as suicide impacts on society, so does society impact on suicide.

  2. Suicide research before Durkheim.

    Science.gov (United States)

    Goldney, Robert D; Schioldann, Johan A; Dunn, Kirsten I

    2008-01-01

    The casual reader could be forgiven for assuming that there had been little systematic research on suicide before the work of the French sociologist, Emile Durkheim, published in 1897. This historical review demonstrates that there had been extensive studies in the preceding centuries, addressing not only the importance of social factors, but also those factors which are now subsumed in the medical model. In fact, some earlier reviews can now be seen as more balanced and comprehensive than that of Durkheim. In the twentieth century. the predominant focus of suicide research was on the importance of psychosocial factors, a focus which was undoubtedly a legacy of the influential work of Durkheim. Indeed, in 1971 Alvin Alvarez stated that the study of suicide had become the subject of intensive scientific research. The change began in 1897 with the publication of Emile Durkheim's classic Suicide: A Study in Sociology, and more recently Alexander Murray noted that, if the study of suicide had its own era it would divide into two ages, before and after that book ... Le Suicide ... which, more than any other, established its subject as a specialization. Therefore it is not unexpected that many believe that there had not been any substantial suicide research before Durkheim, let alone any which had addressed illness and biological factors and their inter-relationship with society.

  3. Delusions and suicidality.

    Science.gov (United States)

    Grunebaum, M F; Oquendo, M A; Harkavy-Friedman, J M; Ellis, S P; Li, S; Haas, G L; Malone, K M; Mann, J J

    2001-05-01

    Delusions have been considered a risk factor for suicidal behavior. To determine whether specific delusion types are related to suicidal behaviors, the authors compared the clinical characteristics of patients with mood disorders and schizophrenia who did and did not have a history of suicide attempts. After admission for inpatient or outpatient psychiatric treatment, 429 patients (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a structured clinical interview that generated axis I and II diagnoses. In addition, their psychiatric symptoms, history of suicide attempts, and overall functioning were rated. Data for three diagnostic subgroups (223 patients with major depression, 150 with schizophrenia, and 56 with bipolar disorder) were analyzed separately. Multivariate analyses did not find evidence of a relationship between delusions and history of suicidal ideation or suicide attempts in any of the diagnostic groups. This study did not find evidence that the presence of delusions distinguished persons with or without a history of suicide attempt.

  4. Suicide inside: a systematic review of inpatient suicides.

    Science.gov (United States)

    Bowers, Len; Banda, Tumi; Nijman, Henk

    2010-05-01

    The literature on inpatient suicides was systematically reviewed. English, German, and Dutch articles were identified by means of the electronic databases PsycInfo, Cochrane, Medline, EMBASE psychiatry, CINAHL, and British Nursing Index. In total, 98 articles covering almost 15,000 suicides were reviewed and analyzed. Rates and demographic features connected to suicides varied substantially between articles, suggesting distinct subgroups of patients committing suicide (e.g., depressed vs. schizophrenic patients) with their own suicide determinants and patterns. Early in the admission is clearly a high-risk period for suicide, but risk declines more slowly for patients with schizophrenia. Suicide rates were found to be associated with admission numbers, and as expected, previous suicidal behavior was found to be a robust predictor of future suicide. The methods used for suicide are linked to availability of means. Timing and location of suicides seem to be associated with absence of support, supervision, and the presence of family conflict. Although there is a strong notion that suicides cluster in time, clear statistical evidence for this is lacking. For prevention of suicides, staff need to engage with patients' family problems, and reduce absconding without locking the door. Future research should take into account the heterogeneous subgroups of patients who commit suicide, with case-control studies addressing these separately.

  5. Cultural Aspects of Suicide

    Directory of Open Access Journals (Sweden)

    Hari D. Maharajh

    2005-01-01

    Full Text Available Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

  6. Molecular suicide studies of 125I and 3H disintegration in the DNA of Chinese hamster cells

    International Nuclear Information System (INIS)

    Burki, H.J.; Koch, C.; Wolff, S.

    1978-01-01

    Several recent experiments are discussed which yield some new data to help further understand the dramatic sensitivity of mammalian cells to 125 I induced reproductive death. The authors discuss the effects of halogenated pyrimidines on removing the shoulder of the survival curve after tritium thymidine suicide; the effect of oxygen on 125 I decay effects as a functions of the localization of the decays within the nucleus; and recent data on the induction of chromosome aberrations by 125 I DNA decays in CHO cells stored in the G 1 -stage of the cell cycle. (B.R.H.)

  7. Oxidative stress and suicidal erythrocyte death.

    Science.gov (United States)

    Lang, Florian; Abed, Majed; Lang, Elisabeth; Föller, Michael

    2014-07-01

    Eryptosis, the suicidal erythrocyte death, is characterized by cell shrinkage, membrane blebbing, and phosphatidylserine translocation to the outer membrane leaflet. Phosphatidylserine at the erythrocyte surface binds endothelial CXCL16/SR-PSOX (CXC-Motiv-Chemokin-16/Scavenger-receptor-for-phosphatidylserine-and-oxidized-low-density-lipoprotein) and fosters engulfment of affected erythrocytes by phagocytosing cells. Eryptosis serves to eliminate infected or defective erythrocytes, but excessive eryptosis may lead to anemia and may interfere with microcirculation. Clinical conditions with excessive eryptosis include diabetes, chronic renal failure, hemolytic uremic syndrome, sepsis, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose 6-phosphate dehydrogenase deficiency, glutamate cysteine ligase modulator deficiency, and Wilson's disease. Eryptosis is triggered by a wide variety of xenobiotics and other injuries such as oxidative stress. Signaling of eryptosis includes prostaglandin E₂ formation with subsequent activation of Ca(2+)-permeable cation channels, Ca(2+) entry, activation of Ca(2+)-sensitive K(+) channels, and cell membrane scrambling, as well as phospholipase A2 stimulation with release of platelet-activating factor, sphingomyelinase activation, and ceramide formation. Eryptosis may involve stimulation of caspases and calpain with subsequent degradation of the cytoskeleton. It is regulated by AMP-activated kinase, cGMP-dependent protein kinase, Janus-activated kinase 3, casein kinase 1α, p38 kinase, and p21-activated kinase 2. It is inhibited by erythropoietin, antioxidants, and further small molecules. It remains uncertain for most disorders whether eryptosis is rather beneficial because it precedes and thus prevents hemolysis or whether it is harmful because of induction of anemia and impairment of microcirculation. This will address the significance of eryptosis, further mechanisms underlying eryptosis, and additional

  8. Suicide Methods in Asia: Implications in Suicide Prevention

    Science.gov (United States)

    Wu, Kevin Chien-Chang; Chen, Ying-Yeh; Yip, Paul S. F.

    2012-01-01

    As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries. PMID:22690187

  9. Suicide Methods in Asia: Implications in Suicide Prevention

    Directory of Open Access Journals (Sweden)

    Paul S. F. Yip

    2012-03-01

    Full Text Available As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries.

  10. Suicide on Death Row.

    Science.gov (United States)

    Tartaro, Christine; Lester, David

    2016-11-01

    Despite the level of supervision of inmates on death row, their suicide rate is higher than both the male prison population in the United States and the population of males over the age of 14 in free society. This study presents suicide data for death row inmates from 1978 through 2010. For the years 1978 through 2010, suicide rates on death row were higher than that for the general population of males over the age of 15 and for state prisons for all but 2 years. © 2016 American Academy of Forensic Sciences.

  11. Suicide in the World

    Directory of Open Access Journals (Sweden)

    Peeter Värnik

    2012-03-01

    Full Text Available Introduction: Over the past 20 years the WHO has considerably improved world mortality data. There are still shortcomings but more countries now report data and world-wide estimates are regularly made. Methods: Data about mortality have been retrieved from the WHO world database. Worldwide injury mortality estimates for 2008 as well as trends of the suicide rate from 1950 to 2009 were analysed. Results: Suicides in the world amount to 782 thousand in 2008 according to the WHO estimate, which is 1.4% of total mortality and 15% of injury mortality. The suicide rate for the world as a whole is estimated at 11.6 per 100,000 inhabitants. The male–female rate ratio of suicide is estimated to be highest in the European Region (4.0 and the lowest in the Eastern Mediterranean region (1.1. Among males the highest suicide rate in the 15–29 age group is in the SE Asian region, in the 45–59 age group in European males and for ages above 60 in the Western Pacific region. Females from SE Asia have a remarkably high suicide rate among 15–29-year-olds and from age 45 in the Western Pacific region. The leading country is currently Lithuania, with a suicide rate of 34.1 per 100,000 inhabitants. Also among males the suicide rate is the highest in Lithuania at 61.2. Among females South Korea with 22.1 is at the top of world suicide rates. Conclusions: During the past six decades, according to the WHO Japan, Hungary, and Lithuania have topped the list of world countries by suicide rate, but if the current trends continue South Korea will overtake all others in a few years. The heart of the problem of suicide mortality has shifted from Western Europe to Eastern Europe and now seems to be shifting to Asia. China and India are the biggest contributors to the absolute number of suicides in the world.

  12. Firearms and youth suicide.

    Science.gov (United States)

    Boyd, J H; Mościcki, E K

    1986-01-01

    The firearm suicide rate for persons aged 10 to 24 has increased from 2.3 per 100,000 in 1933 to 5.5 per 100,000 in 1982. Over the same period, the suicide rate for this age group by all methods other than firearms has only risen from 2.5 to 3.3. The most dramatic rise in the firearm suicide rate has occurred primarily since 1970, notably among males aged 15 to 24. During the 1960s and 1970s there was a substantial increase in the number of civilian firearms in the United States. PMID:3752329

  13. A procedure for the preparation of radioactive thymidine labelled with 14C

    International Nuclear Information System (INIS)

    Nejedly, Z.; Skodova, H.; Culik, K.; Filip, J.; Kolina, J.; Skoda, J.

    1990-01-01

    14 C-Labelled thymidine can be prepared by conversion of labelled or unlabelled thymine. The preparation is carried out in the presence of labelled or unlabelled 2-deoxycytidine, of a surfactant and a of reaction stimulator in a buffer at a temperature of 3 to 38 degC, under the catalytic effect of biocatalysts prepared from Escherichia coli B bacterial cells which are immobilized by embedding into an inert carrier. Sodium dodecyl sulfate can serve as the surfactant, D-glucose as the reaction-stimulating substrate, and sodium alginate as the inert cell carrier. In the procedure suggested, catalytic properties of enzymes are utilized without the need to isolate the enzymes from the bacterial cells beforehand or to purify them. The bacterial cells can be applied repeatedly in several production batches and stored in physiological solution at 5 degC. (M.D.)

  14. Tritiated thymidine radiotoxicity in mice embryos in preimplantation phase, culture and in vitro fertilization

    International Nuclear Information System (INIS)

    Kikuchi, O.K.; Ohyama, H.; Yamamada, T.

    1992-01-01

    Mouse embryos have been used as a good biological system to study the effects of ionizing radiation on proliferating cells and on the mammal embryos development. In vitro fertilization is an ideal technique for irradiating or labelling many zygotes at the same developmental stage and with the the same developmental stage and with the security that it will not have any influence of maternal organism. In the present work different concentrations of methyl- 3 H-thymidine was added to the culture medium micro drops containing the zygotes at pro nuclear stage and the embryos were cultured in vitro at 37 0 C in a humidified atmosphere with 5% of CO 2 for four days up established end point to calculate the LD 50 , the 50% lethal dose. (author)

  15. Bacterial incorporation of tritiated thymidine and populations of bacteriophagous fauna in the rhizosphere of wheat

    DEFF Research Database (Denmark)

    Christensen, Henrik; Griffiths, Bryan; Christensen, Søren

    1992-01-01

    Bacterial and microfaunal populations, and bacterial productivity measured by tritiated thymidine (3HTdr) incorporation, in the rhizosphere of wheat seedlings were measured. Soil from planted pots was fractionated into rhizosphere and non-rhizosphere (bulk) soil, while unplanted soil was taken from...... pots without plants. Total bacterial counts and biovolume did not differ between fractions but viable (plate) counts were 8 times higher in the rhizosphere compared to bulk and unplanted soil. 3HTdr was incorporated at a constant rate with low variability in bulk or unplanted soil. In rhizosphere soil...... 3HTdr incorporation was lower than in bulk or unplanted soils and showed high variability. The populations of bacterial-feeding protozoa and nematodes indicated that rhizosphere bacterial activity was actually 3–4 times greater in rhizosphere than bulk soil in accordance with the results...

  16. Cytoenzymology and 3H-thymidine uptake of retro-ocular connective tissue cultures in experimental endocrino-exophthalmos.

    Science.gov (United States)

    Vaida, E; Petrescu, R; Ghinea, E; Stefaneanu, L

    1976-01-01

    The in vitro retro-ocular connective tissue cultures from guinea pigs with endocrine exophthalmos were studied before and after retro-ocular treatment with cortisol and hyaluronidase. Both cortisol and hyaluronidase inhibited the cell proliferation, the cytoenzymic activities of oxydoreductases, the 3H-thymidine uptake, the number of mitoses and the protein content of cultivated cells.

  17. Syntheses of N3-substituted thymine acyclic nucleoside phosphonates and a comparison of their inhibitory effect towards thymidine phosphorylase

    Czech Academy of Sciences Publication Activity Database

    Pomeisl, Karel; Holý, Antonín; Votruba, Ivan; Pohl, Radek

    2008-01-01

    Roč. 18, č. 4 (2008), s. 1364-1367 ISSN 0960-894X Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * thymidine phosphorylase * fluorination * pyrimidine Subject RIV: CC - Organic Chemistry Impact factor: 2.531, year: 2008

  18. Perturbation of DNA replication and cell cycle progression by commonly used ( sup 3 H)thymidine labeling protocols

    Energy Technology Data Exchange (ETDEWEB)

    Hoy, C.A.; Lewis, E.D.; Schimke, R.T. (Stanford Univ., CA (USA))

    1990-04-01

    The effect of tritiated thymidine incorporation on DNA replication was studied in Chinese hamster ovary cells. Rapidly eluting (small) DNA from cells labeled with 2 microCi of ({sup 3}H)thymidine per ml (200 microCi/mmol) for 60 min matured to a large nonelutable size within approximately 2 to 4 h, as measured by the alkaline elution technique. However, DNA from cells exposed to 10 microCi of ({sup 3}H)thymidine per ml (66 microCi/mmol) was more rapidly eluting initially and did not mature to a nonelutable size during subsequent incubation. Semiconservative DNA replication measured by cesium chloride gradient analysis of bromodeoxyuridine-substituted DNA was also found to be affected by the final specific activity of the ({sup 3}H)thymidine used in the labeling protocol. Dramatic cell cycle perturbations accompanied these effects on DNA replication, suggesting that labeling protocols commonly used to study DNA metabolism produce aberrant DNA replication and subsequent cell cycle perturbations.

  19. Short-term variability in bacterial abundance, cell properties, and incorporation of leucine and thymidine in subarctic sea ice

    DEFF Research Database (Denmark)

    Kaartokallio, H.; Søgaard, D.H.; Norman, L.

    2013-01-01

    Sea ice is a biome of immense size and provides a range of habitats for diverse microbial communities, many of which are adapted to living at low temperatures and high salinities in brines. We measured simultaneous incorporation of thymidine (TdR) and leucine (Leu), bacterial cell abundance...

  20. Acycloguanosyl 5'-thymidyltriphosphate, a thymidine analogue prodrug activated by telomerase, reduces pancreatic tumor growth in mice.

    Science.gov (United States)

    Polvani, Simone; Calamante, Massimo; Foresta, Valeria; Ceni, Elisabetta; Mordini, Alessandro; Quattrone, Alessandro; D'Amico, Massimo; Luchinat, Claudio; Bertini, Ivano; Galli, Andrea

    2011-02-01

    Gemcitabine is the standard of care for metastatic and nonresectable pancreatic tumors. Phase II and III trials have not demonstrated efficacy of recently developed reagents, compared with gemcitabine alone; new chemotherapic agents are needed. Ninety percent of pancreatic tumors have telomerase activity, and expression correlates with tumor stage. We developed a thymidine analogue prodrug, acycloguanosyl 5'-thymidyltriphosphate (ACV-TP-T), that is metabolized by telomerase and releases the active form of acyclovir. We investigated the antitumor efficacy of ACV-TP-T in vitro and in vivo. We evaluated proliferation and apoptosis of human pancreatic cancer cells (PANC-1, MiaPaca2, BxPc3, PL45, and Su.86.86) incubated with ACV-TP-T. The presence of ACV-TP-T and its metabolite inside the cells were analyzed by mass spectrometry. In vivo efficacy was evaluated in nude mice carrying PANC-1 or MiaPaca2 pancreatic xenograft tumors. The prodrug of ACV-TP-T was actively metabolized inside pancreatic cancer cells into the activated form of acyclovir; proliferation was reduced, apoptosis was increased, and the cell cycle was altered in pancreatic cancer incubated with ACV-TP-T, compared with controls. Administration of ACV-TP-T to mice reduced growth, increased apoptosis, and reduced proliferation and vascularization of pancreatic xenograft tumors. ACV-TP-T, a thymidine analogue that is metabolized by telomerase and releases the active form of acyclovir, reduces proliferation and induces apoptosis of human pancreatic cancer cell lines in vitro and pancreatic xenograft tumors in mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Cognitive Distortions and Suicide Attempts.

    Science.gov (United States)

    Jager-Hyman, Shari; Cunningham, Amy; Wenzel, Amy; Mattei, Stephanie; Brown, Gregory K; Beck, Aaron T

    2014-08-01

    Although theorists have posited that suicidal individuals are more likely than non-suicidal individuals to experience cognitive distortions, little empirical work has examined whether those who recently attempted suicide are more likely to engage in cognitive distortions than those who have not recently attempted suicide. In the present study, 111 participants who attempted suicide in the 30 days prior to participation and 57 psychiatric control participants completed measures of cognitive distortions, depression, and hopelessness. Findings support the hypothesis that individuals who recently attempted suicide are more likely than psychiatric controls to experience cognitive distortions, even when controlling for depression and hopelessness. Fortune telling was the only cognitive distortion uniquely associated with suicide attempt status. However, fortune telling was no longer significantly associated with suicide attempt status when controlling for hopelessness. Findings underscore the importance of directly targeting cognitive distortions when treating individuals at risk for suicide.

  2. Association of Hormonal Contraception With Suicide Attempts and Suicides.

    Science.gov (United States)

    Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel; Lange, Theis; Lidegaard, Øjvind

    2018-04-01

    The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception. Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85-2.10) for suicide attempt and 3.08 (95% CI=1.34-7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79-2.03) for oral combined products, 2.29 (95% CI=1.77-2.95) for oral progestin-only products, 2.58 (95% CI=2.06-3.22) for vaginal ring, and 3.28 (95% CI=2.08-5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use. Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.

  3. Chechen Female Suicide Terrorism

    Science.gov (United States)

    2017-06-01

    Making Death Visible: Chechen Female Suicide Bombers in an Era of Globalization (ProQuest, 2009), 65. 91 Gammer, “Nationalism and History ,” 121. 92...18 III. CASE STUDY: THE RUSSO–CHECHEN CONFLICT .................................19 A. CHECHEN HISTORY ...Bloom, “Female Suicide Bombers: A Global Trend,” Daedalus, 136, no. 1 (2007): 94. 2 Mia Bloom, Bombshell (Philadelphia: University of Pennsylvania

  4. HOMICIDE FOLLOWED BY SUICIDE

    OpenAIRE

    SAMANTHA DUBUGRAS; BLANCA SUSANA GUEVARA WERLANG

    2007-01-01

    Homicide followed by suicide (H/S) is a complex and poorly studied phenomenon. This research aims at identifyingH/S cases occurred in Porto Alegre from 1996 throughout 2004. Information on H/S was extracted from newspapers,police reports and interviews with the informants. From the 14 identified cases, men were the killers/suicides andwomen and children their victims. The most frequently used weapons were firearms. In general, the aggressor was animpulsive, aggressive individual showing probl...

  5. Neurobiology of Elderly Suicide.

    Science.gov (United States)

    Richard-Devantoy, S; Turecki, G; Jollant, F

    2016-07-02

    Suicide in the elderly is an underestimated and complex issue that has mainly been explored in sociological, clinical and psychological perspectives. Suicide in non-elderly adults has been associated with diverse neurobiological alterations that may shed light on future predictive markers and more efficient preventative interventions. The aim of this paper was to review studies specifically investigating the neurobiology of elderly suicidal behaviour. We performed a systematic English and French Medline and EMBASE search until 2013. Contrary to literature about the non-elderly, we found a paucity of studies investigating the biomarkers of suicidal risk in elderly adults. Main findings were found in the neurocognitive domain. Studies generally supported the existence of cognitive deficits, notably decision-making impairment and reduced cognitive inhibition, in patients with a history of suicidal act compared to patients without such history. However, replications are needed to confirm findings. Due to several limitations including the small number of available studies, frequent lack of replication and small sample size, no firm conclusions can be drawn. The authors encourage further investigations in this field as insight in the neurobiology of these complex behaviors may limit clichés about end of life and aging, as well as improve future prevention of suicide in the elderly.

  6. Suicide and crisis management

    Directory of Open Access Journals (Sweden)

    B S Chavan

    2015-01-01

    Full Text Available Suicide among the general population is a major public health problem and thus is a cause of concern for India. Since suicide is the outcome of multiple factors including socioeconomic, cultural, religious, and political; intervention and prevention strategies will vary from region to region. The legal framework and guidelines in a country can influence the suicide rate by eliminating barriers to mental health services, by adopting and strictly implementing policies on access to firearms for persons with risk of suicide, providing services for treatment of substance abuse patients, and by training of school personnel so that they can identify and assist vulnerable youth in accessing help. Mental Healthcare Bill (MHCB, 2013, will soon become the guiding law for the treatment and rehabilitation of persons suffering from mental health issues. Although MHCB has been criticized on many fronts, it still has laudable provisions that attempt to address reducing treatment gap through the proposal of availability of minimum mental health facilities at primary health center, proposing comprehensive treatment facilities including rehabilitation and the proposal to remove attempted suicide from Section 309 of IPS, etc., which might contribute in suicide prevention and other mental health crisis situations.

  7. Modeling suicide in bipolar disorders.

    Science.gov (United States)

    Malhi, Gin S; Outhred, Tim; Das, Pritha; Morris, Grace; Hamilton, Amber; Mannie, Zola

    2018-02-19

    Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only

  8. Suicide in ancient Greece.

    Science.gov (United States)

    Laios, K; Tsoukalas, G; Kontaxaki, M-I; Karamanou, M; Androutsos, G

    2014-01-01

    The theme of suicide appears several times in ancient Greek literature. However, each such reference acquires special significance depending on the field from which it originates. Most of the information found in mythology, but the suicide in a mythological tale, although in terms of motivation and mental situation of heroes may be in imitation of similar incidents of real life, in fact is linked with the principles of the ancient Greek religion. In ancient drama and mainly in tragedies suicide conduces to the tragic hypostasis of the heroes and to the evolution of the plot and also is a tool in order to be presented the ideas of poets for the relations of the gods, the relation among gods and men and the relation among the men. In ancient Greek philosophy there were the deniers of suicide, who were more concerned about the impact of suicide on society and also these who accepted it, recognizing the right of the individual to put an end to his life, in order to avoid personal misfortunes. Real suicides will be found mostly from historical sources, but most of them concern leading figures of the ancient world. Closer to the problem of suicide in the everyday life of antiquity are ancient Greek medicines, who studied the phenomenon more general without references to specific incidents. Doctors did not approve in principal the suicide and dealt with it as insane behavior in the development of the mental diseases, of melancholia and mania. They considered that the discrepancy of humors in the organ of logic in the human body will cause malfunction, which will lead to the absurdity and consequently to suicide, either due to excessive concentration of black bile in melancholia or due to yellow bile in mania. They believed that greater risk to commit suicide had women, young people and the elderly. As therapy they used the drugs of their time with the intention to induce calm and repression in the ill person, therefore they mainly used mandragora. In general, we would say

  9. Googling suicide: surfing for suicide information on the Internet.

    Science.gov (United States)

    Recupero, Patricia R; Harms, Samara E; Noble, Jeffrey M

    2008-06-01

    This study examined the types of resources a suicidal person might find through search engines on the Internet. We were especially interested in determining the accessibility of potentially harmful resources, such as prosuicide forums, as such resources have been implicated in completed suicides and are known to exist on the Web. Using 5 popular search engines (Google, Yahoo!, Ask.com, Lycos, and Dogpile) and 4 suicide-related search terms (suicide, how to commit suicide, suicide methods, and how to kill yourself), we collected quantitative and qualitative data about the search results. The searches were conducted in August and September 2006. Several coraters assigned codes and characterizations to the first 30 Web sites per search term combination (and "sponsored links" on those pages), which were then confirmed by consensus ratings. Search results were classified as being prosuicide, antisuicide, suicide-neutral, not a suicide site, or error (i.e., page would not load). Additional information was collected to further characterize the nature of the information on these Web sites. Suicide-neutral and anti-suicide pages occurred most frequently (of 373 unique Web pages, 115 were coded as suicide-neutral, and 109 were anti-suicide). While pro-suicide resources were less frequent (41 Web pages), they were nonetheless easily accessible. Detailed how-to instructions for unusual and lethal suicide methods were likewise easily located through the searches. Mental health professionals should ask patients about their Internet use. Depressed, suicidal, or potentially suicidal patients who use the Internet may be especially at risk. Clinicians may wish to assist patients in locating helpful, supportive resources online so that patients' Internet use may be more therapeutic than harmful.

  10. Homicide Followed by Suicide: A Comparison with Homicide and Suicide

    Science.gov (United States)

    Liem, Marieke; Nieuwbeerta, Paul

    2010-01-01

    Homicide-suicides are a rare yet very serious form of lethal violence which mainly occurs in partnerships and families. The extent to which homicide-suicide can be understood as being primarily a homicide or a suicide event, or rather a category of its own is examined. In total, 103 homicide-suicides were compared to 3,203 homicides and 17,751…

  11. DST non-suppression predicts suicide after attempted suicide.

    Science.gov (United States)

    Jokinen, Jussi; Carlborg, Andreas; Mårtensson, Björn; Forslund, Kaj; Nordström, Anna-Lena; Nordström, Peter

    2007-04-15

    Most prospective studies of HPA axis have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during the follow-up. Attempted suicide is a strong clinical predictor of suicide. The aim of this study was to assess the predictive value of DST for suicide in a group of depressed inpatients with and without an index suicide attempt. Historical cohort of 382 psychiatric inpatients with mood disorder admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000 were submitted to the DST and followed up for causes of death. During the follow-up (mean 18 years), 36 suicides (9.4%) occurred, 20 of these were non-suppressors and 16 were suppressors. There was no statistically significant difference in suicide risk between the suppressors and non-suppressors for the sample as a whole. An index suicide attempt predicted suicide. In suicide attempters with mood disorder, the non-suppressor status was significantly associated with suicide indicating that HPA axis hyperactivity is a risk factor for suicide in this group. The dexamethasone suppression test may be a useful predictor within this population.

  12. Firearms and suicide in Australia.

    Science.gov (United States)

    Cantor, C H; Lewin, T

    1990-12-01

    Australia has a moderate overall suicide rate but an extremely high male firearm suicide rate. Using data covering the years 1961-1985, a series of multiple regression based analyses were performed. During this period, overall suicide rates fell but firearm suicides remained constant with a resulting increase in the proportion of suicides by firearms. There has been an increase in suicides in the young offset by a decline in the elderly. Young males showed the greatest proportional increase in the use of firearms. A limited regional analysis supported the hypothesis that lack of legislative restrictions on long guns in Queensland with a greater household prevalence of such weapons and different cultural attitudes were associated with higher overall and firearm suicide rates. Such findings are consistent with reports from North America, although trends in Australia are more modest. Reducing the availability and cultural acceptance of firearms is likely to decrease suicide rates, especially in males.

  13. About Teen Suicide (For Parents)

    Science.gov (United States)

    ... Feelings Expert Answers Q&A Movies & More for Teens Teens site Sitio para adolescentes Body Mind Sexual ... Safe Videos for Educators Search English Español About Teen Suicide KidsHealth / For Parents / About Teen Suicide What's ...

  14. End of Life: Suicide Grief

    Science.gov (United States)

    Healthy Lifestyle End of life A loved one's suicide can be emotionally devastating. Use healthy coping strategies — ... Clinic Staff When a loved one dies by suicide, overwhelming emotions can leave you reeling. Your grief ...

  15. Train suicides in The Netherlands

    NARCIS (Netherlands)

    van Houwelingen, Cornelis A. J.; Kerkhof, Ad J. F. M.; Beersma, Domien G. M.

    2010-01-01

    Background: Little is known about train suicide and factors influencing its prevalence. This study tests the hypotheses that railway density, railway transportation volume, familiarity with railway transportation and population density contribute to train suicide. It also tests the relationship

  16. [Suicide in Spain today].

    Science.gov (United States)

    Ruiz-Pérez, Isabel; Olry de Labry-Lima, Antonio

    2006-03-01

    Spain presents one of the lowest suicide rates (8.7 per 100,000) but, as well as Ireland, it has also experienced one of the highest rate increases both within Europe and within the world. In our country, it can be observed an increase in the suicide rates from 1975 to 1994, being this increase greater in men than in women. It can also be noted that there was a stabilisation in the following years. Social factors, specially those which have to deal with gender roles and changes in these roles, are the most common explanations. Another possible explanation for the observed increase in mortality due to suicide among young men could be the AIDS epidemic and intravenous drug addiction, that was observed in Spain during the eighties and nineties. Furthermore, we are witnessing an epidemic related to violence against children and women. Literature strongly suggests that child abuse (psychological and sexual) is associated with increased suicide risk in adolescent or adult life. Women experience violence from their intimate partners and have a greater risk of suffering from chronic pain, diverse somatisations, greater substance use like drugs and alcohol, depression and suicide attempt. The association between work precariousness and suicide seems to be due to economic and social and family support factors, which can lead to greater vulnerability to mental health problems. These factors are of great relevance, since Spain presents one of the highest unemployment and temporary employment rates in the European Union. It seems reasonable that, due to the individualism that characterises the contemporary society, its demands and the new role of women in the work market that cause, among others, a greater difficulty in combining work and family life, are factors that could explain the lack of decrease in suicide rates.

  17. Suicidal Behavior in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Bedriye Oncu

    2013-03-01

    Full Text Available Suicide associated mortality rates are notable for eating disorders. Crude mortality rate associated with suicide, varies between 0% and 5.3% in patients with eating disorders. Prominent risk factors for suicidal behavior among these patients are subtype of the eating disorders, comorbid psychiatric diagnosis (e.g. depression, alcohol and substance abuse, personality disorders, ultrarapid drug metabolism, history of childhood abuse and particular family dynamics. In this article, suicidal behavior and associated factors in eating disorders are briefly reviewed.

  18. Train suicides in The Netherlands.

    Science.gov (United States)

    van Houwelingen, Cornelis A J; Kerkhof, Ad J F M; Beersma, Domien G M

    2010-12-01

    Little is known about train suicide and factors influencing its prevalence. This study tests the hypotheses that railway density, railway transportation volume, familiarity with railway transportation and population density contribute to train suicide. It also tests the relationship between train suicide and general population suicide and examines the prevalence and the characteristics of high-risk locations and their contribution to the grand total of train suicides. Trends in train suicides were compared with trends in railway track length, train kilometres, passenger kilometres and national suicide figures over the period 1950-2007. The geographical distribution over the national network over the period 1980-2007 was studied. Data were obtained from The Netherlands Railways, Prorail and Statistics Netherlands. 1. The incidence of train suicides is unrelated to railway parameters. 2. Being familiar with railway transportation as a passenger is not a contributory factor. 3. Train suicide rates are unrelated to regional population density. 4. The incidence of train suicides parallels that of general population suicides. 5. Half of the train suicides took place at a limited number of locations, the most important of which were situated within a village or town and were close to a psychiatric hospital. Most conclusions are based on correlational relationships between variables. 1. Train suicide trends reflect trends in general population suicides. 2. Increased train transportation does not lead to more train suicides. 3. The prevention of train suicide at high-risk locations (HRLs) in built-up areas and near psychiatric hospitals deserves first priority. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Suicidal Behavior among Latino Youth.

    Science.gov (United States)

    Canino, Glorisa; Roberts, Robert E.

    2001-01-01

    Reviews the scientific literature related to suicidal behavior among Latino youth. Discusses the conceptualizations of culture, and how culture may influence behavior and psychopathology, in particular, suicidal behavior. Reviews the literature that discusses rates of suicidal behavior, risk, and protective factors associated with this behavior…

  20. Suicide Prevention for LGBT Students

    Science.gov (United States)

    Johnson, R. Bradley; Oxendine, Symphony; Taub, Deborah J.; Robertson, Jason

    2013-01-01

    Extensive media coverage of the suicide deaths of several gay and lesbian youth has highlighted lesbian, gay, bisexual, and transgender (LGBT) youth as a population at-risk for suicide. In addition, it has caused colleges and universities to address mental health and suicide behavior among this very diverse college population. One issue that…

  1. Your Role in Suicide Prevention.

    Science.gov (United States)

    Pollard, Robert

    1986-01-01

    Information to help teachers recognize the potential for suicide among hearing impaired and other students is presented. The "Suicide Decision Tree" emphasizes six important content areas (verbal signs, behavioral signs, stressors, past history, suicide plan, and resources) throughout a three-part process of monitoring, investigating, and…

  2. Suicide Prevention: does it work?

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    2016-03-05

    Mar 5, 2016 ... suicide, family violence (including physical or sexual abuse), having guns or other firearms in the home, incarceration and exposure to others' suicidal behavior (such as that of family members, peers, or media figures). Research suggests that people who attempt suicide differ from others in many aspects of ...

  3. The Ethics of Assisted Suicide.

    Science.gov (United States)

    Callahan, Jay

    1994-01-01

    From social work perspective, considers ethics of assisted suicide. Discusses traditional social work value of client self-determination and identifies tensions in this ideal and conflicts with value of client well-being. Finds assisted suicide unethical, arguing that studies have shown judgment of most suicidal people to be impaired as result of…

  4. Teenage Suicide: A Critical Issue.

    Science.gov (United States)

    NJEA Review, 1982

    1982-01-01

    Suicide and attempted suicide among teenagers has risen dramatically since 1960, especially among girls. Three theories of the causes of suicide (emotional crises, brain chemistry and nonexpression of grief) are discussed. Depression and other first stage warning signals, and the nature of second stage "cries for help," are considered. (CM)

  5. Mysore study: A study of suicide notes

    OpenAIRE

    Namratha, P.; Kishor, M.; Sathyanarayana Rao, T. S.; Raman, Rajesh

    2015-01-01

    Background: Suicide is one of the leading causes of preventable deaths. Recent data suggest South India as one of the regions with highest suicide rates in the world. In 2013, 134,799 people committed suicide in India according to the statistics released by the National Crime Records Bureau. Suicide note is one of the most important sources to understand suicide, which may be beneficial in suicide prevention. Studies on suicidal notes from this part of the world are sparse. Objective: The aim...

  6. Police and Suicide Prevention.

    Science.gov (United States)

    Marzano, Lisa; Smith, Mark; Long, Matthew; Kisby, Charlotte; Hawton, Keith

    2016-05-01

    Police officers are frequently the first responders to individuals in crisis, but generally receive little training for this role. We developed and evaluated training in suicide awareness and prevention for frontline rail police in the UK. To investigate the impact of training on officers' suicide prevention attitudes, confidence, and knowledge. Fifty-three participants completed a brief questionnaire before and after undertaking training. In addition, two focus groups were conducted with 10 officers to explore in greater depth their views and experiences of the training program and the perceived impact on practice. Baseline levels of suicide prevention attitudes, confidence, and knowledge were mixed but mostly positive and improved significantly after training. Such improvements were seemingly maintained over time, but there was insufficient power to test this statistically. Feedback on the course was generally excellent, notwithstanding some criticisms and suggestions for improvement. Training in suicide prevention appears to have been well received and to have had a beneficial impact on officers' attitudes, confidence, and knowledge. Further research is needed to assess its longer-term effects on police attitudes, skills, and interactions with suicidal individuals, and to establish its relative effectiveness in the context of multilevel interventions.

  7. [Family, Suicide and Mourning].

    Science.gov (United States)

    Garciandía Imaz, José Antonio

    2013-01-01

    Death is an event that always breaks into family life in a surprising way. Of all the deaths, suicide is the one which more strongly questions the functionality of a family and increases the risk of difficulties in the mourning process. Families in which a suicide has occurred are exposed to a greater possibility of disintegration, disorganization and pathological expressions in their members. To present a reduced and circumscribed narrative revision, restricted to examine the relationship between suicide and the mourning process in the family. The suicide of a loved one is an event that may contribute to pathological grief and mental dysfunctions in surviving relatives. Death in the family is a natural phenomenon. However, death by suicide is one of the phenomena that can generate more alterations in the structure and organization of the family, due to the difficulty related to the mourning process. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  8. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Risk of repetition of suicide attempt, suicide or all deaths after an episode of attempted suicide

    DEFF Research Database (Denmark)

    Christiansen, Erik; Jensen, Børge Frank

    2007-01-01

    This study was undertaken in order to estimate the incidence of repetition of suicide attempt, suicide and all deaths, and to analyse the influence of psychiatric illness and socio-demographic factors on these.......This study was undertaken in order to estimate the incidence of repetition of suicide attempt, suicide and all deaths, and to analyse the influence of psychiatric illness and socio-demographic factors on these....

  10. Suicide and mental illness in parents and risk of suicide in offspring

    DEFF Research Database (Denmark)

    Sørensen, Holger Jelling; Mortensen, Erik Lykke; Wang, August Gabriel

    2009-01-01

    A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide.......A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide....

  11. Gaps in Crisis Mental Health: Suicide and Homicide-Suicide.

    Science.gov (United States)

    Carretta, Carrie M; Burgess, Ann W; Welner, Michael

    2015-10-01

    Gaps in crises of mental health emerge from poor distinction between the qualities of people who suicide and those who murder and then kill themselves. The role, if any, that substance use has in such lethal violence is an example of such a lack of distinction. In this study, a sample of medical examiner investigative and toxicology reports from Los Angeles and Orange counties in California were available for analysis for 432 suicide cases and 193 homicide-suicide cases. This informed clearer toxicological and pharmacological distinction of suicide from homicide-suicide. Blood alcohol levels were higher in persons committing suicide than in homicide-suicide perpetrators (p=.004). Homicide-suicide perpetrators had almost twice the level of stimulants in their system than people who suicide (p=.022) but did not have comparatively elevated levels of drugs or alcohol. Predictors of suicide included the following: substance abuse history, high number of drugs in system, death inside a house, and legal impairment by alcohol. Predictors of homicide-suicide included gunshot as the cause of death, female gender, domestic conflict, children living in the home, and prior arrest for substance abuse. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Effects of suicide bereavement on mental health and suicide risk

    DEFF Research Database (Denmark)

    Pitman, Alexandra; Osborn, David; King, Michael

    2014-01-01

    Between 48 million and 500 million people are thought to experience suicide bereavement every year. Over the past decade, increased policy attention has been directed towards suicide bereavement, but with little evidence to describe the effect of exposure or to provide appropriate responses. We u....... Policymakers should consider how to strengthen health and social care resources for people who have been bereaved by suicide to prevent avoidable mortality and distress....... used a systematic approach to carry out a narrative review of studies of the effect of suicide bereavement on mortality, mental health, and social functioning, and compared them with effects from other bereavements. We found 57 studies that satisfied strict inclusion criteria. Results from...... these studies suggested that exposure to suicide of a close contact is associated with several negative health and social outcomes, depending on an individual's relationship to the deceased. These effects included an increased risk of suicide in partners bereaved by suicide, increased risk of required admission...

  13. Attempted suicide in Denmark. III. Assessment of repeated suicidal behaviour

    DEFF Research Database (Denmark)

    Wang, A G; Nielsen, B; Bille-Brahe, U

    1985-01-01

    Ninety-nine patients, randomly chosen among hospital admitted suicide attempters, were initially interviewed at the Department of Psychiatry, Odense University Hospital, Denmark, and then followed up for a period of about 3 years. Half of the patients repeated the attempt in the follow-up period......, mostly in the first year. Ten patients committed suicide, half of them in the first 3 months after the interview, shortly after discharge from hospital. The majority of the repeaters were living alone, while those that committed suicide were mostly married women aged 50-60 years. Other characteristic...... features for the repeaters were previous suicidal behaviour and suicidal behaviour among relatives. Many had a psychiatric record and expressed chronic somatic complaints. Around the time of the attempt, many expressed hopelessness, isolation and suicidal ideation. Pierce's Suicide Intent Scale performed...

  14. Controlling Access to Suicide Means

    Science.gov (United States)

    Sarchiapone, Marco; Mandelli, Laura; Iosue, Miriam; Andrisano, Costanza; Roy, Alec

    2011-01-01

    Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies. PMID:22408588

  15. Controlling Access to Suicide Means

    Directory of Open Access Journals (Sweden)

    Miriam Iosue

    2011-12-01

    Full Text Available Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs, as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.

  16. Controlling access to suicide means.

    Science.gov (United States)

    Sarchiapone, Marco; Mandelli, Laura; Iosue, Miriam; Andrisano, Costanza; Roy, Alec

    2011-12-01

    Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords "suicide means", "suicide method", "suicide prediction" or "suicide prevention" and other relevant keywords. A number of factors may influence an individual's decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing "safe rooms" in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.

  17. An Integrative Suicide Prevention Program for Visitor Charcoal Burning Suicide and Suicide Pact

    Science.gov (United States)

    Wong, Paul W. C.; Liu, Patricia M. Y.; Chan, Wincy S. C.; Law, Y. W.; Law, Steven C. K.; Fu, King-Wa; Li, Hana S. H.; Tso, M. K.; Beautrais, Annette L.; Yip, Paul S. F.

    2009-01-01

    An integrative suicide prevention program was implemented to tackle an outbreak of visitor charcoal burning suicides in Cheung Chau, an island in Hong Kong, in 2002. This study evaluated the effectiveness of the program. The numbers of visitor suicides reduced from 37 deaths in the 51 months prior to program implementation to 6 deaths in the 42…

  18. N(3)-protection of thymidine with Boc for an easy synthetic access to sugar-alkylated nucleoside analogs.

    Science.gov (United States)

    Simeone, Luca; De Napoli, Lorenzo; Montesarchio, Daniela

    2012-03-01

    The use of Boc as a nucleobase-protecting group in the synthesis of sugar-modified thymidine analogs is reported. Boc was easily inserted at N(3) by a simple and high-yielding reaction and found to be stable to standard treatments for the removal of Ac and (t) BuMe(2) Si (TBDMS) groups, as well as to ZnBr(2) -mediated 4,4'-dimethoxytrityl (DMTr) deprotection. Boc Protection proved to be completely resistant to the strong basic conditions required to regioselectively achieve O-alkylation, therefore, providing synthetic access to a variety of sugar-alkylated nucleoside analogs. To demonstrate the feasibility of this approach, two 3'-O-alkylated thymidine analogs have been synthesized in high overall yields and fully characterized. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  19. Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives

    Science.gov (United States)

    Lettieri, R.; D'Abramo, M.; Stella, L.; La Bella, A.; Leonelli, F.; Giansanti, L.; Venanzi, M.; Gatto, E.

    2018-04-01

    Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

  20. Male depression and suicide.

    Science.gov (United States)

    Wålinder, J; Rutzt, W

    2001-03-01

    Based on the experiences of the Gotland Study that education of general practitioners about depressive illness resulted in a statistically significant reduction in the number of female suicides, leaving the rate of male suicides almost unaffected, we propose the concept of a male depressive syndrome. This syndrome comprises a low stress tolerance, an acting-out behavior, a low impulse control, substance abuse and a hereditary loading of depressive illness, alcoholism and suicide. This notion is supported by data from The Amish study as well as the concept of van Praag of a stress-precipitated, cortisol-induced, serotonin-related and anxiety-driven depressive illness most often seen in males. In order to identify depressed males, the Gotland Male Depression Scale has been developed. Some preliminary data using the scale in a group of alcohol-dependant patients are presented.

  1. Suicide in centenarians

    DEFF Research Database (Denmark)

    Shah, Ajit; Zarate-Escudero, Sofia; Bhat, Ravi

    2014-01-01

    BACKGROUND: The elderly population size is growing worldwide due increased life expectancy and decreased mortality in the elderly. This has lead to an increase in the number of centenarians, and their numbers are predicted to increase further. Little is known about suicide rates in centenarians....... METHODS: Data on the number of suicides (ICD-10 codes, X60-84) in entenarians of both gender for as many years as possible from 2000 were ascertained from three sources: colleagues, national statisics office websites and e-mail contact with the national statistics offices of as many countries as possible....... The number of centernarians for the corresponding years was estimated for each country using data provided by the United Nations website. RESULTS: Data were available from 17 countries. The suicide rate was 57 (95% confidence interval 45-69) per 100, 000 person years in men and 6.8 (95% confidence interval 5...

  2. Dostoevsky and suicide.

    Science.gov (United States)

    Foy, J L; Rojcewicz, S J

    1979-01-01

    Fyodor Dostoevsky has continued to grow in stature and influence among modern writers. His modernity is based, among other things, upon his psychological penetration of character and motive. Suicide received considerable attention and analysis in his novels and stories. Although dynamic psychiatry has always held Dostoevsky in high regard, practically all psychiatrists have tended to ignore Dostoevsky's valuable insights into the subject of suicide. This paper offers a total view of the author's contributions to suicidology, through a study of suicidal behavior in his fiction, journalism and in his own life experiences. Dostoevsky's writings are testimony to the continuous and brilliant interrelations between his fictional and journalistic narratives, his understanding of individual, family and group dynamics, his intellectual search for the roots of ideology, and the authentic experience and spiritual quest of his life.

  3. [Suicide in the Elderly].

    Science.gov (United States)

    Velásquez Suarez, Juliana María

    2013-01-01

    Suicide is a public health problem worldwide, with multiple features and risk factors. It has some common and unique trends in each phase across the lifespan. To review the medical literature related to suicide in the elderly, in order to determine the current status of this problem in the world, and especially in Colombia. Literature review. There is a high volume of articles about suicide in general, even in Colombia, with many papers describing the problem in a comprehensive manner, but there is a need for more studies and publications on the scope of this problem in the elderly. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  4. Suicide bomber detection

    Science.gov (United States)

    Alexander, Naomi; Callejero, Carlos; Fiore, Franco; Gómez, Ignacio; Gonzalo, Ramón; Enríquez de Luna, Álvaro; Ederra, Iñigo; Palacios, Inés

    2009-05-01

    The chance of suicide bomber attacks against troops in the Theatre of Operations is currently quite high. Most of the time checkpoints and compound gates are not equipped with the appropriate equipment to screen for potential suicide bombers. The ultimate solution would be to be able to perform stand-off screening under various weather conditions whilst avoiding contact between Force Protection personnel and potential suicide bombers. Radiation in the millimeterwave and the lower Terahertz range, having the useful property of being able to penetrate clothing in addition to fog and rain, makes it a clear candidate for imaging in this situation. A study has been made simulating real case scenarios to test practical detection performance and stand-off distances at a range of frequencies in this band, the results of which will be presented.

  5. [Suicidal poisoning with benzodiazepines].

    Science.gov (United States)

    Chodorowski, Z; Sein Anand, J

    1997-01-01

    In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.

  6. Labeling of thymidine analog with an organometallic complex of technetium-99m for diagnostic of cancer: radiochemical and biological evaluation

    International Nuclear Information System (INIS)

    Santos, Rodrigo Luis Silva Ribeiro

    2007-01-01

    Thymidine analogs have been labeled with different radioisotopes due to their potential in monitoring the uncontrollable cell proliferation. Considering that the radioisotopes technetium-99m still keep a privileged position as a marker due to its chemical and nuclear properties, this dissertation was constituted by the developed of a new technique of labeling of thymidine analog with 99m Tc, by means of the organometallic complex. The aims of this research were: synthesis of the organometallic complex technetium-99m-carbonyl, thymidine labeling with this precursor, evaluation of stability, and radiochemical e biological evaluation with healthy and tumor-bearing animals. The preparation of the organometallic precursor, using the CO gas, was easily achieved, as well as the labeling of thymidine with this precursor, resulting itself a radiochemical pureness of ≥ 97% and ≥ 94%, respectively. Chromatography systems with good levels of trustworthiness were used, ensuring the qualification and quantification of the radiochemical samples. The result of in vitro testing of lipophilicity disclosed that the radiolabeled complex is hydrophilic, with a partition coefficient (log P) of -1.48. The precursor complex and the radiolabeled have good radiochemical stability up to 6 h in room temperature. The cysteine and histidine challenge indicated losses between 8 and 1 1 % for concentrations until 300 mM. The biodistribution assay in healthy mice revealed rapid blood clearance and low uptake by general organs with renal and hepatobiliary excretion. The tumor concentration was low with values of 0.28 and 0.18 %ID/g for lung and breast cancer, respectively. The results imply more studies in other tumor models or the modification of the structure of the organic molecule that act like ligand. (author)

  7. Syntheses of pyrimidine acyclic nucleoside phosphonates as potent inhibitors of thymidine phosphorylase (PD-ECGF) from SD-lymphoma

    Czech Academy of Sciences Publication Activity Database

    Pomeisl, Karel; Votruba, Ivan; Holý, Antonín; Pohl, Radek

    2007-01-01

    Roč. 26, 8/9 (2007), s. 1025-1028 ISSN 1525-7770. [International Roundtable /17./. Bern, 03.09.2006-07.09.2006] R&D Projects: GA MŠk 1M0508 Grant - others:Descartes Prize(XE) HPAW-CT-2002-9001 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * thymidine phosphorylase * pyrimidines * FPMP derivatives * fluor ination Subject RIV: CC - Organic Chemistry Impact factor: 0.723, year: 2007

  8. Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase

    DEFF Research Database (Denmark)

    Mikkelsen, Niels Egil; Munch-Petersen, Birgitte; Eklund, Hans

    2008-01-01

    The Drosophila Melanogaster multisubstrate deoxyribonucleoside kinase (dNK) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a pro...

  9. Risk factors for suicide in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Koch-Henriksen, N; Stenager, E

    1996-01-01

    suicides with the 1950-1985 onset cohort patients in the DSMR as to distribution of age at onset, presenting symptoms, and time from onset to diagnosis. We reviewed sociodemographic data, age of onset, the course of the disease, recent deterioration, type of deterioration, Kurtzke Disability Status Scale...... (DSS) score, previous mental disorder, type of mental disorder, previous suicide attempts, expression of suicidal intentions, circumstances at suicide, and suicide method for all MS patients who had committed suicide. In order to characterize MS suicides with respect to risk factors, comparisons were...... made for male and female suicides and for various groups of MS suicides according to disability status. RESULTS: The male suicide patients were characterized by a tendency to commit suicide in the age interval 40-49 years, by the use of a violent suicide method, by previous suicidal behaviour...

  10. Dietary arginine level and 3H-thymidine incorporation into DNA in normal and regenerating liver of weanling rats

    International Nuclear Information System (INIS)

    Zimber, A.; Elliott, T.S.; Visek, W.J.

    1986-01-01

    Male weanling Sprague-Dawley rats were fed graded amounts of arginine (0.25% - 2%) in a crystalline L-amino acid diet for 10 days. Feed intake was decreased only in the rats receiving 0.25% Arg in the diet. Weight gain and growth efficiency were lower in the rats receiving 0.25% and 0.5% dietary arginine. Orotic acid excretion was elevated 400 fold in the rats receiving less than 1% dietary arginine. Liver weights were not significantly different among groups. DNA concentration/g liver was 10% lower in the rats receiving 0.25% dietary arginine. Rats receiving less than 1% arginine had 17% less RNA/g liver and 77% less 3 H-thymidine incorporation into liver DNA. After partial hepatectomy (PH) 3 H-thymidine incorporation into liver DNA was increased by 23% on rats receiving 0.5 dietary arginine compared to sham operated controls (SOC) receiving the same diet. Incorporation of 3 H-thymidine was unchanged in PH rats as compared with SOC rats receiving 0.25% Arg. These data indicate that at least 1% of dietary arginine is required to maintain normal protein metabolism in growing male rats. There were no significant differences in any of the parameters measured when dietary Arg was 1% or 2% of the diet

  11. In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Khalid Mohammed; Ghufran, Mehreen; Ali, Muhammad

    2016-10-01

    Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Acute non-stochastic effect of very low dose whole-body exposure, a thymidine equivalent serum factor

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Muehlensiepen, H.; Porschen, W.; Booz, J.

    1982-01-01

    Whole-body irradiation of mice causes the dose-dependent appearance of a humoral factor in blood serum which inhibits incorporation of 125-IUdR into tissue culture cells. This factor appears even at doses below 0.01 Gy gamma irradiation and thus is probably not related to cell death. Data are presented relating this humoral factor to thymidine. Since at low doses the target size for this effect was calculated to be the entire cell, a cellular effect is postulated linking the site of few primary absorption events, anywhere in the cell, with the cellular membrane, thus causing changes in membrane charge, structure and/or fluidity. This may lead to blocking thymidine acceptance by the cell, and thus would cause a pile-up of thymidine in the reutilization pathway in peripheral blood and would give rise to the observed effect. The effect appears as a temporary disturbance of the physiological equilibrium and should not be related at present to any cellular damage. The acute low-dose effect described has implications for the measurement of low-dose exposure by biological dosimeters and on basic research on membrane function. (author)

  13. Suicidal ideation among Malaysian adolescents.

    Science.gov (United States)

    Ahmad, NoorAni; Cheong, Siew Man; Ibrahim, Nurashikin; Rosman, Azriman

    2014-09-01

    Adolescence is the time of greatest risk for the first onset of suicidal behaviors. This study aimed to identify the risk and protective factors associated with suicidal ideation among Malaysian adolescents. Data from the 2012 Malaysia Global School-based Student Health Survey, a nationwide study using a 2-stage cluster sampling design, were analyzed. The survey used a self-administered validated bilingual questionnaire and the Depression Anxiety and Stress Scale. The prevalence of suicidal ideation was 7.9%. Analysis revealed that suicidal ideation was positively associated with depression, anxiety, stress, substance use, being bullied, and being abused at home, either physically or verbally. In addition, suicidal ideation was significantly higher among females and among the Indians and Chinese. Having close friends and married parents were strongly protective against suicidal ideation. Understanding the risk and protective factors is important in providing comprehensive management for suicidal ideation. © 2014 APJPH.

  14. Suicide among older psychiatric inpatients

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Zarit, Steven H; Tu, Xin

    2006-01-01

    .1-0.3). In combination with other types of disorder, affective disorders were found to modify an increased risk of suicide. First versus later admission for depression was a better predictor for suicide than age at first hospitalization for depression (before or after age 60 years). More than half of suicides occurred......OBJECTIVE: Older adults have elevated suicide rates, especially in the presence of a psychiatric disorder, yet not much is known about predictors for suicide within this high-risk group. The current study examines the characteristics associated with suicide among older adults who are admitted...... to a psychiatric hospital. METHOD: All persons aged 60 and older living in Denmark who were hospitalized with psychiatric disorders during 1990-2000 were included in the study. Using a case-control design and logistic regression analysis, the authors calculated the suicide risk associated with specific patient...

  15. Detecting suicidality on Twitter

    Directory of Open Access Journals (Sweden)

    Bridianne O'Dea

    2015-05-01

    Full Text Available Twitter is increasingly investigated as a means of detecting mental health status, including depression and suicidality, in the population. However, validated and reliable methods are not yet fully established. This study aimed to examine whether the level of concern for a suicide-related post on Twitter could be determined based solely on the content of the post, as judged by human coders and then replicated by machine learning. From 18th February 2014 to 23rd April 2014, Twitter was monitored for a series of suicide-related phrases and terms using the public Application Program Interface (API. Matching tweets were stored in a data annotation tool developed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO. During this time, 14,701 suicide-related tweets were collected: 14% were randomly (n = 2000 selected and divided into two equal sets (Set A and B for coding by human researchers. Overall, 14% of suicide-related tweets were classified as ‘strongly concerning’, with the majority coded as ‘possibly concerning’ (56% and the remainder (29% considered ‘safe to ignore’. The overall agreement rate among the human coders was 76% (average κ = 0.55. Machine learning processes were subsequently applied to assess whether a ‘strongly concerning’ tweet could be identified automatically. The computer classifier correctly identified 80% of ‘strongly concerning’ tweets and showed increasing gains in accuracy; however, future improvements are necessary as a plateau was not reached as the amount of data increased. The current study demonstrated that it is possible to distinguish the level of concern among suicide-related tweets, using both human coders and an automatic machine classifier. Importantly, the machine classifier replicated the accuracy of the human coders. The findings confirmed that Twitter is used by individuals to express suicidality and that such posts evoked a level of concern that warranted

  16. The development and validation of an immunoassay for the measurement of anti-thymidine phosphorylase antibodies in mouse and dog sera

    OpenAIRE

    Gasson, C; Levene, M; Bax, BE

    2013-01-01

    Erythrocyte encapsulated thymidine phosphorylase (EE-TP) is under development as an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a fatal metabolic disorder resulting from an inherited deficiency of the enzyme thymidine phosphorylase. We report here the development and validation of a sensitive electrochemiluminescent (ECL) bridging immunoassay to support Good Laboratory Practice (GLP)-compliant preclinical safety studies of EE-TP in the mouse a...

  17. 3H-thymidine labelling of DNA of radiosensitive organs of rats irradiated under alpine conditions and after adaptation to hypoxia in the altitude chamber

    International Nuclear Information System (INIS)

    Gusejnov, F.T.; Egorov, I.A.; Gladilin, K.L.; Farber, Yu.V.

    1979-01-01

    Preliminary adaptation of rats of high altitude conditions (3200 m) and training in the altitude chamber at the same imitated altitude inhibit 3 H-thymidine labelling of thymus DNA both shortly (26 h) and later (20 and 30 days) after irradiation. Whether the thymidine incorporation is activated or delayed depends on conditions of pretreatment. The data obtained are discussed from the point of view of the raioprotective effect of preadaptation of animals to high-altitude hypoxia

  18. Parental affectionless control and suicidality.

    Science.gov (United States)

    Goschin, Simona; Briggs, Jessica; Blanco-Lutzen, Sally; Cohen, Lisa J; Galynker, Igor

    2013-10-01

    Although poor parental bonding is a known risk factor for suicidality, current literature is inconsistent about the relative role of low parental care and parental overprotection, as well as the combination of the two, termed "affectionless control". This review presents the current state of knowledge of the relationship between suicidality and these two aspects of parental bonding. The computerized databases Medline, PubMed, PsychINFO, PsychLit, and Google Scholar were searched using combinations of the following keywords: suicidality, suicide, suicide attempt, suicidal behavior, parental bonding, and parental bonding instrument. Using the results, we reviewed the reports on the relationship between suicidality and parental bonding as measured by validated parental bonding instruments. Twelve papers were analyzed. All of them used the parental bonding instrument (PBI) and one used both the PBI and the object representation inventory (ORI). Most reports agreed that, in mothers, either lack of maternal care and/or overprotection was associated with an increase in suicidal behavior, while in fathers only low care was consistently associated with suicidality. This lack of constancy with regard to the effect of paternal overprotection appears to be due to cultural differences in fathers' role in child rearing. With these differences acknowledged, affectionless control in both parents emerges as the parenting style most strongly associated with suicidal behavior. Common methodological problems included low numbers of subjects, inconsistent control groups, and the lack of a uniform definition of suicidality. Despite methodological limitations, current literature consistently indicates that parental affectionless control is associated with suicidal behavior. Recognizing affectionless control as a risk factor for suicide and developing early interventions aimed at modifying affectionless and overprotective parenting style in families with a history of affective disorders

  19. Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters.

    Science.gov (United States)

    Rajalin, Mia; Hirvikoski, Tatja; Jokinen, Jussi

    2013-05-15

    Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters. A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale. Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records. The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Copycat Suicide Induced by Entertainment Celebrity Suicides in South Korea

    Science.gov (United States)

    Jang, Soo Ah; Sung, Ji Min; Park, Jin Young

    2016-01-01

    Objective Throughout the past several years, there have been a number of entertainment celebrity suicides in South Korea. The aim of this study was to investigate the clustering of suicides following celebrities' suicides in South Korea from 2005 to 2008, particularly according to certain characteristics. Methods Seven celebrity suicides were examined and defined using the Korean Integrated Newspaper Database System (KINDS) and from these, we considered four affected periods occurring 28 days after each celebrity's suicide. A Poisson time-series autoregression model was used to estimate the relative risk of the total suicide number for each affected period from 2005 to 2008. Logistic regression analysis was performed to investigate whether there were specific increases in the numbers of suicides in subgroups matching each celebrity. Results There were significant increases in the risk of suicide during the affected periods. Remarkable increases were found in the subgroups matching each celebrity, especially in the group in which all factors (sex, age, and method) were similar. Conclusion This study provides confirmation that a significant copycat effect was induced by these celebrities' suicides, especially among people who identified more with the celebrities. This implies that countermeasures for upright media coverage of celebrity suicides should be discussed and practiced properly in South Korea. PMID:26766949

  1. Suicidality in chronic pain: predictors of suicidal ideation in fibromyalgia.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2015-04-01

    Fibromyalgia (FM) has been associated with a higher prevalence of suicidal behavior. Nevertheless, much remains unknown about suicide risk factors for this chronic pain disorder. In the present study, the relationship of suicidal ideation in FM with a number of sociodemographic, clinical, and psychological variables was analyzed. One hundred seventeen women with Fibromyalgia were assessed. The procedure included the exploration of sleep problems (Pittsburgh Sleep Quality Index), depression (Beck Depression Inventory [BDI]), health-related quality of life (SF-36 and Fibromyalgia Impact Questionnaire), the core symptoms of FM (visual analogue scales), and algometry of tender points. Suicidal ideation was evaluated by item 9 of the BDI. Patients with presence vs. absence of suicidal ideation were compared in all the variables studied. The prevalence of suicidal ideation among FM patients was 32.5%. Significant differences between patients with vs. without suicidal ideas emerged mainly for the various indices of depression. Patients with suicidal ideation also reported higher levels of anxiety, more day dysfunction due to sleepiness and more limitations due to emotional and physical problems. Logistic regression analysis revealed that cognitive depression symptoms such as BDI Self-Blame cluster are the more closely related to suicide ideation. The presence of suicidal ideation in FM patients is closely related to comorbid depression, anxiety and to a higher impact of the disease in daily life. © 2014 World Institute of Pain.

  2. Copycat Suicide Induced by Entertainment Celebrity Suicides in South Korea.

    Science.gov (United States)

    Jang, Soo Ah; Sung, Ji Min; Park, Jin Young; Jeon, Woo Taek

    2016-01-01

    Throughout the past several years, there have been a number of entertainment celebrity suicides in South Korea. The aim of this study was to investigate the clustering of suicides following celebrities' suicides in South Korea from 2005 to 2008, particularly according to certain characteristics. Seven celebrity suicides were examined and defined using the Korean Integrated Newspaper Database System (KINDS) and from these, we considered four affected periods occurring 28 days after each celebrity's suicide. A Poisson time-series autoregression model was used to estimate the relative risk of the total suicide number for each affected period from 2005 to 2008. Logistic regression analysis was performed to investigate whether there were specific increases in the numbers of suicides in subgroups matching each celebrity. There were significant increases in the risk of suicide during the affected periods. Remarkable increases were found in the subgroups matching each celebrity, especially in the group in which all factors (sex, age, and method) were similar. This study provides confirmation that a significant copycat effect was induced by these celebrities' suicides, especially among people who identified more with the celebrities. This implies that countermeasures for upright media coverage of celebrity suicides should be discussed and practiced properly in South Korea.

  3. Suicidal behaviour and suicide prevention in later life.

    Science.gov (United States)

    Draper, Brian M

    2014-10-01

    Despite a general decline in late life suicide rates over the last 30 years, older people have the highest rates of suicide in most countries. In contrast, non-fatal suicidal behaviour declines with age and more closely resembles suicide than in younger age groups. There are difficulties in the detection and determination of pathological suicidal ideation in older people. Multiple factors increase suicide risk ranging from distal early and mid-life issues such as child abuse, parental death, substance misuse and traumatic life experiences to proximal precipitants in late life such as social isolation and health-related concerns. Clinical depression is the most frequently identified proximal mental health concern and in many cases is a first episode of major depression. Recent studies have identified changes on neuroimaging and neurocognitive factors that might distinguish suicidal from non-suicidal depression in older people. Strategies for suicide prevention need to be 'whole of life' and, as no single prevention strategy is likely to be successful alone, a multi-faceted, multi-layered approach is required. This should include optimal detection and management of depression and of high risk individuals as available evidence indicates that this can reduce suicidal behaviour. How best to improve the quality of depression management in primary and secondary care requires further research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Managing suicidal adolescents

    African Journals Online (AJOL)

    2008-05-09

    May 9, 2008 ... As suicidal ideation and behaviour are linked to the presence of depression it is important that clinicians first assess (i) depressive ... thereafter referral for psychotherapy by a clinical psychologist or psychiatrist. ... are related to interpersonal conflicts (often with parents), it is crucial that intervention involves ...

  5. Suicide with hydrogen sulfide.

    Science.gov (United States)

    Sams, Ralph Newton; Carver, H Wayne; Catanese, Charles; Gilson, Thomas

    2013-06-01

    This presentation will address the recent rise of suicide deaths resulting from the asphyxiation by hydrogen sulfide (H2S) gas.Hydrogen sulfide poisoning has been an infrequently encountered cause of death in medical examiner practice. Most H2S deaths that have been reported occurred in association with industrial exposure.More recently, H2S has been seen in the commission of suicide, particularly in Japan. Scattered reports of this phenomenon have also appeared in the United States.We have recently observed 2 intentional asphyxial deaths in association with H2S. In both cases, the decedents committed suicide in their automobiles. They generated H2S by combining a sulfide-containing tree spray with toilet bowl cleaner (with an active ingredient of hydrogen chloride acid). Both death scenes prompted hazardous materials team responses because of notes attached to the victims' car windows indicating the presence of toxic gas. Autopsy findings included discoloration of lividity and an accentuation of the gray matter of the brain. Toxicology testing confirmed H2S exposure with the demonstration of high levels of thiosulfate in blood.In summary, suicide with H2S appears to be increasing in the United States.

  6. Suicide in Canada

    National Research Council Canada - National Science Library

    Leenaars, Antoon A

    1998-01-01

    ... provides long-awaited information that focuses specifically on Canada. It addresses suicide as a multidimensional problem with biological, psychological, cultural, sociological, personal, and philosophical aspects. The contributions integrate both critical analysis and personal experience. There are accounts from Inuit elders, fr...

  7. Mental Pain and Suicide

    DEFF Research Database (Denmark)

    Verrocchio, Maria Cristina; Carrozzino, Danilo; Marchetti, Daniela

    2016-01-01

    a systematic review analyzing the relationship between mental pain and suicide by providing a qualitative data synthesis of the studies. Methods: We have conducted, in accordance with PRISMA guidelines, a systematic search for the literature in PubMed, Web Of Science, and Scopus. Search terms were "mental pain...

  8. Suicide: Neurochemical Approaches

    Directory of Open Access Journals (Sweden)

    Ritabrata Banerjee

    2013-10-01

    Full Text Available Despite the devastating effect of suicide on numerous lives, there is still a dearthof knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF and Nerve growth factor (NGF are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors trk B and trk A respectively. The present study was performed to examine whether the expression profiles of BDNF and/or trk B as well as NGF and/or trk A were altered in postmortem brain in subjects who commitsuicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed in hippocampus obtained 21 suicide subjects and 19 non-psychiatric control subjects. The protein and mRNA levels of BDNF, trk B and NGF, trk A were determined with Sandwich ELISA, Western Blot and RT PCR respectively. Given the importance of BDNFand NGF along with their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, Trk B and NGF, Trk A in both protein and mRNA levels of postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

  9. Suicide and multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Stenager, Egon; Koch-Henriksen, Nils

    1992-01-01

    In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...

  10. Electroconvulsive Therapy and Suicide.

    Science.gov (United States)

    Tanney, Bryan L.

    1986-01-01

    When the effectiveness and mortality-morbidity of electroconvulsive therapy (ECT) are compared with those of drug therapies, it appears that ECT is an effective and preferred treatment strategy. It remains underutilized as a modality of suicide prevention. Addresses controversies that presently limit the use of this treatment. (Author/ABB)

  11. Chechen Suicide Bombers

    Science.gov (United States)

    2007-12-18

    NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Army Foreign Military Studies Office (FMSO),731...has been the most common theme underlying the various motivations that drive Chechen-related suicide terrorism. Drugging and hypnosis have also played a

  12. Psychotherapy for Suicidal Clients.

    Science.gov (United States)

    Lester, David

    1994-01-01

    Reviews various systems of psychotherapy for suitability for suicidal clients. Discusses psychoanalysis, cognitive therapy, primal therapy, transactional analysis, Gestalt therapy, reality therapy, person-centered therapy, existential analysis, and Jungian analysis in light of available treatment options. Includes 36 citations. (Author/CRR)

  13. Suicide in serial killers.

    Science.gov (United States)

    Lester, David; White, John

    2010-02-01

    In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested.

  14. Stigmatization and Suicide Bereavement

    Science.gov (United States)

    Feigelman, William; Gorman, Bernard S.; Jordan, John R.

    2009-01-01

    With survey data collected primarily from peer support group participants, the authors compared stigmatization responses of 462 parents losing children to suicide with 54 other traumatic death survivors and 24 child natural death survivors. Parents who encountered harmful responses and strained relations with family members and non-kin reported…

  15. [Autism spectrum disorder and suicidality].

    Science.gov (United States)

    Huguet, G; Contejean, Y; Doyen, C

    2015-09-01

    Most studies on suicide exclude subjects with autism spectrum disorders, yet there is a risk group. The purpose of this article is to present the data in the literature regarding the clinical and epidemiological characteristics of suicidality in subjects with autism spectrum disorders and to identify the factors that promote the transition to action. This review was carried out using the data set collected in Medline PubMed, items with "autism spectrum disorder", "pervasive developmental disorder", "Asperger's syndrome", "suicide", "suicide attempt", and "suicide behavior". In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. Suicidal ideation and morbid preoccupation are particularly common in adolescents and young adults. Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects. The methods used are often violent and potentially lethal or fatal in two cases published. Suicide risk depends on many factors that highlight the vulnerability of these subjects, following autistic and developmental symptoms. Vulnerability complicating the diagnosis of comorbid depressive and anxiety disorders are major factors associated with suicidality. Vulnerability but also directly related to suicidality, since the origin of physical and sexual abuse and victimization by peers assigning them the role of "scapegoat" are both responsible for acting out. Given the diversity of factors involved in the risk of suicide in this population, this does not validate "a" program of intervention, but the intervention of "customized programs". Their implementation should be as early as possible in order to treat

  16. Clusters of suicides and suicide attempts: detection, proximity and correlates.

    Science.gov (United States)

    Too, L S; Pirkis, J; Milner, A; Spittal, M J

    2017-10-01

    A suicide cluster is defined as a higher number of observed cases occurring in space and/or time than would typically be expected. Previous research has largely focused on identifying clusters of suicides, while there has been comparatively limited research on clusters of suicide attempts. We sought to identify clusters of both types of behaviour, and having done that, identify the factors that distinguish suicide attempts inside a cluster from those that were outside a cluster. We used data from Western Australia from 2000 to 2011. We defined suicide attempts as admissions to hospital for deliberate self-harm and suicides as deaths due to deliberate self-harm. Using an analytic strategy that accounted for the repetition of attempted suicide within a cluster, we performed spatial-temporal analysis using Poisson discrete scan statistics to detect clusters of suicide attempts and clusters of suicides. Logistic regression was then used to compare clustered attempts with non-clustered attempts to identify risk factors for an attempt being in a cluster. We detected 350 (1%) suicide attempts occurring within seven spatial-temporal clusters and 12 (0.6%) suicides occurring within two spatial-temporal clusters. Both of the suicide clusters were located within a larger but later suicide attempt cluster. In multivariate analysis, suicide attempts by individuals who lived in areas of low socioeconomic status had higher odds of being in a cluster than those living in areas of high socioeconomic status [odds ratio (OR) = 29.1, 95% confidence interval (CI) = 6.3-135.5]. A one percentage-point increase in the proportion of people who had changed address in the last year was associated with a 60% increase in the odds of the attempt being within a cluster (OR = 1.60, 95% CI = 1.29-1.98) and a one percentage-point increase in the proportion of Indigenous people in the area was associated with a 7% increase in the suicide being within a cluster (OR = 1.07, 95% CI = 1.00-1.13). Age

  17. VA Suicide Prevention Applications Network

    Science.gov (United States)

    Stephens, Brady; Morley, Sybil; Thompson, Caitlin; Kemp, Janet; Bossarte, Robert M.

    2016-01-01

    Objectives: The US Department of Veterans Affairs’ Suicide Prevention Applications Network (SPAN) is a national system for suicide event tracking and case management. The objective of this study was to assess data on suicide attempts among people using Veterans Health Administration (VHA) services. Methods: We assessed the degree of data overlap on suicide attempters reported in SPAN and the VHA’s medical records from October 1, 2010, to September 30, 2014—overall, by year, and by region. Data on suicide attempters in the VHA’s medical records consisted of diagnoses documented with E95 codes from the International Classification of Diseases, Ninth Revision. Results: Of 50 518 VHA patients who attempted suicide during the 4-year study period, data on fewer than half (41%) were reported in both SPAN and the medical records; nearly 65% of patients whose suicide attempt was recorded in SPAN had no data on attempted suicide in the VHA’s medical records. Conclusion: Evaluation of administrative data suggests that use of SPAN substantially increases the collection of data on suicide attempters as compared with the use of medical records alone, but neither SPAN nor the VHA’s medical records identify all suicide attempters. Further research is needed to better understand the strengths and limitations of both systems and how to best combine information across systems. PMID:28123228

  18. Telomerase activated thymidine analogue pro-drug is a new molecule targeting hepatocellular carcinoma

    Science.gov (United States)

    Tarocchi, Mirko; Polvani, Simone; Peired, Anna Julie; Marroncini, Giada; Calamante, Massimo; Ceni, Elisabetta; Rhodes, Daniela; Mello, Tommaso; Pieraccini, Giuseppe; Quattrone, Alessandro; Luchinat, Claudio; Galli, Andrea

    2014-01-01

    Background & Aims Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although hepatectomy and transplantation have significantly improved survival, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Sustained activation of telomerase is essential for the growth and progression of HCC, suggesting that telomerase is a rational target for HCC therapy. Therefore, we developed a thymidine analogue pro-drug, acycloguanosyl-5′-thymidyltriphosphate (ACV-TP-T), which is specifically activated by telomerase in HCC cells and investigated its anti-tumour efficacy. Methods First, we verified in vitro whether ACV-TP-T was a telomerase substrate. Second, we evaluated proliferation and apoptosis in murine (Hepa1-6) and human (Hep3B, HuH7, HepG2) hepatic cancer cells treated with ACV-TP-T. Next, we tested the in vivo treatment efficacy in HBV transgenic mice that spontaneously develop hepatic tumours, and in a syngeneic orthotopic murine model where HCC cells were implanted directly in the liver. Results In vitro characterization provided direct evidence that the pro-drug was actively metabolized in liver cancer cells by telomerase to release the active form of acyclovir. Alterations in cell cycle and apoptosis were observed following in vitro treatment with ACV-TP-T. In the transgenic and orthotopic mouse models, treatment with ACV-TP-T reduced tumour growth, increased apoptosis, and reduced the proliferation of tumour cells. Conclusions ACV-TP-T is activated by telomerase in HCC cells and releases active acyclovir that reduces proliferation and induces apoptosis in human and murine liver cancer cells. This pro-drug holds a great promise for the treatment of HCC. PMID:24862448

  19. Family history of suicide and high motor impulsivity distinguish suicide attempters from suicide ideators among college students.

    Science.gov (United States)

    Wang, Yong-Guang; Chen, Shen; Xu, Zhi-Ming; Shen, Zhi-Hua; Wang, Yi-Quan; He, Xiao-Yan; Cao, Ri-Fang; Roberts, David L; Shi, Jian-Fei; Wang, Yi-Qiang

    2017-07-01

    Suicide in college students has become an important public health issue in China. The aim of this study was to identify the differences between suicide attempters and suicide ideators based on a cross-sectional survey. Our results indicate that although female gender, positive screening for psychiatric illness, positive family history of suicide, elevated overall impulsivity, and elevated motor impulsivity were correlated with suicidal ideation, only positive family history of suicide and high motor impulsivity could differentiate suicide attempters from suicidal ideators. Future research with a longitudinal and prospective study design should be conducted to confirm these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Income, employment and suicidal behavior.

    Science.gov (United States)

    Kalist, David E; Molinari, Noelle-Angelique M; Siahaan, Freddy

    2007-12-01

    Little is known about the labor market outcomes of people who have attempted suicide or thought about suicide. We used micro-level data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions 2001-2002 to examine the effects of suicidal behavior on income and employment. The data provide a representative sample of the U.S. population, with its primary purpose to provide information on alcohol use disorders for the civilian non-institutionalized population aged 18 and over. The data include employment, income, and other socioeconomic and demographic information on respondents. Since the survey included 43,093 people, the data include a large number of respondents who attempted suicide or thought about committing suicide. We estimated earnings regressions and logit and ordered logit employment regressions. We used methods of IV estimation as well as two stage linear probability models to address potential endogeneity of suicidal behavior while estimating regressions separately by sex, since there are significant differences in suicide rates, suicide attempts, and suicidal ideation between men and women. We find that suicide attempts and suicidal ideation are negatively related to personal income and the probability of employment. The effects differ by sex. Men and women who attempted suicide had mean earnings lower by 16 and 13 percent, respectively. This amount reflects the combined effect of suicidal behavior and mental illness. With instrumental variable regression, the magnitude of the effects becomes larger-for example, as much as 50 percent decrease in the income of males who attempted suicide. Thoughts of suicide negatively affect income but to a smaller extent. Logit and ordered logit regressions indicate that attempted suicide reduces the probability of fulltime employment by over 20 percentage points for men and approximately 17 percentage points for women. People who engaged in suicidal behavior reported significantly

  1. Suicide attempts in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Elsebeth Nylev; Jensen, Børge; Stenager, Maria

    2011-01-01

    The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating...... therapy compared with untreated patients. The Danish MS Registry, the Danish MS Treatment Registry and the Suicide Attempt Registry are linked and merged together using a person identification number given to all persons residing in Denmark. Among 404 MS patients, 15 patients had attempted suicide......, although no increased risk for suicide attempts was found in MS patients. No difference in number of suicide attempts in treated and untreated patients was found....

  2. Suicide, Guns, and Public Policy

    Science.gov (United States)

    Miller, Sara A.

    2013-01-01

    Suicide is a serious public health concern that is responsible for almost 1 million deaths each year worldwide. It is commonly an impulsive act by a vulnerable individual. The impulsivity of suicide provides opportunities to reduce the risk of suicide by restricting access to lethal means. In the United States, firearms, particularly handguns, are the most common means of suicide. Despite strong empirical evidence that restriction of access to firearms reduces suicides, access to firearms in the United States is generally subject to few restrictions. Implementation and evaluation of measures such as waiting periods and permit requirements that restrict access to handguns should be a top priority for reducing deaths from impulsive suicide in the United States. PMID:23153127

  3. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  4. Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A

    Directory of Open Access Journals (Sweden)

    Mustafa Almasry

    2016-11-01

    Full Text Available Background/Aims: The serine/threonine protein phosphatase 1 and 2a inhibitor Calyculin A may trigger suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+] i. Eryptosis is fostered by activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, and D4476 sensitive casein kinase. Eryptosis may further involve zVAD sensitive caspases. The present study explored, whether Calyculin A induces eryptosis and, if so, whether its effect requires Ca2+ entry, kinases and/or caspases Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, and [Ca2+] i from Fluo-3 fluorescence, as determined by flow cytometry. Results: A 48 hours exposure of human erythrocytes to Calyculin A (≥ 2.5 nM significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter and significantly increased Fluo-3 fluorescence. The effect of Calyculin A on annexin-V-binding was significantly blunted by removal of extracellular Ca2+, by staurosorine (1 µM, SB203580 (2 µM, D4476 (10 µM, and zVAD (10 µM. Conclusions: Calyculin A triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part requiring Ca2+ entry, kinase activity and caspase activation.

  5. Nurses' experiences of patient suicide and suicide attempts in an acute unit

    OpenAIRE

    DOYLE, LOUISE; DOYLE, LOUISE

    2008-01-01

    PUBLISHED Suicide and suicide attempts in Ireland have increased dramatically in the last twenty years. Many of the presentations of suicide attempts to Emergency Departments are recommended an admission to an acute mental health unit. A psychiatric staff nurse working in an acute mental health setting has a high chance of experiencing a patient suicide or suicide attempt during their career. The occurrence of an inpatient suicide or suicide attempt is unquestionably an overwhelmingly stre...

  6. Suicide among Arab-Americans.

    Directory of Open Access Journals (Sweden)

    Abdulrahman M El-Sayed

    2011-02-01

    Full Text Available Arab-American (AA populations in the US are exposed to discrimination and acculturative stress-two factors that have been associated with higher suicide risk. However, prior work suggests that socially oriented norms and behaviors, which characterize recent immigrant ethnic groups, may be protective against suicide risk. Here we explored suicide rates and their determinants among AAs in Michigan, the state with the largest proportion of AAs in the US.ICD-9/10 underlying cause of death codes were used to identify suicide deaths from among all deaths in Michigan between 1990 and 2007. Data from the 2000 U.S. Census were collected for population denominators. Age-adjusted suicide rates among AAs and non-ethnic whites were calculated by gender using the direct method of standardization. We also stratified by residence inside or outside of Wayne County (WC, the county with the largest AA population in the state. Suicide rates were 25.10 per 100,000 per year among men and 6.40 per 100,000 per year among women in Michigan from 1990 to 2007. AA men had a 51% lower suicide rate and AA women had a 33% lower rate than non-ethnic white men and women, respectively. The suicide rate among AA men in WC was 29% lower than in all other counties, while the rate among AA women in WC was 20% lower than in all other counties. Among non-ethnic whites, the suicide rate in WC was higher compared to all other counties among both men (12% and women (16%.Suicide rates were higher among non-ethnic white men and women compared to AA men and women in both contexts. Arab ethnicity may protect against suicide in both sexes, but more so among men. Additionally, ethnic density may protect against suicide among Arab-Americans.

  7. Does Religiosity Predict Suicidal Behavior?

    Directory of Open Access Journals (Sweden)

    David Lester

    2017-10-01

    Full Text Available Research was reviewed on whether self-report measures of religiosity were a protective factor against suicidal behaviors. It was found that scores on Francis’s measure of religiosity was negatively associated with non-lethal suicidal behavior (ideation and attempts, a protective effect. Similarly, it was found that intrinsic religiosity (but not extrinsic religiosity was negatively associated with non-lethal suicidal behaviors. However, these associations were weak. Research is needed on the issue whether counselors can use their patients’ religiosity to reduce the risk of dying by suicide.

  8. Medicine poisoning in suicidal pathology

    Directory of Open Access Journals (Sweden)

    Ljušic Dragan

    2015-01-01

    Full Text Available Introduction: Investigations shows that on every realized suicide comes 8 to 25 non realized attempts. Individuals which tried suicide with medicine poisoning mostly quote that they have been overwhelmed with feelings and thoughts which was unbearable in that moment. They wished to escape from that unbearable situation or they lost self control. Between individuals whom tried suicide with medicine poisoning, desire to really die, to disappear was very rare. Mostly it was wish 'just to sleep a little, to take a rest, make pause'. Aim of work: to identified most frequently method for suicidal attempt in both sex and resources which was used in these purposes. Results: most frequently method for suicidal attempt for both sex in our investigation was medicine poisoning - 91,1%, veins cutting - 5,4% and jump from height - 3,6%. Mostly used medicines were anxiolytics - 55,4%, combination of different drugs - 25,0%, antidepressants - 8,9%, neuroleptics - 7,1%, drugs and alcohol - 3,6%. Most frequent method for suicidal attempt in both sex was medicine poisoning. From drugs most frequently used drugs were anxiolytics and in minimum percent combination of drugs and alcohol. After suicidal attempt 90% of individuals experienced relief because their suicidal attempt was unsuccessful. In 3% individuals there was new suicidal attempt on same way, medicine poisoning.

  9. The interpersonal theory of suicide and adolescent suicidal behavior.

    Science.gov (United States)

    Barzilay, S; Feldman, D; Snir, A; Apter, A; Carli, V; Hoven, C W; Wasserman, C; Sarchiapone, M; Wasserman, D

    2015-09-01

    Joiner's interpersonal theory of suicide (IPTS) proposes that suicide results from the combination of a perception of burdening others, social alienation, and the capability for self-harm. The theory gained some empirical support, however the overall model has yet to be tested. This study aimed to test the main predictions of IPTS in a large community sample of Israeli adolescents. 1196 Israeli Jewish and Arab high-school pupils participating in the SEYLE project completed a self-report questionnaire measuring perceived burdensomeness, thwarted belongingness, health risk behaviors, and non-suicidal self-injury (risk variables), and suicidal ideation and suicide attempts (outcome measures). The data were tested in cross-sectional regression models. Consistent with IPTS, perceived burdensomeness was found to interact with thwarted belongingness, predicting suicidal ideation. Depression mediated most of the effect of thwarted belongingness and perceived burdensomeness on suicidal ideation. Acquired capability for self-harm, as measured by health risk behaviors and direct non-suicidal self-injurious behaviors, predicted suicide attempt. However, this mechanism operated independently from ideation rather than in interaction with it, at variance with IPTS-based predictions. The cross-sectional design precludes conclusions about causality and directionality. Proxy measures were used to test the interpersonal theory constructs. The findings support some of the IPTS predictions but not all, and imply two separate pathways for suicidal behavior in adolescents: one related to internalizing psychopathology and the other to self-harm behaviors. This conceptualization has clinical implications for the differential identification of adolescents at risk for suicidal behavior and for the development of prevention strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Repeated suicide attempts and suicide among individuals with a first emergency department contact for attempted suicide

    DEFF Research Database (Denmark)

    Fedyszyn, Izabela E.; Erlangsen, Annette; Hjorthoj, Carsten

    2016-01-01

    Objective: Emergency departments are important, albeit underutilized, sites for suicide prevention. Preventive strategies and interventions could benefit from a greater understanding of factors influencing the course of suicide risk after emergency department contact due to attempted suicide...... = 1.74; 95% CI, 1.22-2.49). The cumulative rates of repeated attempts and suicide deaths in the total sample were particularly high within the first week of the index attempt, reaching 3.6% and 0.1%, respectively. Conclusions: Preventive efforts need to target the period close to discharge from....... The aim of our study was 2-fold: to identify predictors of repeated suicide attempts and suicide and to investigate the timing of these events. Methods: Data from Danish nationwide, longitudinal registers were used in this prospective, population-based study of all individuals first presenting...

  11. HOMICIDE FOLLOWED BY SUICIDE

    Directory of Open Access Journals (Sweden)

    SAMANTHA DUBUGRAS

    2007-08-01

    Full Text Available Homicide followed by suicide (H/S is a complex and poorly studied phenomenon. This research aims at identifyingH/S cases occurred in Porto Alegre from 1996 throughout 2004. Information on H/S was extracted from newspapers,police reports and interviews with the informants. From the 14 identified cases, men were the killers/suicides andwomen and children their victims. The most frequently used weapons were firearms. In general, the aggressor was animpulsive, aggressive individual showing problems within its primary supporting group, possibly suffering depressionand alcohol-addicted with criminal backgrounds (violence against the family. Events were mainly triggered by jealousy,threats or the end of a love relationship.

  12. Is thymidine glycol containing DNA a substrate of E. coli DNA mismatch repair system?

    Directory of Open Access Journals (Sweden)

    Svetlana A Perevozchikova

    Full Text Available The DNA mismatch repair (MMR system plays a crucial role in the prevention of replication errors and in the correction of some oxidative damages of DNA bases. In the present work the most abundant oxidized pyrimidine lesion, 5,6-dihydro-5,6-dihydroxythymidine (thymidine glycol, Tg was tested for being recognized and processed by the E. coli MMR system, namely complex of MutS, MutL and MutH proteins. In a partially reconstituted MMR system with MutS-MutL-MutH proteins, G/Tg and A/Tg containing plasmids failed to provoke the incision of DNA. Tg residue in the 30-mer DNA duplex destabilized double helix due to stacking disruption with neighboring bases. However, such local structural changes are not important for E. coli MMR system to recognize this lesion. A lack of repair of Tg containing DNA could be due to a failure of MutS (a first acting protein of MMR system to interact with modified DNA in a proper way. It was shown that Tg in DNA does not affect on ATPase activity of MutS. On the other hand, MutS binding affinities to DNA containing Tg in G/Tg and A/Tg pairs are lower than to DNA with a G/T mismatch and similar to canonical DNA. Peculiarities of MutS interaction with DNA was monitored by Förster resonance energy transfer (FRET and fluorescence anisotropy. Binding of MutS to Tg containing DNAs did not result in the formation of characteristic DNA kink. Nevertheless, MutS homodimer orientation on Tg-DNA is similar to that in the case of G/T-DNA. In contrast to G/T-DNA, neither G/Tg- nor A/Tg-DNA was able to stimulate ADP release from MutS better than canonical DNA. Thus, Tg residue in DNA is unlikely to be recognized or processed by the E. coli MMR system. Probably, the MutS transformation to active "sliding clamp" conformation on Tg-DNA is problematic.

  13. Is thymidine glycol containing DNA a substrate of E. coli DNA mismatch repair system?

    Science.gov (United States)

    Perevozchikova, Svetlana A; Trikin, Roman M; Heinze, Roger J; Romanova, Elena A; Oretskaya, Tatiana S; Friedhoff, Peter; Kubareva, Elena A

    2014-01-01

    The DNA mismatch repair (MMR) system plays a crucial role in the prevention of replication errors and in the correction of some oxidative damages of DNA bases. In the present work the most abundant oxidized pyrimidine lesion, 5,6-dihydro-5,6-dihydroxythymidine (thymidine glycol, Tg) was tested for being recognized and processed by the E. coli MMR system, namely complex of MutS, MutL and MutH proteins. In a partially reconstituted MMR system with MutS-MutL-MutH proteins, G/Tg and A/Tg containing plasmids failed to provoke the incision of DNA. Tg residue in the 30-mer DNA duplex destabilized double helix due to stacking disruption with neighboring bases. However, such local structural changes are not important for E. coli MMR system to recognize this lesion. A lack of repair of Tg containing DNA could be due to a failure of MutS (a first acting protein of MMR system) to interact with modified DNA in a proper way. It was shown that Tg in DNA does not affect on ATPase activity of MutS. On the other hand, MutS binding affinities to DNA containing Tg in G/Tg and A/Tg pairs are lower than to DNA with a G/T mismatch and similar to canonical DNA. Peculiarities of MutS interaction with DNA was monitored by Förster resonance energy transfer (FRET) and fluorescence anisotropy. Binding of MutS to Tg containing DNAs did not result in the formation of characteristic DNA kink. Nevertheless, MutS homodimer orientation on Tg-DNA is similar to that in the case of G/T-DNA. In contrast to G/T-DNA, neither G/Tg- nor A/Tg-DNA was able to stimulate ADP release from MutS better than canonical DNA. Thus, Tg residue in DNA is unlikely to be recognized or processed by the E. coli MMR system. Probably, the MutS transformation to active "sliding clamp" conformation on Tg-DNA is problematic.

  14. Suppression of leukocyte inhibitory factor (LIF) production and [3H]thymidine incorporation by concanavalin A-activated mononuclear cells

    International Nuclear Information System (INIS)

    Lomnitzer, R.; Rabson, A.R.

    1979-01-01

    The capacity of human mononuclear (MN) cells pretreated with concanavalin A (Con A) to suppress the activity of fresh phytohemagglutinin (PHA)-pulsed mononuclear cells was assessed. Con A-pretreated MN cells suppressed leukocyte inhibitory factor (LIF) activity in supernatants of PHA-pulsed cell cultures and [ 3 H]thymidine incorporation by these cells. Suppression was obtained in both allogeneic and autologous systems with mitomycin-treated, irradiated, or untreated Con A-induced cells. Lymphocytes from two patients that, following treatment with Con A, did not suppress mitogen-induced proliferative response of normal cells also did not suppress LIF production

  15. Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres

    Czech Academy of Sciences Publication Activity Database

    Kóšiová, Ivana; Šimák, Ondřej; Panova, Natalya; Buděšínský, Miloš; Petrová, Magdalena; Rejman, Dominik; Liboska, Radek; Páv, Ondřej; Rosenberg, Ivan

    2014-01-01

    Roč. 74, Mar 3 (2014), s. 145-168 ISSN 0223-5234 R&D Projects: GA ČR GA203/09/0820; GA ČR GA202/09/0193; GA ČR GA13-24880S; GA ČR GA13-26526S Institutional support: RVO:61388963 Keywords : phosphonate * conformationally constrained nucleotide analog * human thymidine phosphorylase * PBMC * bi-substrate-like inhibitor * Michael addition Subject RIV: CC - Organic Chemistry Impact factor: 3.447, year: 2014

  16. Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1

    DEFF Research Database (Denmark)

    Mathiesen, Sofie; Dam, Elisabeth; Roge, Birgit

    2007-01-01

    viruses from seven patients at baseline and during treatment with PFA. The phenotypic effects of mutations suspected to be associated with PFA resistance were evaluated by site-directed mutagenesis of wild-type or thymidine analogue mutations (TAM)-carrying pNL4-3. Reversion of single mutations......) induced PFA resistance and decreased zidovudine resistance 3-13-fold. These mutants exhibited high-level lamivudine resistance (>20-fold) without mutation M184V. Reversion of K70G --> R and K219R --> E in a patient-derived clone confirmed the contribution of individual mutations and the negative...

  17. Military Suicide Research Consortium

    Science.gov (United States)

    2016-10-01

    participants would be trained to make more neutral discriminations between a highly diluted target stimulus (e.g., gasoline) mixed in a neutral base...Matthew Nock had the following: • Anxiety and Depression Association of America , Keynote Address (Nock). 36 MSRC Annual Report YR6...Balsam, K., & Joiner, T. (in press). Suicidal ideation in transgender people: Gender minority stress and interpersonal theory factors. Journal of

  18. Military Suicide Research Consortium

    Science.gov (United States)

    2013-10-01

    HIV /AIDS, Dr. Gina Signoracci, Denver VAMC, $47,454. o Behaviorally Assessing Suicide Risk, Dr. Sean Barnes, Denver VAMC, $46,328. o Romantic...Joiner, T. (2010). The latent structure of dietary restraint, body dissatisfaction, and drive for thinness: A series of taxometric analyses...Behavior management training for the treatment of Reactive Attachment Disorder. Child Maltreatment, 13, 289-297. 6. Buckner, J., Joiner, T

  19. Tinnitus-Induced Suicide

    Directory of Open Access Journals (Sweden)

    Serhan Derin

    2015-04-01

    Full Text Available Tinnitus is one of the most common complaints in otolaryngology practice. Tinnitus may often be accompanied with hearing loss and vertigo. Tinnitus may impair the quality of life in advanced degrees. In very rare cases, it may cause suicide. In this report, we presented the case of a 61-year-old female patient who attempted suicide due to tinnitus. She suffered from constant tinnitus in both ears since she had undergone serous otitis media two months ago. Despite medical treatment, tinnitus did not improve, and lately, she suffered from severe insomnia. Due to severe tinnitus and insomnia, she drank hydrochloric acid. She was consequently admitted to our emergency department by her family. On physical examination, the patient’s vital signs were stable and floor of the mouth mucosa, gingiva, and hard and soft palate had widely ulcerated areas. Severe laryngeal edema and ulceration was observed on laryngoscopic examination. The eardrum was myringosclerotic on otoscopic examination. The patient was closely followed for respiratory distress; however, tracheostomy was not required. The abovementioned case suggests that patients admitted with complaints of tinnitus should be questioned for severity of depressive symptoms, considering that the presence of depressive symptoms in these patients may result in an attempt of suicide. These patients should be evaluated not only in otolaryngology clinics but also in psychiatric clinics, and subsequently receive appropriate support.

  20. Predictors of Multiple Suicide Attempts among Suicidal Black Adolescents

    Science.gov (United States)

    Merchant, Christopher; Kramer, Anne; Joe, Sean; Venkataraman, Sanjeev; King, Cheryl A.

    2009-01-01

    Psychopathology, social support, and interpersonal orientation were studied in relation to suicide attempt status in acutely suicidal, psychiatrically hospitalized Black adolescents and a matched sample of White adolescents. In the total sample, multiple attempters were differentiated by lower perceived support. Within the Black youth subsample,…

  1. Suicide attempts and suicides in Bolivia from 2007 to 2012

    DEFF Research Database (Denmark)

    Jørs, Erik; Christoffersen, Mette; Veirum, Nikoline Høgsgaard

    2014-01-01

    adults aged 20-29 years, and older adults aged above 29 years. Data from the hospital wards and Crime Statistics were pooled to compare characteristics of suicide attempts with suicides concerning age and gender. Data on age, gender, methods used, and reasons were analyzed using IBM SPSS version 21...

  2. Suicide Inside A Systematic Review of Inpatient Suicides

    NARCIS (Netherlands)

    Bowers, L.; Nijman, H.L.I.; Banda, T.

    2010-01-01

    The literature on inpatient suicides was systematically reviewed. English, German, and Dutch articles were identified by means of the electronic databases PsycInfo, Cochrane, Medline, EMBASE psychiatry, CINAHL, and British Nursing Index. In total, 98 articles covering almost 15,000 suicides were

  3. Cultural correlates of youth suicide.

    Science.gov (United States)

    Eckersley, Richard; Dear, Keith

    2002-12-01

    Youth suicide has risen in most developed nations over the past 50 years, especially among males, but the increase remains to be explained. Statistical analyses were used to examine associations between youth suicide rates in 11-21 mainly Western, developed nations and 32 socio-economic and cultural variables. The central hypothesis was that suicide rates would be correlated with various cultural measures of social attachment and integration, especially individualism. Socio-economic variables were included in the analysis to demonstrate the relative strength of the cultural associations. The study found a strong positive correlation between male youth suicide rates and subjective measures of health, optimism, and several indices of individualism, including personal freedom and control. Correlations between female youth suicide and individualism were smaller, attaining significance in only one instance. Male youth suicide and individualism were negatively correlated with older people's sense of parental duty. Correlations between suicide and other possibly relevant cultural variables--tolerance of suicide, belief in God and national pride--were not significant. The analysis of socio-economic variables yielded only one significant, but doubtful, correlation. The findings can be interpreted as supporting two very different hypotheses: that youth suicide represents "an island of misery in an ocean of happiness" or "the tip of an iceberg of suffering". In favouring the latter interpretation, and consistent with Durkheim's theories on suicide, it is argued that increased youth suicide reflects a failure of Western societies to provide appropriate sites or sources of social identity and attachment, and, conversely, a tendency to promote unrealistic or inappropriate expectations of individual freedom and autonomy.

  4. Suicide Method Runs in Families: A Birth Certificate Cohort Study of Adolescent Suicide in Taiwan

    Science.gov (United States)

    Lu, Tsung-Hsueh; Chang, Wan-Ting; Lin, Jin-Jia; Li, Chung-Yi

    2011-01-01

    Suicide method used by adolescents was examined to determine if it was the same as that employed by their suicidal parents. Six hundred eighty adolescents completed suicide between 1997 and 2007, of whom 12 had parents who had previously died by suicide. The suicide method used by these adolescents was compared with that employed by their suicidal…

  5. Pathways for Preparation: Locating Suicide Education in Preparing Professionals for Encounters with Suicidal Adolescents

    Science.gov (United States)

    Ranahan, Patti

    2013-01-01

    Current suicide prevention strategies often include suicide education based on the premise that education can lead to recognition of those at risk of suicide and others who are prepared can respond and potentially save lives. As suicide is a leading cause of death for young people, it is relevant to explore how suicide education is made available…

  6. Attempted suicide and completed suicide among young people

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The study explore risk factors associated with the onset of suicidal behavior in young people aged 15 to 24. The study survey possible risk factors and protective factors in order to evaluate if altering the conditions of children’s upbringing, structural factors, geographical segregation......, or individual resource deficits could reduce their suicidal behavior (first time suicide attempts and completed suicides). These issues are being examined using data gathered during a 10-year longitudinal study of two births cohorts of more than 145,000 young people born in 1966 or 1980. In the Nordic welfare...... model it is an ambition to level-out inequalities and give children the same opportunities despite parental income or educational resources. The paper focuses on suicidal behavior as an extreme indicator of individual disadvantage and social disintegration in order to disentangle groups of risk factors...

  7. Interventions to reduce suicides at suicide hotspots: a systematic review.

    Science.gov (United States)

    Cox, Georgina R; Owens, Christabel; Robinson, Jo; Nicholas, Angela; Lockley, Anne; Williamson, Michelle; Cheung, Yee Tak Derek; Pirkis, Jane

    2013-03-09

    'Suicide hotspots' include tall structures (for example, bridges and cliffs), railway tracks, and isolated locations (for example, rural car parks) which offer direct means for suicide or seclusion that prevents intervention. We searched Medline for studies that could inform the following question: 'What interventions are available to reduce suicides at hotspots, and are they effective?' There are four main approaches: (a) restricting access to means (through installation of physical barriers); (b) encouraging help-seeking (by placement of signs and telephones); (c) increasing the likelihood of intervention by a third party (through surveillance and staff training); and (d) encouraging responsible media reporting of suicide (through guidelines for journalists). There is relatively strong evidence that reducing access to means can avert suicides at hotspots without substitution effects. The evidence is weaker for the other approaches, although they show promise. More well-designed intervention studies are needed to strengthen this evidence base.

  8. Suicide risk factors and mediators between childhood sexual abuse and suicide ideation among male and female suicide attempters.

    Science.gov (United States)

    Spokas, Megan; Wenzel, Amy; Stirman, Shannon Wiltsey; Brown, Gregory K; Beck, Aaron T

    2009-10-01

    The current study examined the manner in which childhood sexual abuse (CSA) history relates to risk factors for suicidal behavior among recent suicide attempters (n = 166). Men who recently attempted suicide and endorsed a CSA history had higher scores on measures of hopelessness and suicide ideation than men without a CSA history. Men with a CSA history were also more likely to have made multiple suicide attempts and meet diagnostic criteria for posttraumatic stress disorder and borderline personality disorder. In contrast, there were fewer group differences as a function of CSA history among the female suicide attempters. Hopelessness was a significant mediator between CSA history and suicide ideation in both men and women.

  9. The Teen Suicide Research Project.

    Science.gov (United States)

    Paulson, Barbara L.; Everall, Robin D.

    2001-01-01

    Reports preliminary findings from ongoing interviews with youth who had experienced suicidal thoughts or behaviors. Suicide risk was associated with negative life events or extreme difficulty in school, overwhelming daily stresses, and absence of support. Teachers had a huge impact on the psychological functioning of troubled adolescents. (SV)

  10. Suicide risk among homeless population

    Directory of Open Access Journals (Sweden)

    Fran Calvo-García

    2016-06-01

    Full Text Available There exists little scientific production on autolytic behaviour in homeless people, despite the fact that it is one of the groups that is more at risk. The aim of this study is to determine the prevalence of previous attempted suicide and suicide risk and its connection with the main risk factors. In order to do so, central tendency and dispersion measures, correlations, contingence tables, and average comparison tables according to type of variable and normality were used. The Plutchik suicide-risk test was used in order to determine the risk of suicide, and specific tests for the main risk factors analysed. The main results show a 24.7% suicide rate and 45.2% (n = 66 displayed suicide risk. The main predictive factor of the risk of suicide was the daily consumption of alcohol (OR = 1.011, p less than .001, followed by being a woman (OR = 1.381, p = .021. It is necessary to design and apply suicide prevention strategies for this population.

  11. Death Education and Suicide Potentiality.

    Science.gov (United States)

    Rosenthal, Nina Ribak

    1983-01-01

    Assessed whether a death education course attracted students with significantly different attitudes toward death. Results indicated that the death education class did attract persons with greater acceptance of suicide and death. The course tended to further decrease avoidance and increase acceptance. Potentiality for committing suicide was not…

  12. Latina Teen Suicide and Bullying

    Science.gov (United States)

    Romero, Andrea J.; Wiggs, Christine Bracamonte; Valencia, Celina; Bauman, Sheri

    2013-01-01

    Latina adolescents experience depression and suicidal ideations in a disproportionate manner compared to their non-Latina counterparts. We investigate suicide and depressive symptoms among a state-wide sample (N = 650) of adolescent Latina girls with a focus on bullying as a predictor. Bullying rates are higher than previous studies have found for…

  13. Cannabis use and suicidal ideation

    NARCIS (Netherlands)

    van Ours, J.C.; Williams, J.; Fergusson, D.; Horwood, L.J.

    2013-01-01

    Globally, suicide has emerged as the second leading cause of death among youth aged 10–24 years old. In order to better understand the causes of this phenomenon, we investigate the relationship between suicidal ideation and cannabis use. Our empirical analysis is based on a 30-year longitudinal

  14. Suicide in Guyana: Nurses' Perspectives.

    Science.gov (United States)

    Anthony, Maureen; Groh, Carla; Gash, Jean

    Guyana, an English-speaking country on the north coast of South America, has the highest suicide rate in the world. Nurses are an integral part of the healthcare team working with patients experiencing psychological distress and are uniquely qualified to add to the discourse on factors contributing to the high suicide rate in Guyana. The purpose of this study was to explore the attitudes and experiences of nurses and nurse assistants in Guyana related to suicide. Nine registered nurses and nurse assistants who worked at a private hospital in Georgetown, Guyana, were recruited to participate in a focus group. The focus group lasted approximately 70 minutes and was recorded. The audio recordings were later transcribed word for word. Four themes emerged from the data: family issues as they relate to the high suicide rate, suicide attempts as a cry for help, lack of support, and coping mechanisms used by nurses when caring for victims of attempted suicide. Nurses are uniquely positioned to intervene with families in crisis, whether it be suicide, suicide attempts, or the underlying factors of family dysfunction, child maltreatment, poverty, or alcoholism. Establishing forensic nursing as a specialty in Guyana would validate this important role through education and certification of nurses.

  15. Toward a Biosignature for Suicide

    Science.gov (United States)

    Oquendo, Maria A.; Sullivan, Gregory M.; Sudol, Katherin; Baca-Garcia, Enrique; Stanley, Barbara H.; Sublette, M. Elizabeth; Mann, J. John

    2015-01-01

    Objective Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. Method The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. Results Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. Conclusions The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors. PMID:25263730

  16. Cannabis and suicide: longitudinal study.

    Science.gov (United States)

    Price, Ceri; Hemmingsson, Tomas; Lewis, Glyn; Zammit, Stanley; Allebeck, Peter

    2009-12-01

    Some studies suggest that cannabis use is associated with suicidal ideation, but no detailed longitudinal study has examined suicide as an outcome. To examine the association between cannabis use and completed suicide. A longitudinal study investigated 50 087 men conscripted for Swedish military service, with cannabis use measured non-anonymously at conscription. Suicides during 33 years of follow-up were identified by linkage with the National Cause of Death Register. There were 600 (1.2% of cohort) suicides or deaths from undetermined causes. Cannabis use was associated with an increased risk of suicide (crude OR for 'ever use' 1.62, 95% CI 1.28-2.07), but this association was eliminated after adjustment for confounding (adjusted OR = 0.88, 95% CI 0.65-1.20). Although there was a strong association between cannabis use and suicide, this was explained by markers of psychological and behavioural problems. These results suggest that cannabis use is unlikely to have a strong effect on risk of completed suicide, either directly or as a consequence of mental health problems secondary to its use.

  17. Impaired Decision Making in Adolescent Suicide Attempters

    Science.gov (United States)

    Bridge, Jeffrey A.; McBee-Strayer, Sandra M.; Cannon, Elizabeth A.; Sheftall, Arielle H.; Reynolds, Brady; Campo, John V.; Pajer, Kathleen A.; Barbe, Remy P.; Brent, David A.

    2012-01-01

    Objective: Decision-making deficits have been linked to suicidal behavior in adults. However, it remains unclear whether impaired decision making plays a role in the etiopathogenesis of youth suicidal behavior. The purpose of this study was to examine decision-making processes in adolescent suicide attempters and never-suicidal comparison…

  18. Suicide and Its Prevention on College Campuses

    Science.gov (United States)

    Keyes, Lee

    2012-01-01

    Suicide is a significant issue facing higher education institutions. Many campuses are involved in a variety of procedures, programs, and initiatives that seek to reduce or prevent suicide and the impact of suicide-related behavior. This article offers examples of campus prevention efforts, important resources on suicide prevention for college…

  19. SUICIDE AMONG UNIVERSITY STUDENTS IN KENYA: CAUSES ...

    African Journals Online (AJOL)

    Suicide is against the law in Kenya. The existence of suicide phenomena in the society is a major issue that needs to be looked into with a lot of concern, and creating effective preventative measure is a matter of urgency. Knowledge concerning suicide is largely limited. The majority of people in the society treat suicide ...

  20. Grief Experiences and Expectance of Suicide

    NARCIS (Netherlands)

    Wojtkowiak, J.; Wild, V.; Egger, J.I.M.

    2012-01-01

    Suicide is generally viewed as an unexpected cause of death. However, some suicides might be expected to a certain extent, which needs to be further studied. The relationships between expecting suicide, feeling understanding for the suicide, and later grief experiences were explored. In total, 142

  1. Situational Analysis of Attitudes toward Suicide Behavior.

    Science.gov (United States)

    Ingram, Ellen; Ellis, Jon B.

    1995-01-01

    College students (n=228) completed a suicide ideation questionnaire and read one of 4 scenarios: cancer, AIDS, schizophrenia, and depression. People in the cancer and AIDS scenario were viewed as the most justified in committing suicide. Suicide ideators saw the people in the scenarios as justified in committing suicide more often than did…

  2. Grief Experiences and Expectance of Suicide

    Science.gov (United States)

    Wojtkowiak, Joanna; Wild, Verena; Egger, Jos

    2012-01-01

    Suicide is generally viewed as an unexpected cause of death. However, some suicides might be expected to a certain extent, which needs to be further studied. The relationships between expecting suicide, feeling understanding for the suicide, and later grief experiences were explored. In total, 142 bereaved participants completed the Grief…

  3. Moody, Suicide and Survival: A Critical Appraisal.

    Science.gov (United States)

    Vicchio, Stephen

    1980-01-01

    The purpose of this paper is to: (1) define suicide; (2) explicate Raymond Moody's position on suicide and survival after death; (3) analyze logical connections between divine commands and moral judgments; and (4) offer constructive comments on suicide and suicide prevention. (Author/RC)

  4. Last Suicide Attempt before Completed Suicide in Severe Depression: An Extended Suicidal Process May Be Found in Men Rather Than Women.

    OpenAIRE

    Brådvik, Louise

    2013-01-01

    The objective of this study was to compare the time from last suicide attempt to suicide in men and women with major depressive disorder with melancholic and/or psychotic features. The case records of 100 suicide victims with severe depression were evaluated. All suicide attempts during the course of depression were noted. The time from last suicide attempt to suicide was compared as well as the occurrence of suicide attempt during the last depressive episode, by gender. Male suicide attempte...

  5. Pyruvate kinase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

  6. Malignant diseases as suicidal motives

    Directory of Open Access Journals (Sweden)

    Bogdanović Ljiljana

    2007-01-01

    Full Text Available Introduction Suicide is a conscious and intentional destruction of one’s own life, which occurs as a result of mutual influence of a person’s disposition and motives (facts inspiring the commitment of suicide. It is well known that various diseases, including malignancies, could be important and in some cases the only motive for committing suicide. Objective The purpose of the study was to analyze in detail suicides of persons whose only motive was an established malignant disease. Method The analysis was performed using the autopsy material of the Institute of Forensic Medicine, School of Medicine, University of Belgrade, during the period from 1990 to 2004. The reports on performed medico-legal autopsies were used, as well as history data obtained from the family members of suicidal persons, investigation reports and the available medical documents. Results In 1931 cases there was established suicidal nature of a violent death. Neoplasms were the suicidal motive in 37 persons (1.9%. The basic characteristics of the analyzed sample were predominance of males (26:11, ratio 2.4:1, the age of over 70 years and the highest incidence of malignant lung and breast tumors. Almost all cases were the persons who underwent treatment for malignant neoplasms over a longer period of time. During 19 autopsies (51.3% out of 37, a progressive phase of malignancy was established, i.e. metastases. The data on prior oral announcement of suicide intention were obtained for 70.3% (26 cases, and on previous suicidal attempts only for 13.5% (5 cases. In the majority of cases (78.4% the place of committed suicide was the person’s home. In 16 cases (43.2% the suicide was committed with a firearm. Hanging as a manner of destroying one’s own life was chosen by 12 persons (32.4%, while other ways were less frequently used. Conclusion Although malignancies were not present with high incidence as a suicidal motive in our analyzed sample, such cases require particular

  7. Suicide Risk Factors and Mediators between Childhood Sexual Abuse and Suicide Ideation Among Male and Female Suicide Attempters

    OpenAIRE

    Spokas, Megan; Wenzel, Amy; Stirman, Shannon Wiltsey; Brown, Gregory K.; Beck, Aaron T.

    2009-01-01

    The current study examined the manner in which childhood sexual abuse (CSA) history relates to risk factors for suicidal behavior among recent suicide attempters (n = 166). Men who recently attempted suicide and endorsed a CSA history had higher scores on measures of hopelessness and suicide ideation than men without a CSA history. Men with a CSA history were also more likely to have made multiple suicide attempts and meet diagnostic criteria for posttraumatic stress disorder and borderline p...

  8. Actions of exogenous histones and other proteins on [3H]-thymidine incorporation into DNA of Novikoff hepatoma cells

    International Nuclear Information System (INIS)

    Barra, R.; Beres, B.; Koch, M.R.; Lea, M.A.

    1976-01-01

    The effects of exogenous proteins on the incorporation of [ 3 H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A 2 , 5123C and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10 to 20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100 to 400μg/ml. In experiments with lower cell concentrations, a 60% or greater increase in [ 3 H]-thymidine incorporation could be obtained with total calf thymus histone and with Fl and arginine-rich histones from rat liver. At concentrations of 1 to 2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80 to 90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10μg/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis. (author)

  9. Books reconsidered: Emile Durkheim, Le Suicide.

    Science.gov (United States)

    Robertson, Michael

    2006-12-01

    To reappraise Emile Durkheim's taxonomy of suicide in Le Suicide in the light of recent experience. While Durkheim's scientific method and argument are fundamentally flawed, some of his concepts have instrumental value in attempting to understand the complex origins of suicidal behaviour. Durkheim's baseless dismissal of mental illness as a key determinant of suicidal behaviour weakens his thesis significantly. However, his conceptualization of anomic, egoistic and altruistic suicide provides a means of comprehending recent trends in suicidal behaviour in the former Soviet states and a possible window into the psyche of the suicides of religious and political extremists.

  10. Precise site-selective termination of DNA replication by caging the 3-position of thymidine and its application to polymerase chain reaction.

    Science.gov (United States)

    Kuzuya, Akinori; Okada, Fuminori; Komiyama, Makoto

    2009-10-21

    A new caged thymidine, 3-N-(2-(2-nitrophenyl)propyloxymethyl)thymidine (T(NPPOM)) was synthesized and used as a site-selective terminator of DNA-polymerase reaction in light-assisted cohesive-ending PCR (LACE-PCR), which directly gives sticky-ended PCR products after brief UVA irradiation. Primer-extension experiments using a template involving T(NPPOM) have shown that this caged nucleotide efficiently and site-selectively blocks reactions of a variety of polymerases commonly used in PCR. Misincorporation of nucleobases, observed with the use of other previously reported caged thymidines, scarcely occurred. It has turned out that a slight structural difference of caging groups can significantly improve the termination yield of polymerase reactions. A LACE-PCR product coding GFP gene was prepared by using primers containing T(NPPOM) and was ligated with a vector fragment prepared using restriction enzymes. The resulting recombinant vector successfully transformed E. coli.

  11. Suicide in Obsessive Compulsive and Related Disorders

    Directory of Open Access Journals (Sweden)

    Gonca Karakus

    2015-09-01

    Full Text Available Suicide is a complex term. Suicide attempts are common in women, but completed suicide rates are higher in men. Several demographic factors, stressful life events, previous suicide attempts, childhood abuse, physical or psychiatric disorders are risk factors for suicide. Suicide rates in a variety of mental disorders is more than the normal population. Data on rates and risk factors of suicide in patients with obsessive-compulsive disorder and related disorders are limited. Present data are often associated with patients with obsessive compulsive disorder and body dysmorphic disorder. Lifetime suicidal ideation rates in patients with obsessive compulsive disorder is within a range of 36-63%. Any comorbid psychiatric diagnosis is an important risk factor for suicide in this disorder. This article aims to review the relationship between suicide and obsessive compulsive and related disorders [Archives Medical Review Journal 2015; 24(3.000: 402-413

  12. Military and civilian media coverage of suicide.

    Science.gov (United States)

    Edwards-Stewart, Amanda; Kinn, Julie T; June, Jennifer D; Fullerton, Nicole R

    2011-01-01

    Military suicide has increased over the past decade and reports of Service Member and Veteran suicides receive media attention. Some methods of reporting suicide appear to cause a "media contagion" effect, potentially increasing suicide. This effect is explored in relation to media reports of both military and civilian suicides. To reduce possible contagion, recommendations for media reporting of suicides were adapted by the Suicide Prevention Resource Center (SPRC). We assessed 240 military and civilian newspaper reports of suicide from 15 different sources for compliance with the SPRC guidelines. Nearly all reviewed articles violated at least one guideline. Results highlighted military news articles regarding Service Members included more pejorative language and discussion of failed psychological treatment. Conversely, civilian articles romanticized the victim and provided more details regarding the suicide. Further exploration of military suicide reporting bias is discussed as a need in future research.

  13. Religion and Suicide Risk: A Systematic Review.

    Science.gov (United States)

    Lawrence, Ryan E; Oquendo, Maria A; Stanley, Barbara

    2016-01-01

    Although religion is reported to be protective against suicide, the empirical evidence is inconsistent. Research is complicated by the fact that there are many dimensions to religion (affiliation, participation, doctrine) and suicide (ideation, attempt, completion). We systematically reviewed the literature on religion and suicide over the last 10 years (89 articles) with a goal of identifying what specific dimensions of religion are associated with specific aspects of suicide. We found that religious affiliation does not necessarily protect against suicidal ideation, but does protect against suicide attempts. Whether religious affiliation protects against suicide attempts may depend on the culture-specific implications of affiliating with a particular religion, since minority religious groups can feel socially isolated. After adjusting for social support measures, religious service attendance is not especially protective against suicidal ideation, but does protect against suicide attempts, and possibly protects against suicide. Future qualitative studies might further clarify these associations.

  14. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    OpenAIRE

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

    2015-01-01

    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  15. Essential Questions on Suicide Bereavement and Postvention

    OpenAIRE

    Andriessen, Karl; Krysinska, Karolina

    2011-01-01

    During the past decades public and research interest in postvention, i.e., support for families and communities after a suicide, has increased. However, the postvention field is still facing a number of important challenges and questions. This article aims to discuss a series of essential issues on suicide bereavement and postvention, regarding the current state of the art and future developments. Who is a suicide survivor and how many suicide survivors are there? Is suicide bereavement diffe...

  16. Suicide Research and Adolescent Suicide Trends in New Zealand

    Directory of Open Access Journals (Sweden)

    Said Shahtahmasebi

    2008-01-01

    Full Text Available In recent years, there have been a number of claims and counterclaims from suicide research using time series and longitudinal data; in particular, the linkage of increased antidepressant prescriptions to a decrease in suicide rates. Suicide time series appear to have a memory compounded with seasonal and cyclic effects. Failure to take into account these properties may lead to misleading conclusions, e.g., a downward blip is interpreted as the result of current knowledge and public health policies, while an upward blip is explained as suicide being complex depending on many variables requiring further research. In previous publications, I argued that this misuse of time series data is the result of an uncritical acceptance of a medical model that links mental ill-health to suicide. The consequences of such research behaviour are further increases in antidepressant prescriptions and medications to those who should not be prescribed them, with adverse effects showing across the population, e.g., the prescription of antidepressants to very young children (some under 1 year of age in New Zealand. Moreover, the New Zealand Evidence-based Health Care Bulletin recommends an authoritarian approach for every interaction with a young person to check their psychosocial well-being. When viewed holistically, this kind of human behaviour makes researchers, policy makers (politicians, treatment, and practitioners, and society in general part of the problem rather than the solution. This paper explores some dynamic aspects of suicide, using only official data with particular reference to youth suicide, and suggests that the medical model of suicide is only an attempt to treat depression without addressing suicide, and recommends the creation of a unified database through understanding the society that individuals live in. It is hoped that this paper will stimulate debate and the collaboration of international experts regardless of their school of thought.

  17. Assisted suicide and euthanasia.

    Science.gov (United States)

    van der Heide, Agnes

    2013-01-01

    Several countries have adopted laws that regulate physician assistance in dying. Such assistance may consist of providing a patient with a prescription of lethal medication that is self-administered by the patient, which is usually referred to as (physician) assistance in suicide, or of administering lethal medication to a patient, which is referred to as euthanasia. The main aim of regulating physician assistance in dying is to bring these practices into the open and to provide physicians with legal certainty. A key condition in all jurisdictions that have regulated either assistance in suicide or euthanasia is that physicians are only allowed to engage in these acts upon the explicit and voluntary request of the patient. All systems that allow physician assistance in dying have also in some way included the notion that physician assistance in dying is only accepted when it is the only means to address severe suffering from an incurable medical condition. Arguments against the legal regulation of physician assistance in dying include principled arguments, such as the wrongness of hastening death, and arguments that emphasize the negative consequences of allowing physician assistance in dying, such as a devaluation of the lives of older people, or people with chronic disease or disabilities. Opinion polls show that some form of accepting and regulating euthanasia and physician assistance in suicide is increasingly supported by the general population in most western countries. Studies in countries where physician assistance in dying is regulated suggest that practices have remained rather stable in most jurisdictions and that physicians adhere to the legal criteria in the vast majority of cases. © 2013 Elsevier B.V. All rights reserved.

  18. Suicidal Ideation and Distress in Family Members Bereaved by Suicide in Portugal

    OpenAIRE

    Santos, Sara; Campos, Rui C.; Tavares, Sofia

    2015-01-01

    The present study assessed the impact of suicide and distress on suicidal ideation in a sample of 93 Portuguese family members bereaved by suicide. A control community sample of 102 adults also participated. After controlling for educational level, those bereaved by the suicide of a family member were found to have higher levels of suicidal ideation. Forty-two percent of family members had Suicide Ideation Questionnaire scores at or above the cutoff point. General distress, dep...

  19. Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation.

    Science.gov (United States)

    Belot, Marie-Pierre; Abdennebi-Najar, Latifa; Gaudin, Françoise; Emilie, Dominique; Machelon, Véronique

    2007-12-01

    Mast cells proliferate in vivo in areas of active fibrosis, during parasite infestations, in response to repeated immediate hypersensitivity reactions and in patients with mastocytosis. We investigated how progesterone reduces the proliferation of HMC-1(560) mast cells that proliferate spontaneously in culture. Cells were incubated with 1 microM to 1 nM progesterone for 24-48 h. Progesterone (1 microM) reduced the spontaneous proliferation of HMC-1(560) mast cells to half that of cells cultured without hormone. [(3)H] thymidine incorporation was only 50% of control; there were fewer cells in G2/M and more cells in G0/G1. The amounts of phospho-Raf-1 (Tyr 340-341) and phospho-p42/p44 MAPK proteins were also reduced. In contrast progesterone had no effect on MAP kinase-phosphatase-1. The Raf/MAPK pathway, which depends on Src kinase activity, is implicated in the control of cell proliferation. HMC-1(560) cells incubated with the tyrosine kinase inhibitor PP1 proliferated more slowly than controls and had less phospho-Raf-1 (Tyr 340-341) and phospho-p42/p44 MAPK. The Csk homologous kinase (CHK), an endogenous inhibitor of Src protein tyrosine kinases, was also enhanced in progesterone-treated cells. In contrast, progesterone had no effect on the growth of cells transfected with siRNA CHK. We conclude that progesterone increases the amount of csk homologous kinase, which in turn reduces HMC-1(560) mast cell proliferation. This effect parallels decreases in the phosphorylated forms of Raf-1 and p42/44 MAPK, as their production depends on Src kinase activity. (c) 2007 Wiley-Liss, Inc.

  20. Consequences of chemoresistance for the herpes simplex virus thymidine kinase/ganciclovir-induced bystander effect in a human small cell lung cancer cell line model

    NARCIS (Netherlands)

    Van Dillen, IJ; Mulder, NH; Sluiter, WJ; Meijer, C; De Jong, S; Loncarek, J; Mesnil, M; De Vries, EFJ; Vaalburg, W; Hospers, GAP

    2005-01-01

    This paper focuses on the influence of chemoresistance on the herpes simplex virus (HSVtk)/ganciclovir (GCV)-induced bystander effect (BE), as studied in a human small cell lung cancer (SCLC) cell line (GLC(4)) and its sublines with in vitro acquired resistance to adriamycin (GLC(4)/ADR),

  1. Suicidal behavior in Indian adolescents.

    Science.gov (United States)

    Samuel, Diana; Sher, Leo

    2013-01-01

    Suicide is both a public and mental health problem, and is a leading cause of deaths, especially among adolescents. Two factors that contribute to the decision of adolescents to commit suicide are having a primary mood disorder and/or substance use. In the Indian culture, the family unit has both a positive and negative impact on suicide. The family serves as a protective factor that provides a strong support for the individual, but alternately creates an inseparable individual when seeking mental health care, which often complicates the situation. Due to the stigma, Indians typically perceive having a mental illness as shameful. Religion is integral to the Indian culture so much so that individuals often use herbal remedies, seek help from religious leaders, and attend religious establishments prior to obtaining a mental health evaluation in those that are subsequently deemed as mentally ill. Despite the fact that suicides are underreported and misdiagnosed in India, it is known that the highest rates are among those immigrating, Indians tend to switch the methods they use to commit suicide from ingestion of poison to hanging, which may reflect a lack of available poisonous substances or the influence of the host culture. Considering the high suicide rates in adolescents, the importance of providing psychoeducation, restricting access to lethal means, and promoting social integration in immigrants are various ways by which suicides in Indian adolescents can be avoided.

  2. Internet Forums for Suicide Bereavement.

    Science.gov (United States)

    Bailey, Eleanor; Krysinska, Karolina; O'Dea, Bridianne; Robinson, Jo

    2017-11-01

    Bereavement by suicide is associated with a number of consequences including poor mental health outcomes and increased suicide risk. Despite this, the bereaved by suicide may be reluctant to seek help from friends, family, and professionals. Internet forums and social networking sites are a popular avenue of support for the bereaved, but to date there is a lack of research into their use and efficacy. To survey users of suicide bereavement Internet forums and Facebook groups regarding their help-seeking behaviors, use of forums, and perceived benefits and limitations of such use. This study employed a cross-sectional design in which users of suicide bereavement Internet forums and Facebook groups completed an anonymous online survey. Participants were 222 users of suicide bereavement Internet forums. Most participants (93.2%) had sought face-to-face help from sources other than Internet forums, but were more likely to seek help in the near future from informal rather than formal sources. Forums were perceived as highly beneficial and there were few limitations. The generalizability of these results to other internet forums may be limited. Additionally, we were not able to examine differences between forums in terms of quality or user-reported efficacy. Finally, the data reflects the subjective views of forum users, which may differ from the views of moderators or experts. Internet forums, including Facebook groups, appear to be a useful adjunct to face-to-face help-seeking for supporting those who have been bereaved by suicide.

  3. Suicide prevention through means restriction

    DEFF Research Database (Denmark)

    Knipe, Duleeka W.; Chang, Shu-Sen; Dawson, Andrew

    2017-01-01

    Objective: To investigate the effect of 3-year phased bans of the pesticides dimethoate and fenthion in 2008–2010, and paraquat in 2009–2011, on suicide mortality in Sri Lanka. Methods: Age-standardised overall, sex-specific, and method-specific suicide rates were calculated using Sri Lankan police...... data (1989–2015). Using negative binomial regression models, we estimated the change in the rate and number of suicide deaths in post-ban years (2011–15) compared to those expected based on pre-ban trends (2001–10). Findings: Overall suicide mortality dropped by 21% between 2011 and 2015, from 18.......3 to 14.3 per 100,000. The decline in pesticide suicides during this same period was larger than for overall suicides: from 8.5 to 4.2 per 100,000, a 50% reduction. This was accompanied by a smaller concurrent rise in non-pesticide suicide mortality with a 2% increase (9.9 to 10.1 per 100,000). In 2015...

  4. Associations of Tabloid Newspaper Use With Endorsement of Suicide Myths, Suicide-Related Knowledge, and Stigmatizing Attitudes Toward Suicidal Individuals.

    Science.gov (United States)

    Till, Benedikt; Wild, Teresa A; Arendt, Florian; Scherr, Sebastian; Niederkrotenthaler, Thomas

    2018-04-05

    Educating the public about suicide is an important component of suicide prevention. So far, little is known about whether common misconceptions of suicide are related to individual tabloid newspaper use. This study aimed to investigate associations of time spent reading tabloids with endorsement of suicide myths, suicide-related knowledge, and with stigmatizing attitudes toward suicidal individuals. In this cross-sectional online survey, we assessed suicide-related knowledge and stigmatizing attitudes toward suicidal individuals among 456 study participants in Austria together with their endorsement of five common suicide myths (e.g., "suicidal individuals do not communicate their intent"). Furthermore, we assessed participants' time spent reading tabloids. Multivariate analyses controlling for gender, age, education, and the time spent reading broadsheet newspapers and watching television indicated that participants' time spent reading tabloids was associated with higher endorsement of suicide myths as well as with a lower level of suicide-related knowledge and a higher level of stigmatizing attitudes toward suicidal individuals. Due to the study's cross-sectional design, causality concerning these associations could not be assessed. The present findings confirm that readers of tabloids are an important target group for suicide education efforts.

  5. Suicidality in the "prodromal" phase of schizophrenia.

    Science.gov (United States)

    Andriopoulos, Ioannis; Ellul, John; Skokou, Maria; Beratis, Stavroula

    2011-01-01

    Patients with schizophrenia are at high risk for suicide ideation, attempts, and completed suicide. However, suicidal behavior during the prodromal phase of schizophrenia and a possible association between prodromal suicidal behavior and suicidality after the onset of overt psychosis are not studied. One hundred six consecutively admitted schizophrenia patients with recent onset were evaluated retrospectively for prodromal symptoms and suicidality during the prodromal phase and after the onset of frank psychosis. In addition, 106 matched control subjects from the general population were evaluated for suicidality during the same age period of the prodromal phase of the corresponding patient. Suicide ideation and attempt during the prodromal period were reported in 25.5% and 7.5% of the patients, which are 3.8- and 8-fold greater than in the controls, respectively. Patients with suicidal behavior experienced a greater number of prodromal symptoms than those without. Prodromal depressive mood, marked impairment in role functioning, and tobacco smoking exerted an independent effect on suicide ideation, whereas depressive mood was the symptom significantly more frequent in patients with suicide attempt. Suicide attempts were associated with an earlier onset of prodromal symptoms and frank psychosis. All patients with prodromal suicide attempts were cigarette smokers. Suicide ideation during the prodromal phase was strongly associated with lifetime suicidality after the onset of frank psychosis. Suicidal behavior is quite common during the prodromal period. The association of smoking, depressive mood, impaired functioning, and a large number of prodromal symptoms, particularly in patients with an early onset of symptomatology, carries a substantially increased risk for suicide ideation. Particular care is needed in patients with prodromal suicide ideation after the onset of frank psychosis because the risk to attempt suicide is high. Copyright © 2011 Elsevier Inc. All

  6. 3H thymidine an indicator of benzo(a)pyrene induced lung carcinogenesis: role of quercetin and curcumin

    International Nuclear Information System (INIS)

    Nair, Parveen; Malhotra, A.; Dhawan, D.K.

    2010-01-01

    Full text: Lung cancer is responsible for most of the cancer related deaths and calls for new approaches to control the menace. In the present study chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP) induced lung carcinogenesis. The mice were segregated into five groups which included normal control, BP treated, BP+curcumin treated, BP+quercetin treated and BP+curcumin+quercetin treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis, after 22 weeks of single i.p. injection of BP at a dose of 100 mg/Kg body weight to mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75, respectively in the BP treated mice. A statistically significant increase in the uptake of 3 H thymidine indicative of increased DNA synthesis which in turn is the marker of uncontrolled cancer cell proliferation, was observed in the lung slices of BP treated mice. Further, BP treatment resulted in marked disruption in the histoarchitecture of lungs. Nuclei were enlarged, thickening of epithelium was seen. Structure-less masses of cells were visible all over. Nuclear pleomorphism and decreased cytoplasmic contents were also observed in BP treated mice. Squamous epithelial metaplasia, severe epithelial thickening and alveolar vocuolizations in distal airways indicative of lung carcinogensis were also observed in the BP treated mice. Supplementation with curcumin alone resulted in a significant decrease in the tumor incidence as well as tumor multicity which were observed to be 77% and 1.42 respectively. Also, quercetin significantly decreased tumor incidence and tumor multiplicity to 70% and 1.28 respectively. However, upon combined supplementation with phytochemicals, an appreciable decrease in the tumor incidence and multiplicity was observed which was found to be 60% and 1.00 respectively. Further, Supplementation with curcumin alone to BP treated mice resulted in statistically

  7. Suicide with 137 cesium

    International Nuclear Information System (INIS)

    Vasileva, B.

    1976-01-01

    A case report is presented of suicide by radiation exposure after a preceding attempt with potassium ferrocyanide. The subject, a 30-year-old nondestructive-testing technician, held with his right fingers and then placed in his left shirt pocket a metal-canned 5,3-Ci 137 Cs source. Despite appearance of signs of severe topical injury by day 3 after the incident and development of systemic toxicity symptoms with indications of affection of internal organs by day 16, medical aid was not sought until day 21 when efforts at management proved unable to prevent fatal outcome. A prominent distinguishing characteristic of this mode of suicide is that the deed's sequelae are delayed in coming into effect. Cases known to have occurred are extremely rare (only two have been described in the literature). This is likely to be related to a distinct unpopularity of radioactive materials as well as their limited availability to the general public. The subjects that did use them were radiation workers having access to such substances; being acquainted with the biological effects of radiation, they, nevertheless, have chosen this protracted and distressful way of taking their lives. (A.B.)

  8. Depressed suicide attempters with posttraumatic stress disorder.

    Science.gov (United States)

    Ramberg, Maria; Stanley, Barbara; Ystgaard, Mette; Mehlum, Lars

    2015-01-01

    Posttraumatic stress disorder and major depressive disorder are well-established risk factors for suicidal behavior. This study compared depressed suicide attempters with and without comorbid posttraumatic stress disorder with respect to additional diagnoses, global functioning, depressive symptoms, substance abuse, history of traumatic exposure, and suicidal behavior. Adult patients consecutively admitted to a general hospital after a suicide attempt were interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four patients (71%) were diagnosed with depression; of them, 21 patients (32%) had posttraumatic stress disorder. There were no group differences in social adjustment, depressive symptoms, or suicidal intent. However, the group with comorbid depression and posttraumatic stress disorder had more additional Axis I diagnoses, a higher degree of childhood trauma exposure, and more often reported previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives. These findings underline the clinical importance of diagnosis and treatment of posttraumatic stress disorder in suicide attempters.

  9. Suicidal ideation in inpatients with acute schizophrenia.

    Science.gov (United States)

    Kontaxakis, Vassilis; Havaki-Kontaxaki, Beata; Margariti, Maria; Stamouli, Sophia; Kollias, Costas; Christodoulou, George

    2004-07-01

    Schizophrenia has been associated with a high rate of suicide. This study investigates the prevalence of suicidal ideation in a population of inpatients with acute schizophrenia, together with the clinical parameters associated with suicidal thoughts. We assessed 93 schizophrenia patients. We matched subjects for age and sex and compared subjects with and without suicidal thoughts. We performed stepwise multiple regression analysis to assess the association between specific clinical symptoms and suicidal ideation. Of the patients, 20.4% reported suicidal thoughts during the last 15 days. Severity of depressive symptoms, motor retardation, guilt feelings, pathological guilt, and self-depreciation predicted the patients' suicidal ideation. Suicidal thoughts are frequent among inpatients with acute schizophrenia. Prevention of suicidal behaviour should include helping patients improve their self-esteem and reducing depression and guilt feelings.

  10. Nursing students’ attitude toward suicide prevention

    Science.gov (United States)

    Nebhinani, Naresh; Mamta; Gaikwad, Achla D.; Tamphasana, L.

    2013-01-01

    Background: Preventing suicide depends upon different health professionals’ knowledge regarding suicide, attitude toward suicide attempters, skills to assess and manage suicidal risk. Objectives: This study was aimed to assess the attitude of nursing students toward suicide prevention. Materials and Methods: 308 nursing students were recruited from the two institutions through total enumeration method. Attitude toward suicide prevention scale was administered. Study design was cross-sectional. Results: Majority were single females, from urban locality, who were pursuing BSc Nursing with the mean age of 20 years. Only minority had previous exposure to suicide prevention programs or workshops. Nearly half of the subjects had positive attitude toward working with suicidal patients. Again half of the subjects considered unemployment and poverty as main causes of suicide and were quite hopeless about it and they also perceived that most of the suicidal people would not reveal their suicidal plans to others. Conclusions: Merely half of the students had positive attitude toward working with suicidal patients. Hence, there is strong need to organize more educational and training programs on suicide prevention so that these budding health professionals could be more equipped and trained to manage these suicidal patients. PMID:25013311

  11. Nursing students' attitude toward suicide prevention.

    Science.gov (United States)

    Nebhinani, Naresh; Mamta; Gaikwad, Achla D; Tamphasana, L

    2013-07-01

    Preventing suicide depends upon different health professionals' knowledge regarding suicide, attitude toward suicide attempters, skills to assess and manage suicidal risk. This study was aimed to assess the attitude of nursing students toward suicide prevention. 308 nursing students were recruited from the two institutions through total enumeration method. Attitude toward suicide prevention scale was administered. Study design was cross-sectional. Majority were single females, from urban locality, who were pursuing BSc Nursing with the mean age of 20 years. Only minority had previous exposure to suicide prevention programs or workshops. Nearly half of the subjects had positive attitude toward working with suicidal patients. Again half of the subjects considered unemployment and poverty as main causes of suicide and were quite hopeless about it and they also perceived that most of the suicidal people would not reveal their suicidal plans to others. Merely half of the students had positive attitude toward working with suicidal patients. Hence, there is strong need to organize more educational and training programs on suicide prevention so that these budding health professionals could be more equipped and trained to manage these suicidal patients.

  12. Suicide acceptability as a mechanism of suicide clustering in a nationally representative sample of adolescents.

    Science.gov (United States)

    Kleiman, Evan M

    2015-05-01

    The goal of the present study was to examine suicide acceptability as a mechanism of suicide clustering in adolescents. Data were drawn from The National Annenberg Survey of Youth, a sample of 3302 adolescents aged 14-22 collected between 2002 and 2004. Results indicated that beliefs of the acceptability of suicide partially mediated the effect of exposure to suicide (defined as knowing someone who attempted or completed suicide) on 1) serious suicidal ideation and 2) suicide planning behaviors. The present study demonstrated that suicide acceptability is in small part a possible reason why suicides tend to cluster in adolescents. It contributes not only to the knowledge of how the phenomenon of suicide clustering might occur, but more broadly highlights the importance of examining mediators of suicide clustering. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Why not Commercial Assistance for Suicide? On the Question of Argumentative Coherence of Endorsing Assisted Suicide.

    Science.gov (United States)

    Kipke, Roland

    2015-09-01

    Most people who endorse physician-assisted suicide are against commercially assisted suicide - a suicide assisted by professional non-medical providers against payment. The article questions if this position - endorsement of physician-assisted suicide on the one hand and rejection of commercially assisted suicide on the other hand - is a coherent ethical position. To this end the article first discusses some obvious advantages of commercially assisted suicide and then scrutinizes six types of argument about whether they can justify the rejection of commercially assisted suicide while simultaneously endorsing physician-assisted suicide. The conclusion is that they cannot provide this justification and that the mentioned position is not coherent. People who endorse physician-assisted suicide have to endorse commercially assisted suicide as well, or they have to revise their endorsement of physician-assisted suicide. © 2014 John Wiley & Sons Ltd.

  14. HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters.

    Science.gov (United States)

    Jokinen, Jussi; Samuelsson, Mats; Nordström, Anna-Lena; Nordström, Peter

    2008-11-01

    A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in depressed women has been associated with violent suicide attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels are related to suicidal behaviour. We studied the HPT axis function in twelve male suicide attempters and eight healthy volunteers submitted to lumbar puncture and to TRH test. Suicidal behaviour and depression severity were assessed. There was no association between deltamaxTSH and violent suicidality or subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide attempters. The plasma T3 showed a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic regulatory mechanisms on the thyroid hormone activity may be altered in male suicide attempters.

  15. Coming out to talk about suicide: gay men and suicidality.

    Science.gov (United States)

    McAndrew, Sue; Warne, Tony

    2010-04-01

    International studies report increased rates of mental health problems and subsequent suicidality among homosexual populations. While international health-care policy is concerned with reducing suicide among young people, important research findings relating to gay people and suicidality remain unacknowledged in the Suicide Prevention Strategy for England. This qualitative study, utilizing single case studies, was used to gain an in-depth understanding of the life experiences contributing to the suicidality of four gay men. The methodology was psychoanalytically informed, using free association narrative interviewing. The initial data analysis involved interpretation of each of the case studies and a subsequent analysis exploring the shared experiences found in each of the individual narratives. Thematically, these are described as 'knowing and not knowing', 'the centrality of the father-son relationship', 'the loneliness of outsiderness', 'leading a double life', and 'crime and punishment'. The significance of the life experiences these themes illustrate reveal why some gay men might not only experience long-term mental health problems, but also engage in suicidality. Individually and collectively, the analyses provide important insights for mental health nurses becoming more attuned to provide sensitive mental health care to those who have a gay sexual orientation.

  16. Suicide method runs in families: a birth certificate cohort study of adolescent suicide in Taiwan.

    Science.gov (United States)

    Lu, Tsung-Hsueh; Chang, Wan-Ting; Lin, Jin-Jia; Li, Chung-Yi

    2011-12-01

    Suicide method used by adolescents was examined to determine if it was the same as that employed by their suicidal parents. Six hundred eighty adolescents completed suicide between 1997 and 2007, of whom 12 had parents who had previously died by suicide. The suicide method used by these adolescents was compared with that employed by their suicidal parent and that of a matched peer control adolescent with no exposure to parental suicide and living in the same area. In 10 of the 12 suicidal parent-adolescent dyads, the same suicide method was employed by parent and adolescent. Of seven adolescents whose age at parental suicide was 15 years or above, six used the same suicide method as their suicidal parent had. On the contrary, of 12 exposure-nonexposure suicidal adolescent dyads, the same method was used in only four. Adolescents exposed to parental suicide are more likely to use the suicide method employed by their suicidal parents than the method used by adolescent peers with no exposure to parental suicide. © 2011 The American Association of Suicidology.

  17. Mysore study: A study of suicide notes.

    Science.gov (United States)

    Namratha, P; Kishor, M; Sathyanarayana Rao, T S; Raman, Rajesh

    2015-01-01

    Suicide is one of the leading causes of preventable deaths. Recent data suggest South India as one of the regions with highest suicide rates in the world. In 2013, 134,799 people committed suicide in India according to the statistics released by the National Crime Records Bureau. Suicide note is one of the most important sources to understand suicide, which may be beneficial in suicide prevention. Studies on suicidal notes from this part of the world are sparse. The aim was to study the themes in suicide notes that might be useful in prevention strategies. A descriptive study of all suicide notes of those individuals who committed suicide between 2010 and 2013 available with Police Department, Mysore district was obtained and analyzed. A total of 22 suicide note were available. A majority of suicide note was in age group of 16-40 years (86%) and most were men (59%). All suicide notes were handwritten, the majority (70%) in regional language Kannada. Length of notes varied from just few words to few pages. Contents of suicide notes included apology/shame/guilt (80%), love for those left behind (55%) and instruction regarding practical affairs (23%). Most have blamed none for the act (50%). 23% mentioned that they are committing suicide to prove their innocence. 32% mentioned a last wish. The majority of suicidal note contained "guilt" which is a strong indicator of possible depression in deceased. Creating awareness about suicide among public and ensuring access to professionals trained in suicide prevention is need of the hour in this part of the world.

  18. Environmental stimuli modulate the circadian rhythm of [3H-methyl]thymidine incorporation into brain DNA of male rats.

    Science.gov (United States)

    Zucconi, G G; Crognale, M C; Bassetti, M A; Giuditta, A

    1990-12-14

    A circadian rhythm of DNA synthesis is present in most organs of adult mammals, with peak levels (acrophase) generally in the rest period. We have recently reported that in the rat brain the acrophase of the rhythm of thymidine incorporation into DNA occurs on the contrary during the active period. To determine whether the brain waking activity was exerting a modulatory action we measured the circadian rhythm of incorporation in the brain and kidney of young adult male rats housed in conditions of sensory and social enrichment or impoverishment for four days. Biochemical and autoradiographic data show that the brain rhythm persists in the enriched condition, but is abolished in the impoverished condition. On the other hand, the rhythm of incorporation in the kidney is maintained in both conditions. These results suggest that the permanence of the brain oscillation is selectively dependent on the complexity of the sensory and social stimulation.

  19. Prognostic significance of numeric aberrations of genes for thymidylate synthase, thymidine phosphorylase and dihydrofolate reductase in colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Søren Astrup; Vainer, B.; Witton, C.J.

    2008-01-01

    ) in colorectal cancer, and to evaluate its prognostic significance following adjuvant chemotherapy, since these enzymes are closely related to efficacy of 5-fluorouracil (5FU). PATIENTS AND METHODS: Consecutive patients (n = 314), who were completely resected for colorectal cancer stages II-IV and adjuvantly......BACKGROUND: Most human cancer cells have structural aberrations of chromosomal regions leading to loss or gain of gene specific alleles. This study aimed to assess the range of gene copies per nucleus of thymidylate synthase (TYMS), thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR...... the median were compared. Also TYMS expression, assessed by immunohistochemistry, was associated with TYMS copies per nucleus. RESULTS: The number of gene copies per nucleus were 1.7 (0.7-2.8), 1.8 (0.9-3.1) and 1.8 (1.1-2.7) median (range) for TYMS, TP and DHFR, respectively. TYMS expression was directly...

  20. Radiotoxicity and incorporation of methyl-tritiated-thymidine on preimplantation mouse embryo. In vitro fertilization and culture

    International Nuclear Information System (INIS)

    Kikuchi, O.K.; Ohyama, H.; Yamada, T.

    1993-04-01

    In the present work different concentrations of methyl- 3 H-thymidine was added to the culture medium micro drops containing the mouse zygotes at pro nuclear stage and the embryos were cultured in vitro at 37 0 C in a humidified atmosphere with 5% of CO 2 for four days up to the expanded blastocyst stage, the established end point to calculate the L D 50 lethal dose. The blastocyst formation rate decreased with increasing concentration of tritium in medium and a value of 2.4 X 10 3 Bq/ml for L D 50 was obtained. The 3 H-Td R incorporation by the embryo during the preimplantation period was low at the beginning and increased quickly during the morula and the blastocyst development. (author)

  1. Activity of an attached and free-living Vibrio sp. as measured by thymidine incorporation, rho-iodonitrotetrazolium reduction, and ATP/DNA ratios

    International Nuclear Information System (INIS)

    Jeffrey, W.H.; Paul, J.H.

    1986-01-01

    Three independent techniques, [ 3 H]thymidine incorporation, the reduction rate of p-iodonitrotetrazolium violet (INT) to INT formazan normalized to DNA, and the ratio of ATP to DNA, were adapted to measure the activity of attached and unattached estuarine bacteria. In experiments employing the estuarine isolate Vibrio proteolytica, nutrient concentrations were manipulated by varying the concentration of peptone-yeast extract. In the presence of exogenous nutrients, the activity of free-living cells was greater than that of attached cells as measured by [ 3 H]thymidine incorporation and ATP/DNA ratios. In the absence of peptone-yeast extract, however, the activity of attached cells surpassed that of free-living cells as determined by [ 3 H]thymidine incorporation and INT formazan normalized to DNA. Of the three techniques, [ 3 H]thymidine incorporation was deemed most sensitive for detecting changes in activity resulting from slight differences in nutrient concentration. By this technique, attached cells were much less sensitive to changing nutrient concentrations than were free-living cells. Below a threshold concentration, attached cell activity remained constant, while the activity of unattached cells decreased as a function of decreasing nutrient concentration. The results suggest that loss of cell surface area available for substrate uptake due to attachment may be an important factor in determining the relative activities of attached and free-living cells

  2. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue based regimens in ART-naïve and experienced patients

    DEFF Research Database (Denmark)

    Silberstein, F; Cozzi-Lepri, A; Ruiz, L

    2007-01-01

    BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started ...

  3. Experimental investigation of the late effects of ionizing radiation on the cornea, 2. /sup 3/H-thymidine autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Oinaka, M. (Hiroshima Univ. (Japan). School of Medicine)

    1981-06-01

    /sup 3/H-thymidine-labeled cells of the corneal epithelium in the rabbits were examined at various time intervals after /sup 60/Co gamma-ray irradiation (3,000 - 1,500 rad, single exposure, dose rate 40 rad/min.). Then, the relation between /sup 3/H-labeling rates and histological changes of the corneal epithelium after gamma-irradiation was investigated. In the 1,500 rad-exposed series, the /sup 3/H-labeling rates of the epithelial cells decreased during the first week after irradiation, but revealed the ''overshooting'' phenomenon at 2 - 3 weeks post-irradiation, subsequently returned to the control level at 5 weeks. Histological changes of the corneal epithelium after 1,500 rad irradiation were not serious: For instance, loosing of the basal cells was observed. In the 2,500 rad-exposed series, the /sup 3/H-labeling rates of the epithelial cells decreased at 24 hours after irradiation. Subsequently increased slowly during 5 weeks post-irradiation, and reached the control level at 5 weeks. The basal cells of these corneas lost its characteristic ''peg shape'', becoming flat in parallel with the corneal stroma at 5 weeks after irradiation. There was a tendency to restore histological changes. In 3,000 rad-exposed series, the /sup 3/H-labeling rates of the epithelial cells decreased severely at 24 hours after irradiation, never returning to the control level. The coneal epithelium became thin at 5 weeks post-irradiation, resulting in the ulceration. As mentioned above, the histological changes in the corneal epithelium after gamma-ray irradiation reflected the patterns of variation in their /sup 3/H-thymidine labeling rates. It is presumable that the corneal epithelial disorders after irradiation reflect the extent of ''mitosis inhibition'' of these corneal epithelium.

  4. Suicide by self-incineration

    DEFF Research Database (Denmark)

    Leth, Peter Mygind; Hardt-Madsen, Michael

    1997-01-01

    was 43 years, with a broad age range (20-87). Many incidents of self-incineration as a form of political protest were reported in the press especially during the 1960s and 1970s, and the press reports often inspired others to commit suicide in the same way. None of the cases in our investigation were...... victims were of Danish origin, and a religious motive played no significant role. Most of the victims were suffering from mental illness, and a majority had tried to commit suicide before. None of the victims left a suicide note. The scene was most often at home and indoors--only a minority committed...... suicide in remote areas of the countryside. Most were found dead at the scene, and the cause of death was usually heat exposure. Only a minority had a lethal carboxy-hemoglobin (CO-Hb) concentration. It is concluded that close cooperation between police, fire experts, and the forensic pathologist...

  5. The psychology of suicide terrorism.

    Science.gov (United States)

    Post, Jerrold M; Ali, Farhana; Henderson, Schuyler W; Shanfield, Steven; Victoroff, Jeff; Weine, Stevan

    2009-01-01

    This paper reviews current understandings of the psychology of suicide terrorism for psychiatrists and other mental health professionals to help them better understand this terrifying phenomenon. After discussing key concepts and definitions, the paper reviews both group and individual models for explaining the development of suicide terrorists, with an emphasis on "collective identity." Stressing the importance of social psychology, it emphasizes the "normality" and absence of individual psychopathology of the suicide bombers. It will discuss the broad range of terrorisms, but will particularly emphasize terrorism associated with militant Islam. The article emphasizes that comprehending suicide terrorism requires a multidisciplinary approach that includes anthropological, economic, historical, and political factors as well as psychological ones. The paper concludes with a discussion of implications for research, policy, and prevention, reviewing the manner in which social psychiatric knowledge and understandings applied to this phenomenon in an interdisciplinary framework can assist in developing approaches to counter this deadly strategy.

  6. Anti-depressants and suicide.

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E; Norberg, Karen

    2009-05-01

    Suicide takes the lives of around a million people each year, most of whom suffer from depression. In recent years there has been growing controversy about whether one of the best-selling anti-depressants - selective serotonin reuptake inhibitors (SSRIs) - increases or decreases the risk of completed suicide. Randomized clinical trials are not informative in this application because of small samples and other problems. We present what we believe are the most scientifically credible estimates to date on how SSRI sales affect suicide mortality using data from 26 countries for up to 25 years. We exploit just the variation in SSRI sales that can be explained by institutional differences in how drugs are regulated, priced, and distributed, as reflected by the sales growth of new drugs more generally. We find an increase in SSRI sales of 1 pill per capita (12% of 2000 sales levels) reduces suicide by 5%.

  7. Suicides in men with IDDM

    DEFF Research Database (Denmark)

    Kyvik, K O; Stenager, E N; Green, A

    1994-01-01

    OBJECTIVE: To investigate the occurrence of suicide in men with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: A cohort of all Danish men born between 1949 and 1964 (including 1964) who were diagnosed with IDDM before age 20 (n = 1,682) was ascertained earlier. Follow...... ratios (SMRs), adjusted for age and calendar time, were calculated. RESULTS: Among the 168 deaths recorded during follow-up, 15 took place in connection with the onset of IDDM and have been excluded. Of the remaining 153 deaths, 12 were officially classified as suicides (SMR 12/7.48 = 1.6, 0.05 ....1); as for the age-group of 20-24 years, SMR was 2.98, P suicides; as for deaths of unknown causes, three could be reclassified as probable suicides...

  8. Firearm suicide among older men.

    Science.gov (United States)

    Adamek, M E; Kaplan, M S

    1996-03-01

    Data from the Compressed Mortality File for the years 1979 to 1991 were analyzed to determine epidemiologic trends in the rates of suicide by firearms among three age groups of white and black men age 65 and older (65 to 74 years, 75 to 84 years, and 85 years and older). In 1991, among men age 65 and older, firearms accounted for 80 percent of all suicides. Firearm suicide rates increased significantly over time among white men in all three age groups, especially those age 75 and older, and among black men between the ages of 75 and 84. Clinicians should regularly conduct a firearm-availability history with elderly men who are depressed or suicidal.

  9. Suicide and Chronic Traumatic Encephalopathy.

    Science.gov (United States)

    Iverson, Grant L

    2016-01-01

    For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.

  10. Suicide Prevention Strategies for Improving Population Health.

    Science.gov (United States)

    Wilcox, Holly C; Wyman, Peter A

    2016-04-01

    Suicide is a public health problem that accounts for more than 1 million deaths annually worldwide. This article addresses evidence-based and promising youth suicide prevention approaches at the primary, secondary, and tertiary levels. Coordinated, developmentally timed, evidence-based suicide prevention approaches at all intervention levels are likely to reduce youth suicide. For most youth who die by suicide, there are opportunities for intervention before imminent risk develops. Current research in suicide prevention points to the value of investing in "upstream" universal interventions that build skills and resilience as well as policies that enable access to care and protection from lethal means. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Suicide with Shotgun: A Case Report

    Directory of Open Access Journals (Sweden)

    Ali Yildirim

    2011-03-01

    Full Text Available Suicide appears to be a major public health problem in our country and all over the World. Suicide methods will vary between the various communities the most common types of suicides are hanging, using chemicals and using firearms (pistol, shotgun. Connected with easy availability of shotguns suicide cases with using shotgun is significantly increasing in recent years. In our study, suicide with a shotgun, are evaluated in terms of shooting range and its features, originate, area of suicide, crime scene, sex and age. [J Contemp Med 2011; 1(1.000: 29-34

  12. Suicide and ethnicity in Malaysia.

    Science.gov (United States)

    Murty, Om Prakash; Cheh, Lo Boon; Bakit, Pangie Anak; Hui, Foo Jhi; Ibrahim, Zarina Binti; Jusoh, Nazirah Binti

    2008-03-01

    This article highlights methods of ending life in different ethnic groups. This inference is drawn from analysis of data from suicidal cases from the University Malaya Medical Centre mortuary. This study also looked at sex, age, social, and employment factors. Kuala Lumpur has sizeable populations of Muslims, Chinese, Indians and Indonesian, etc. This study is based on 251 cases of suicide that were reported at the University Malaya Medical Centre from 2000 to 2004. Malaysia has a population of 22,662,365 people with 3 major ethnic groups: Malay (58%), Chinese (24%), and Indians (8%) with a minority of "others" (10%), which includes foreigners, Sabahan, and Sarawakian. This research found suicides of 164 male (65%) and 87 female (35%) victims. Their age ranged from 15 to 80 years. The age group from 21 to 30 had the highest total cases of suicide (83 of 251; 33.1%). Among ethnic groups highest rate of suicide was among Chinese with a total of 120 cases (120 of 251; 47.8%). As far as lone method of suicide is concerned, hangings accounted for the highest proportion of cases (108 of 251; 43%). Among ethnic groups, jumping from height was the commonest method used by Chinese (49 of 120; 41%), Malay (9 of 16; 56%), and others (15 of 28; 53.4%); whereas, hanging was the commonest method of committing suicide by Indians (49 of 87); Muslims showed the lowest cases of suicide (18 of 251; 7.2%). In poisoning group Indian was the highest ethnic group who used this method (20 of 37; 54.1%).

  13. Alteration of radiation response in vitro by simultaneous modulation of the de novo and salvage pathways to deoxynucleoside triphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine and thymidine analogs

    International Nuclear Information System (INIS)

    Coucke, Philippe A.; Li Yexiong; Cottin, Eliane; Ozsahin, Mahmut; Paschoud, Nicolas; Mirimanoff, Rene-Oliver

    1997-01-01

    Aim: To test different thymidine analogs (zidovudine = AZT, stavudine D4T, and 5-iodo-2-deoxyuridine = IdUrd), active at the level of the salvage pathway, as modifiers of the radiosensitization observed with (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC), an inhibitor of ribonucleotide reductase (RR), a key enzyme in the de novo pathway of deoxynucleoside triphosphate synthesis. The thymidine anologs are interacting with thymidine kinase (TK), the rate-limiting enzyme of the salvage pathway. Materials and methods: A human colon cancer cell line Widr has been exposed for 48 h prior to irradiation to 30 nM of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). Stavudine (D4T) and zidovudine (AZT) were added at a concentration of 25 μM after subcultivation at low density and immediately before irradiation. Iododeoxyuridine (IdUrd) at a concentration of 1 and 2 μM was tested either 48 h before irradiation or applied in the same experimental conditions as D4T or AZT. All the concentrations used were in the physiological range. Prolonged exposure to IdUrd prior to irradiation was tested because of its known radiosensitizing effect. The experimental endpoint was clonogenic survival as measured by a colony forming assay. Results: The different drugs used alone or in combination did not modify significantly the PE of unirradiated WiDr-cells. As previously shown 30 nM FMdC for 48 h, resulted in a small but significant change in the radiation response. The enhancement ratio (SF%-control divided by SF%-drug) at a 2 Gy dose level was 1.20 ± 0.03 for cells exposed to FMdC. AZT and D4T added after subcultivation before irradiation yielded an ER of 1.12 ± 0.05 and 1.13 ± 0.09 respectively. The combination of FMdC and D4T resulted in an ER of 1.39 ± 0.04, whereas AZT combined to FMdC yielded 1.64 ± 0.21. For IdUrd alone, an ER was reached of 1.17 ± 0.05, 1.22 ± 0.08 at 1 and 2 μM respectively if applied immediately after subcultivation, and 1.17 ± 0.06 at 1 μM applied for 48

  14. National Suicide Registry Malaysia (NSRM).

    Science.gov (United States)

    Hayati, A N; Kamarul, A K

    2008-09-01

    To create a nationwide system to capture data on completed suicide in Malaysia i.e. the morbidity, geographic and temporal trends and the population at high risk of suicide. Data from this registry can later be used to stimulate and facilitate further research on suicide. This paper describes the rationale and processes involved in developing a national suicide registry in 2007. The diagnosis of suicide is based on the ICD-10 codes for fatal intentional self-harm (X60-X84). A case report form with an accompanying instruction manual had been prepared to ensure systematic and uniform data collection. State Forensic Pathologist's offices are responsible for data collection in their respective states, and in turn will submit the data to a central data management unit. Data collection began in July 2007 and currently in data cleaning process. Training for source data producers is ongoing. In 2008, the NSRM plans to involve university hospitals into its network as currently only Ministry of Health hospitals are involved. The NSRM will be launching its online application for case registration this year while an overview of results will be available via its public domain at www.nsrm.gov.my beginning 20 April 2008. To efficiently capture the data on suicide, a concerted effort between various agencies is needed. A lot of conceptual work and data base development remains to be done in order to position preventive efforts on a more solid foundation.

  15. [Active euthanasia, or assisted suicide?

    Science.gov (United States)

    Julesz, Máté

    2016-10-01

    Both active euthanasia and assisted suicide are legal in The Netherlands, Belgium, Luxemburg and, most recently, in Canada. Examination of national legislations of countries where both active euthanasia and assisted suicide are legal. The number of accomplished active euthanasia cases and that of assisted suicide cases. Analysis of national statistical data. Comparison of statistical data before and after 2010. Comparison of the related practices in the surveyed countries. The number of active euthanasia cases markedly predominates over the number of assisted suicide cases. Cancer is a main reason for active euthanasia, or assisted suicide. In countries with a larger population, the number of active euthanasia cases is higher than that in countries with a smaller population. Regarding the fact that the applicants for active euthanasia withdraw their requests in a smaller number than the applicants for assisted suicide, patients prefer the choice of active euthanasia. Since the related legislative product is too recent in Canada at present, it may be only presumed that a certain preference will also develop in the related practices in Canada. Orv. Hetil., 2016, 157(40), 1595-1600.

  16. Psychotic Depression and Suicidal Behavior.

    Science.gov (United States)

    Fredriksen, Kristin J; Schoeyen, Helle K; Johannessen, Jan O; Walby, Fredrik A; Davidson, Larry; Schaufel, Margrethe A

    2017-01-01

    This study investigated how severely depressed individuals experienced the relationship between psychotic symptoms and suicidal ideation and behavior. Semi-structured qualitative interviews were conducted with a purposive sample of nine inpatients from a psychiatric university hospital between September 2012 and May 2013 fulfilling diagnostic criteria for a psychotic depressive episode as part of a unipolar or bipolar disorder. Analysis was conducted using systematic text condensation. Participants experienced (1) being directed to perform impulsive potentially fatal actions, (2) feeling hounded to death, (3) becoming trapped in an inescapable darkness, and (4) being left bereft of mental control. They described how impulsivity directed by delusions and hallucinations resulted in unpredictable actions with only moments from decision to conduct. Suicide was seen as an escape not only from life problems but also from psychotic experiences and intense anxiety. Participants reported being in a chaotic state, unable to think rationally or anticipate the consequences of their actions. Their ability to identify and communicate psychotic symptoms and suicidal ideation and behavior was compromised, leaving them to struggle alone with these terrifying experiences. Suicide risk assessments based on verbal reports from individuals with psychotic depression may not always be valid due to potential impulsivity and underreporting of suicidal ideation. It may be important for clinicians to explore the delusional content of such patients' experiences to assess the possibility of suicide as a result of shame, guilt, remorse, or altruistic intentions to save others from harm.

  17. Stimulated mitogen-activated protein kinase is necessary but not sufficient for the mitogenic response to angiotensin II. A role for phospholipase D.

    Science.gov (United States)

    Wilkie, N; Morton, C; Ng, L L; Boarder, M R

    1996-12-13

    Activation of the mitogen-activated protein kinase (MAPK) cascade has been widely associated with cell proliferation; previous studies have shown that angiotensin II (AII), acting on 7-transmembrane G protein-coupled receptors, stimulates the MAPK pathway. In this report we investigate whether the MAPK pathway is required for the mitogenic response to AII stimulation of vascular smooth muscle cells derived from the hypertensive rat (SHR-VSM). AII stimulates the phosphorylation of MAPK, as determined by Western blot specific for the tyrosine 204 phosphorylated form of the protein. This MAPK phosphorylation was inhibited by the presence of the inhibitor of MAPK kinase activation, PD 098059. Using a peptide kinase assay shown to measure the p42 and p44 isoforms of MAPK, the stimulated response to AII was inhibited by PD 098059 with an IC50 of 15.6 +/- 1.6 microM. The AII stimulation of [3H]thymidine incorporation was inhibited by PD 098059 with an IC50 of 17.8 +/- 3.1 microM. PD 098059 had no effect on AII-stimulated phospholipase C or phospholipase D (PLD) activity. When the SHR-VSM cells were stimulated with phorbol ester, there was an activation of MAPK similar in size and duration to the response to AII, but there was no significant enhancement of [3H]thymidine incorporation. There was also no activation of PLD by phorbol ester, while AII produced a robust PLD response. Diversion of the product of the PLD reaction by 1-butanol caused a partial loss of the [3H]thymidine response; this did not occur with tertiary butanol, which did not interfere with the PLD reaction. These results show that in these cells the MAPK cascade is required but not sufficient for the mitogenic response to AII, and suggest that the full mitogenic response requires both MAPK in conjunction with other signaling components, one of which is PLD.

  18. Formation of cyclic 1,N2-propanodeoxyguanosine and thymidine adducts in the reaction of the mutagen 2-bromoacrolein with calf thymus DNA

    International Nuclear Information System (INIS)

    Meerman, J.H.; Smith, T.R.; Pearson, P.G.; Meier, G.P.; Nelson, S.D.

    1989-01-01

    The interaction of the mutagen 2-bromoacrolein (2BA) with DNA and thymidine was studied in vitro by reaction of [3-3H]2BA with thymidine, RNA, single-stranded DNA, and double-stranded DNA in phosphate buffer (pH 7.4). After purification of the nucleic acids, they were incubated at alkaline pH to convert any (hydroxybromo)propano(deoxy)-guanosine adducts to their dihydroxy analogues. After acid or enzymatic hydrolysis, the hydrolysates were analyzed by reversed-phase high-performance liquid chromatography. At a concentration of 1.6 mM, the fraction of 2BA that became covalently bound to DNA was 2.3% of the amount added. Only 3% of the radioactivity bound to DNA after extensive purification could be accounted for as cyclic 1,N2-(6,7-dihydroxy)-propanoguanine adducts. More 2BA became covalently bound to single-stranded DNA and RNA as compared with double-stranded DNA. However, high-performance liquid chromatographic analyses showed that formation of cyclic 1,N2-(6,7-dihydroxy)propanoguanine adducts was also a minor reaction with these macromolecules. Because these data showed that other type(s) of reaction(s) are more important in the reaction of 2BA with nucleic acids, we have investigated the reaction of 2BA with other nucleosides. It was found that 2BA reacted well with thymidine in vitro, and the major product was identified by 500 MHz 1H and 75.43 MHz 13C nuclear magnetic resonance and thermospray mass spectrometry as 3-(2-bromo-3-oxopropyl)thymidine. This adduct was unstable and decomposed upon storage. After enzymatic hydrolysis of [3H]2BA-modified double-stranded DNA and subsequent analysis of the hydrolysate by high-performance liquid chromatography, 22% of the covalently bound radioactivity to DNA coeluted with decomposition products of the 3-(bromooxypropyl)thymidine adduct

  19. Neurogenesis in the vomeronasal epithelium of adult garter snakes: 3. Use of 3H-thymidine autoradiography to trace the genesis and migration of bipolar neurons

    International Nuclear Information System (INIS)

    Wang, R.T.; Halpern, M.

    1988-01-01

    Use of 3H-thymidine autoradiography and unilateral vomeronasal (VN) axotomy has permitted us to demonstrate directly the existence of VN stem cells in the adult garter snake and to trace continuous bipolar neuron development and migration in the normal VN and deafferentated VN epithelium in the same animal. The vomeronasal epithelium and olfactory epithelium of adult garter snakes are both capable of incorporating 3H-thymidine. In the sensory epithelium of the vomeronasal organ, 3H-thymidine-labeled cells were initially restricted to the base of the undifferentiated cell layer in animals surviving 1 day following 3H-thymidine injection. With increasing survival time, labeled cells progressively migrated vertically within the receptor cell column toward the apex of the bipolar neuron layer. In both the normal and denervated VN epithelium, labeled cells were observed through the 56 days of postoperative survival. In the normal epithelium, labeled cells were always located within the matrix of the intact receptor cell columns. However, labeled cells of the denervated epithelium were always located at the apical front of the newly formed cell mass following depletion of the original neuronal cell population. In addition, at postoperative days 28 and 56, labeled cells of the denervated VN epithelium achieved neuronal differentiation and maturation by migrating much farther away from the base of the receptor cell column than the labeled cells on the normal, unoperated contralateral side. This study directly demonstrates that basal cells initially incorporating 3H-thymidine are indeed stem cells of the VN epithelium in adult garter snakes

  20. Predictors of Suicide Attempts in Clinically Depressed Korean Adolescents

    Science.gov (United States)

    Kwon, Ahye; Song, Jungeun; Yook, Ki-Hwan; Jon, Duk-In; Jung, Myung Hun; Hong, Narei; Hong, Hyun Ju

    2016-01-01

    We examined predictors of suicide attempts in clinically depressed adolescents in Korea and gender differences in suicidal behavior. In total, 106 adolescents diagnosed with depressive disorder were recruited in South Korea. We assessed various variables that might affect suicide attempts, and used a structured interview for the diagnosis of depression and comorbidities and to evaluate suicidality. Demographic and clinical characteristics of the subjects were compared between suicide attempt and non-suicide attempt groups and we examined significant predictors of suicide attempts. Gender differences in suicidal ideation and suicidal behavior were also analyzed. Among 106 depressed participants, 50 (47.2%) adolescents were classified in the suicide attempt group. Generally, the suicide attempt and non-suicide attempt group shared similar clinical characteristics. The suicide attempt group had more females, more major depressive disorder diagnoses, more depressive episodes, and higher suicidal ideation than the non-suicide attempt group. Suicidal ideation was the only significant predictor of suicidal attempt, regardless of gender. Higher suicidal ideation frequency scores and more non-suicidal self-injurious behaviors were shown in the female suicide attempt group than the male suicide attempt group. It is recommended that suicidal ideation be assessed regularly and managed rigorously to decrease suicide risks in depressive adolescents. PMID:27776392

  1. Antidepressants and Suicide Risk: A Comprehensive Overview

    Directory of Open Access Journals (Sweden)

    Roberto Tatarelli

    2010-08-01

    Full Text Available The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year, with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.

  2. Predicting Suicidal Ideation with the Depression Hopelessness and Suicide Screening Form (DHS)

    Science.gov (United States)

    Mills, Jeremy F.; Kroner, Daryl G.

    2008-01-01

    The current study examines a series of interactions between a prior history of suicidal behavior and cognitions permissive of suicide, and the variables of depression and hopelessness in the relationship with suicidal ideation in two samples of incarcerated offenders. Results indicate that both a prior history of suicidal behavior and cognitions…

  3. Suicides and Suicide Attempts in the U.S. Military, 2008-2010

    Science.gov (United States)

    Bush, Nigel E.; Reger, Mark A.; Luxton, David D.; Skopp, Nancy A.; Kinn, Julie; Smolenski, Derek; Gahm, Gregory A.

    2013-01-01

    The Department of Defense Suicide Event Report Program collects extensive information on suicides and suicide attempts from the U.S. Air Force, Army, Marine Corps, and Navy. Data are compiled on demographics, suicide event details, behavioral health treatment history, military history, and information about other potential risk factors such as…

  4. A Comparison of Suicide Note Writers with Suicides Who Did Not Leave Notes

    Science.gov (United States)

    Callanan, Valerie J.; Davis, Mark S.

    2009-01-01

    There is disagreement in the suicide literature on the value of suicide notes as a data source, particularly regarding the extent to which suicide decedents who write notes differ from those who do not. Using 10 years of suicide cases from Summit County, Ohio, these two groups were compared on 40 variables including sociodemographic…

  5. Gratitude and Suicidal Ideation and Suicide Attempts among Chinese Adolescents: Direct, Mediated, and Moderated Effects

    Science.gov (United States)

    Li, Dongping; Zhang, Wei; Li, Xian; Li, Nini; Ye, Baojuan

    2012-01-01

    In a sample of 1252 Chinese adolescents (mean age = 15.00 years), this study examined the direct relations between gratitude and adolescents' suicidal ideation and suicide attempts. This study also examined indirect relations between gratitude and suicidal ideation and suicide attempts via two self-system beliefs--coping efficacy and self-esteem.…

  6. An Application of Durkheim's Theory of Suicide to Prison Suicide Rates in the United States

    Science.gov (United States)

    Tartaro, Christine; Lester, David

    2005-01-01

    E. Durkheim (1897) suggested that the societal rate of suicide might be explained by societal factors, such as marriage, divorce, and birth rates. The current study examined male prison suicide rates and suicide rates for men in the total population in the United States and found that variables based on Durkheim's theory of suicide explained…

  7. Tolerance of suicide, religion and suicide rates : an ecological and individual study in 19 Western countries

    NARCIS (Netherlands)

    Neeleman, J; Halpern, D; Leon, D; Lewis, G

    Background. Negative associations between religion and suicide, in individuals and countries, may be mediated by the degree to which suicide is tolerated. Methods. Linear regression was used to examine ecological associations between suicide tolerance, religion and suicide rates in 19 Western

  8. Turkish Imams' Experience with and Their Attitudes Toward Suicide and Suicidal Persons.

    Science.gov (United States)

    Eskin, Mehmet

    2017-06-01

    This study investigated the experience with and attitudes toward suicide and suicidality in 70 consenting imams serving in mosques in the province of Aydin which is located at the southwest part of Turkey. A self-report questionnaire was used to collect the data. Attitudes of imams to suicide and suicidality were compared with attitudes of male university students. Only 4 imams (5.7 %) reported having had suicidal thoughts in past, and none reported having attempted suicide. Almost 50 % said that someone in communities they serve has commited suicide and nearly 40 % reported leading funeral ceremony for someone who committed suicide. Majority of imams (64.3 %) were of the opinion that a funeral ceremony should be arranged for people who suicide and 87.1 % were of the opinion that people who suicide can be buried in a common cemetery, but only 21.4 % said that someone who attempted suicide can be appointed as imam. Compared to male medical students, imams saw suicide as an unacceptable option and those engaging in suicidal behavior to be punished after death. But they displayed socially accepting and helping reactions to an imagined close friend who attempted suicide. Therefore, it was concluded that imams might exhibit preventive reactions to suicide when they offer counseling for persons from their congregations during times of suicidal crises.

  9. The Press Coverage of Celebrity Suicide and the Development of Suicide Frequencies in Germany.

    Science.gov (United States)

    Schäfer, Markus; Quiring, Oliver

    2015-01-01

    The existence of the so-called "Werther effect" is well confirmed, and there are several recommendations on how the media should (not) report suicide to minimize the risk of copycat behavior. Unfortunately, very little is known about how suicide is actually reported. The article examines the German press coverage of six celebrity suicides with respect to compliance with guidelines on suicide reporting and analyzes changes in suicides in the wake of the reporting. It concludes that German media do not respect the recommendations in a substantial number of their articles. In addition, a significant increase in suicides and similar suicides is found.

  10. Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Wang, August G

    2009-01-01

    BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult...... the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4...

  11. Internet suicide in Japan: a qualitative content analysis of a suicide bulletin board.

    Science.gov (United States)

    Ikunaga, Ai; Nath, Sanjay R; Skinner, Kenneth A

    2013-04-01

    Netto shinju, or Internet group suicide, is a contemporary form of Japanese suicide where strangers connect on the Internet and make plans to commit suicide together. In the past decade, numerous incidents have occurred whereby young Japanese make contact on the Internet, exchange tips on suicide methods, and make plans to meet offline for group/individual suicide. A systematic qualitative content/thematic analysis of online communications posted on a popular Japanese suicide bulletin board yielded a textured, thematic understanding of this phenomenon. Themes identified reflected Shneidman's theory of suicide but with an emphasis on interpersonal concerns that are embedded in Japanese culture.

  12. Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior.

    Science.gov (United States)

    Mallick, Faryal; McCullumsmith, Cheryl B

    2016-06-01

    Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine's action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior.

  13. Suicide to harass others: clues from mythology to understanding suicide bombing attacks.

    Science.gov (United States)

    Preti, Antonio

    2006-01-01

    Suicide by revenge, the Samsonic suicide, and the suicide by devotio, all described in classical mythology and also reported in the ethnographic literature, belong to the same class of suicidal behaviors as kamikaze suicide and the suicide bombing attack: suicide to harass and burden others or suicide with a hostile intent. The lack of a social dimension to share in a positive manner may lead an individual to integrate him/herself in another social structure, e.g., a military organization, which allows the individual to express his/her desires and personal identity only by destroying others and themselves. The dynamics of these forms of suicide are also likely to work in other displays of life-threatening behavior, such as family annihilation, mass murder, and spree killing. A more thorough investigation of the dynamics operating in suicide bombing attacks could, therefore, contribute to preventative strategies against violence at large.

  14. Suicide Prevention: Critical Elements for Managing Suicidal Clients and Counselor Liability Without the Use of a No-Suicide Contract

    Science.gov (United States)

    Lee, Jeane B.; Bartlett, Mary L.

    2005-01-01

    Despite its entrenchment as a standard of practice, no-suicide contracts fail to achieve their purpose as an effective part of treatment or as an effective method of inoculating counselors against potential lawsuits should a client commit suicide. Critical elements for managing suicidal clients and counselor liability without reliance on the…

  15. Preventing Suicide in Prisons, Part I Recommendations fromthe International Association for Suicide Prevention Task Force on Suicide in Prisons

    NARCIS (Netherlands)

    Konrad, N.; Daigle, M.S.; Daniel, A.E.; Dear, G.E.; Frottier, P.; Hayes, L.M.; Kerkhof, A.J.F.M.; Liebling, A.; Sarchiapone, M.

    2007-01-01

    In 2000 the Department of Mental Health of the World Health Organization (WHO) published a guide named Preventing Suicide. A Resource for Prison Officers as part of the WHO worldwide initiative for the prevention of suicide. In 2007 there are new epidemiological data on prison suicide, a more

  16. Is suicide an option?: The impact of disability on suicide acceptability in the context of depression, suicidality, and demographic factors.

    Science.gov (United States)

    Lund, Emily M; Nadorff, Michael R; Samuel Winer, E; Seader, Kathleen

    2016-01-01

    Suicide is a major clinical and public health issue, especially in people with disabilities. However, research on the acceptability of suicide in people with disabilities has not directly compared the relative acceptability of suicidality in people with and without disabilities. An online sample of five hundred American adults read five pairs of vignettes about individuals who were experiencing suicidal ideation following a life stressor. Each pair contained a disability and no-disability condition; a sixth pair of vignettes discussed suicidal ideation in an elderly individual and contained physical and cognitive disability conditions. Participants completed questions regarding the relative acceptability of suicidality for each vignette as well as demographic items and measures of suicidality, depressive symptoms, and attitude towards disability. In all vignette five pairs, suicidality was seen as significantly more acceptable in the disability condition; this was true even when the participants themselves had disabilities or friends or family members with disabilities. Suicidality, depressive symptomology, and more negative attitudes towards disability predicted greater acceptability in both conditions; no factors predicted greater differences between the two conditions. The vignettes in this study focused primarily on individuals in their 20s and most did not compare two disabling conditions. The greater social acceptability of suicidality in people with disabilities may be taken by individuals with disabilities who are suicidal as implicit permission to end their lives. The potential impact of such social influences should be assessed and addressed by clinicians and suicide prevention advocates. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Preventing adolescent suicide: a community takes action.

    Science.gov (United States)

    Pirruccello, Linda M

    2010-05-01

    Suicide is the third leading cause of death for adolescents and young people in the United States. The etiology of suicide in this population has eluded policy makers, researchers, and communities. Although many suicide prevention programs have been developed and implemented, few are evidence-based in their effectiveness in decreasing suicide rates. In one northern California community, adolescent suicide has risen above the state's average. Two nurses led an effort to develop and implement an innovative grassroots community suicide prevention project targeted at eliminating any further teen suicide. The project consisted of a Teen Resource Card, a community resource brochure targeted at teens, and education for the public and school officials to raise awareness about this issue. This article describes this project for other communities to use as a model. Risk and protective factors are described, and a comprehensive background of adolescent suicide is provided.

  18. Nocturnal Sleep Disturbances: Risk Factors for Suicide

    Science.gov (United States)

    ... among the elderly (Bernert, 2007) and, mediated by depression, are associated with suicide ideation among the elderly (Nadorff et al., 2013). ... suicidal behavior in the National Longitudinal Study of Adolescent ... (2013) 5 Nocturnal Sleep Disturbances: Risk Factors for ...

  19. Estimating suicide occurrence statistics using Google Trends

    Directory of Open Access Journals (Sweden)

    Ladislav Kristoufek

    2016-11-01

    Full Text Available Abstract Data on the number of people who have committed suicide tends to be reported with a substantial time lag of around two years. We examine whether online activity measured by Google searches can help us improve estimates of the number of suicide occurrences in England before official figures are released. Specifically, we analyse how data on the number of Google searches for the terms ‘depression’ and ‘suicide’ relate to the number of suicides between 2004 and 2013. We find that estimates drawing on Google data are significantly better than estimates using previous suicide data alone. We show that a greater number of searches for the term ‘depression’ is related to fewer suicides, whereas a greater number of searches for the term ‘suicide’ is related to more suicides. Data on suicide related search behaviour can be used to improve current estimates of the number of suicide occurrences.

  20. Suicide in a spinal cord injured population

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

    1998-01-01

    To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI).......To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI)....

  1. Suicide clusters among young Kenyan men.

    Science.gov (United States)

    Goodman, Michael L; Puffer, Eve S; Keiser, Philip H; Gitari, Stanley

    2017-11-01

    Suicide is a leading cause of global mortality. Suicide clusters have recently been identified among peer networks in high-income countries. This study investigates dynamics of suicide clustering within social networks of young Kenya men ( n = 532; 18-34 years). We found a strong, statistically significant association between reported number of friends who previously attempted suicide and present suicide ideation (odds ratio = 1.9; 95% confidence interval (1.42, 2.54); p self-esteem (23% of total effect). Meaning in life further mediated the association between collective self-esteem and suicide ideation. Survivors of peer suicide should be evaluated for suicide risk.

  2. How Veterans Health Administration Suicide Prevention Coordinators Assess Suicide Risk.

    Science.gov (United States)

    Pease, James L; Forster, Jeri E; Davidson, Collin L; Holliman, Brooke Dorsey; Genco, Emma; Brenner, Lisa A

    2017-03-01

    This cross-sectional study was designed to examine the suicide risk assessment practices of Suicide Prevention Coordinators (SPCs) within the Veterans Health Administration. Specifically, this study sought to (1) identify factors SPCs consider most important in assessing risk and patient priority; (2) measure the level of consistency and agreement between SPCs in assessing suicide risk and prioritizing cases; and (3) measure individual SPC consistency between cases. SPCs (n = 63) responded to online survey questions about imminent and prolonged risk for suicide in response to 30 fictional vignettes. Combinations of 12 acute and chronic suicide risk factors were systematically distributed throughout the 30 vignettes using the Fedorov () procedure. The SPCs were also asked to identify the level of priority for further assessment both disregarding and assuming current caseloads. Data were analysed using clinical judgement analysis. Suicidal plan, β = 1.64; 95% CI (1.45, 1.82), and preparatory behaviour, β = 1.40; 95% CI (1.23, 1.57), were considered the most important acute or imminent risk factors by the SPCs. There was less variability across clinicians in the assessment of risk when alcohol use (p = 0.02) and hopelessness (p = 0.03) were present. When considering acute or imminent risk factors, there was considerable variability between clinicians on a vignette-by-vignette basis, median SD = 0.86 (range = 0.47, 1.13), and within individual clinicians across vignettes, median R 2  = 0.80 (0.49, 0.95). These findings provide insight into how this group of providers think about acute and chronic risk factors contributing to imminent suicide risk in Veterans. Copyright © 2016 John Wiley & Sons, Ltd. Identifies factors that practitioners consider most important in suicide risk assessment Discusses how to distinguish between chronic and acute risk for suicide Identifies factors that lead to more consistent clinical judgments. Copyright

  3. Shame-proneness in attempted suicide patients

    Science.gov (United States)

    2012-01-01

    Background It has been suggested that shame may be an important feature in suicidal behaviors. The disposition to react with shame, “shame-proneness”, has previously not been investigated in groups of attempted suicide patients. We examined shame-proneness in two groups of attempted suicide patients, one group of non-suicidal patients and one group of healthy controls. We hypothesized that the attempted suicide patients would be more shame-prone than non-suicidal patients and healthy controls. Methods The Test of Self-Conscious Affect (TOSCA), which is the most used measure of shame-proneness, was completed by attempted suicide patients (n = 175: 105 women and 3 men with borderline personality disorder [BPD], 45 women and 22 men without BPD), non-suicidal psychiatric patients (n = 162), and healthy controls (n = 161). The participants were convenience samples, with patients from three clinical research projects and healthy controls from a fourth research project. The relationship between shame-proneness and attempted suicide was studied with group comparisons and multiple regressions. Men and women were analyzed separately. Results Women were generally more shame-prone than men of the same participant group. Female suicide attempters with BPD were significantly more shame-prone than both female suicide attempters without BPD and female non-suicidal patients and controls. Male suicide attempters without BPD were significantly less shame-prone than non-suicidal male patients. In multiple regressions, shame-proneness was predicted by level of depression and BPD (but not by attempted suicide) in female patients, and level of depression and non-suicidality in male patients. Conclusions Contrary to our hypothesis and related previous research, there was no general relationship between shame-proneness and attempted suicide. Shame-proneness was differentially related to attempted suicide in different groups of suicide attempters, with significantly high

  4. Attitudes of adolescents toward suicidal behavior: permissiveness of suicidal behavior as a risk factor

    Directory of Open Access Journals (Sweden)

    Urška Arnautovska

    2008-04-01

    Full Text Available Throughout history, the social convictions and norms have influenced the recognition and presence of suicidal behaviour in different ways. However, previous research findings regarding the connection between suicidal behaviour and attitudes towards suicide have not arrived at a clear conclusion. The present research explores adolescents' attitudes toward suicide. The aim was to examine the relation between the permissive attitude toward suicide on one side and certain suicide risk factors and satisfaction in different domains of psychical functioning on the other side. Data was collected on 423high school students in three Slovenian cities, chosen on the basis of different regional suicide rates, with an Attitudes towards Suicide Questionnaire ATTS, Psychological Well-Being Scales PWBS, and questions about suicidal behaviour of adolescents and their surroundings. The results showed that the acceptance of suicide is proportional to the suicide rates of different regions. We concluded that permissive attitudes towards suicide could potentially lead to the increased risk of suicidal behaviour. Furthermore, the acceptance of suicide was, inter alia, significantly positively related to the self-reported probability of committing suicide, the presence of suicidal behaviour of the adolescent and his/her friends or other people he/she knows, while the connection with the subjective life satisfaction was negative. Considering the fact that there has been a trend of growing permissiveness towards suicide in society in the last few decades, the findings raise a question regarding the positive effects of such tolerance on suicide rates and support the justification of restrictive attitudes towards suicide as a protective factor of suicidal behaviour.

  5. [Teenagers' suicides and suicide attempts: finding one's way in epidemiologic data].

    Science.gov (United States)

    de Tournemire, R

    2010-08-01

    This paper engages into a global assessment of statistics and their potential uses, ranging from 19th century accounts of "suicidal acts" by the central services of criminal justice in France, to European comparative data on suicide in the years 2000. The most recent facts and figures about teenagers' suicides in France are taken into account, thanks to the Inserm records on deaths by suicide and to public polls on suicidal attempts. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  6. Suicidal thoughts and emotion competence.

    Science.gov (United States)

    Paradiso, Sergio; Beadle, Janelle N; Raymont, Vanessa; Grafman, Jordan

    2016-10-01

    During deployment and upon returning home, veterans experience emotional challenges that test their social and psychological adaptation and place them at risk for suicidal thinking. Individual variability in skill-based capacity to adaptively perceive, understand, correctly use, and manage emotions (called emotional competence) may play a role in the development of psychological suffering and suicidal thinking. Based on research in healthy and clinical samples, poor emotional competence was predicted to be associated with suicidal thinking among returning veterans. Participants were selected from the W. F. Caveness Vietnam Head Injury Study (VHIS) registry, which in the late 1960s began prospectively assessing 1221 veterans). The study sample was composed of veterans examined between 2003 and 2006 and included 185 participants who at the time of assessment with the Beck Depression Inventory (BDI) did (N= 46) or did not endorse (N= 139) suicidal thinking then or during the previous two weeks and received performance-based measures of emotional competence (Mayer-Salovey-Caruso Emotional Intelligence Test; MSCEIT, Version 2.0) and theory of mind. MSCEIT subtests and theory of mind tasks were condensed via principal component analysis: Component 1 (Emotion Processing) included use, understand, and manage emotions tasks, and Component 2 (Emotion Perception) included perceive emotions. Veterans endorsing suicidal thoughts showed poorer emotion processing whereas emotion perception and theory of mind tasks did not show significant group effects. In addition, veterans who endorsed thoughts of suicide were deployed at a younger age, had lower education, and tended to report more negative experiences in social interactions upon return to the United States. The capacity to understand, use, and manage emotionally charged stimuli and situations may represent risk factors for suicidal thinking among veterans.

  7. STUDY OF SUICIDE ATTEMPTS IN SCHIZOPHRENIA

    OpenAIRE

    Jagadeesan Madras Sundararajan; Saravana Jothi Ramalingam; Gajalakshmi Thulasibai Panneerselvam

    2016-01-01

    BACKGROUND Schizophrenia is a major mental illness whose sufferers have been found to have lesser longevity than general population. The most common cause for premature death in schizophrenia is suicide. There are very few Indian studies on suicide in persons suffering from schizophrenia. OBJECTIVES The objectives were to study the frequency of suicide attempt in schizophrenia to compare and study the clinical and sociodemographic profile of suicide attempters and non-attempt...

  8. Suicide Protective Factors Among Trans Adults

    OpenAIRE

    Moody, Ch?rie; Smith, Nathan Grant

    2013-01-01

    A recent study indicated a suicide attempt rate of 41?% among trans (e.g., trans, transgender, transexual/transsexual, genderqueer, two-spirit) individuals. Although this rate is alarming, there is a dearth of literature regarding suicide prevention for trans individuals. A vital step in developing suicide prevention models is the identification of protective factors. It was hypothesized that social support from friends, social support from family, optimism, reasons for living, and suicide re...

  9. Suicide in the Early Stage of Schizophrenia

    OpenAIRE

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects w...

  10. Protective factors against suicidal behavior in Latinos.

    Science.gov (United States)

    Oquendo, Maria A; Dragatsi, Dianna; Harkavy-Friedman, Jill; Dervic, Kanita; Currier, Dianne; Burke, Ainsley Keller; Grunebaum, Michael F; Mann, J John

    2005-07-01

    Latinos appear to be relatively protected against suicidal behavior, but the factors that mediate this effect are not known. Some protective factors may be related to cultural constructs that provide a buffer against suicidal behavior in the face of psychiatric illness. We sought to determine whether the Reasons for Living Inventory (RFLI) might capture protective factors against suicidal behavior in Latinos and non-Latinos. Patients with major depression, bipolar disorder, or schizophrenia were interviewed regarding their depressive symptomatology and lifetime history of suicidal behavior. The RFLI, which measures protective factors against suicidal acts, was also administered. Multivariate analyses were used to assess the relationship between suicide measures, ethnicity, and selected clinical and demographic variables. Although Latinos and non-Latinos did not differ significantly in attempter status (attempter/nonattempter), number of attempts, or suicide intent, Latinos reported significantly less suicidal ideation and made less lethal attempts. On the RFLI, Latinos scored significantly higher on subscales regarding survival and coping beliefs, responsibility to family, and moral objections to suicide, possibly reflective of cultural norms endorsed by Latino groups. Multivariate analyses suggested that although being Latino was independently associated with less suicidal ideation, other suicidal behaviors held a stronger relationship to moral objections to suicide and survival and coping skills than to ethnicity. Self-identification as Latino may be associated with espousing cultural constructs that mediate protective effects against suicidal behavior. Constructs identified in the RFLI may protect Latinos from acting on suicidal thoughts, affecting moral objections to suicide and survival and coping beliefs. Further studies to elucidate the impact of these factors on suicidal behavior and their relationship to specific cultural constructs would be of interest.

  11. Reduction in young male suicide in Scotland

    OpenAIRE

    Stark, Cameron; Stockton, Diane; Henderson, Rob

    2008-01-01

    Abstract Background Rates of suicide and undetermined death increased rapidly in Scotland in the 1980's and 1990's. The largest increases were in men, with a marked increase in rates in younger age groups. This was associated with an increase in hanging as a method of suicide. National suicide prevention work has identified young men as a priority group. Routinely collected national information suggested a decrease in suicide rates in younger men at the beginning of the 21st century. This stu...

  12. Policy and governance to address depression and suicide in Bhutan: The national suicide-prevention strategy.

    Science.gov (United States)

    Dorji, Gampo; Choki, Sonam; Jamphel, Kinga; Wangdi, Yeshi; Chogyel, Tandin; Dorji, Chencho; Nirola, Damber Kumar

    2017-04-01

    Suicide and mental disorders are a growing public health issue in Bhutan, due in part to a rapidly transitioning society. The burden of suicide has been recognized by the Royal Government of Bhutan and, as a result, it introduced the country's first ever national suicide-prevention plan in 2015. The 3-year action plan takes a holistic approach to making suicide-prevention services a top social priority, through strengthening suicide-prevention policies, promoting socially protective measures, mitigating risk factors and reaching out to individuals who are at risk of suicide or affected by incidents of suicide. This article documents Bhutan's policy and governance for addressing depression and suicide within the context of its national suicide-prevention strategy, examines progress and highlights lessons for future directions in suicide prevention. Since the endorsement of the 3-year action plan by the prime minister's cabinet, the implementation of suicide-prevention measures has been accelerated through a high-level national steering committee. Activities include suicide-prevention actions by sectors such as health, education, monastic communities and police; building capacity of gatekeepers; and improving the suicide information system to inform policies and decision-making. Suicide-prevention activities have become the responsibility of local governments, paving the way for suicide prevention as an integral mandate across sectors and at grass-root levels in the Kingdom of Bhutan.

  13. [Suicidal behaviour and attempted suicide occurring during assessment by the outreach psychiatric emergency service].

    Science.gov (United States)

    de Winter, R F P; de Groot, M H; van Dassen, M; Deen, M L; de Beurs, D P

    The outreach emergency psychiatric service plays an important role in recognising, arranging interventions and preventing suicide and suicidal behaviour. However, little is known about the assessments that members of the emergency team make when faced with patients showing suicidal behaviour. AIM: To describe the relationships that are revealed between patient characteristics, suicidal thoughts and attempted suicide during assessments made by the emergency psychiatric service in The Hague. METHOD: The emergency service kept a detailed record of 14,705 consultations. We compared the characteristics of patients who had suicidal thoughts with those of patients who had no such thoughts and we also compared the characteristics of patients who had attempted to commit suicide with those of patients who had not. We drew these comparisons by using logistic regression models, adjusting for clustering. RESULTS: 32.2% of the patients showed signs of suicidal behaviour and 9.2 % appeared likely to attempt suicide. Suicidal behaviour occurred most often in patients with depression. Suicidal patients were more often admitted to hospital than were non-suicidal patients and they were more likely to have been referred by a general practitioner or a general hospital. Medication was the most frequent means employed in attempts to commit suicide. CONCLUSION: In about one third of the consultations of the outreach emergency psychiatric service, the patient showed suicidal behaviour. The actions and the policy of the emergency psychiatric service with regard to suicidal behaviour were diverse and dependent on factors that could change over the course of time.

  14. Temperaments in completed suicides: Are they different from those in suicide attempters and controls?

    Science.gov (United States)

    Pompili, Maurizio; Innamorati, Marco; Milelli, Mariantonietta; Battuello, Michele; Erbuto, Denise; Lester, David; Gonda, Xenia; Rihmer, Zoltan; Amore, Mario; Girardi, Paolo

    2016-02-01

    Temperaments in completed suicides have never been assessed whereas there is substantial research on temperaments in attempted suicides and psychiatric patients. The significant others of 18 completed suicides participated in this study in order to provide an assessment of temperaments, hopelessness, depression and the suicide risk of their loved ones. The data were compared with data from 244 psychiatric patients of whom 83 had attempted suicide in the previous month. The following instruments were used: the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A), the Beck Hopelessness Scale (BHS), the Gotland Scale for Male Depression (GSMD), and the Mini International Neuropsychiatric Interview (MINI) module for assessing suicide risk. Individuals who died by suicide more frequently had scores of 9 or higher on the BHS and higher MINI suicide risk scores compared with patients with mood disorders who had not attempted suicide in the previous month. Completed suicides also had lower scores on the TEMPS-A Cyclothymia and Anxiety scales and on the MINI suicide risk scale than mood disorder patients with a recent suicide attempt. Proxy assessment of variables through survivors can result in underestimation of psychiatric morbidity and other parameters investigated, and limits the generalization of our results Our study adds information about temperamental subtypes and other variables in completed suicides and points to their difference from attempted suicides and non-suicidal psychiatric patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The impact of media reporting of suicide on actual suicides in Taiwan, 2002-05.

    Science.gov (United States)

    Chen, Ying-Yeh; Chen, Feng; Yip, Paul S F

    2011-10-01

    To assess changes in the intensity of suicide news reporting in Taiwan's local newspapers after the arrival of a daily tabloid-type newspaper, Apple Daily (AD), and evaluate the impact of suicide news reporting on actual suicides and possible mutual causation. A counting process was used to estimate the intensity of daily suicide news items reported in the China Times (CT) and United Daily (UD) before and after the arrival of AD (2002-05). Poisson regression models were used to assess the impact of the intensity of suicide news reporting on the actual number of next day suicides. Granger's causation model was used to assess mutual causation between suicide news reporting and actual suicides. There was a significant increase in reporting intensity of suicide news in the UD soon after the entry of the AD into Taiwan's media market, while a delayed increase of approximately 1 year was observed in the CT. After the arrival of the AD, the reporting intensity in the UD was significantly related to the occurrence of actual suicides (psuicide news reporting and actual suicides was also observed. The presence of the AD in Taiwan has fuelled competitive reporting of suicide news among traditional newspapers. This increase in the intensity of suicide news reporting has consequently had an impact on the actual number of suicides. This provides further empirical support for improving media reporting as a key element in suicide prevention.

  16. Predictors of suicides occurring within suicide clusters in Australia, 2004-2008.

    Science.gov (United States)

    Derek Cheung, Yee Tak; Spittal, Matthew J; Williamson, Michelle Kate; Tung, Sui Jay; Pirkis, Jane

    2014-10-01

    A number of studies have investigated the presence of suicide clusters, but few have sought to identify risk and protective factors of a suicide occurring within a cluster. We aimed to identify socio-demographic and contextual characteristics of suicide clusters from national and regional analyses of suicide clusters. We searched the National Coroners Information System for all suicides in Australia from 2004 to 2008. Scan statistics were initially used to identify those deaths occurring within a spatial-temporal suicide cluster during the period. We then used logistic regression and generalized estimation equations to estimate the odds of each suicide occurring within a cluster differed by sex, age, marital status, employment status, Indigenous status, method of suicide and location. We identified 258 suicides out of 10,176 suicides during the period that we classified as being within a suicide cluster. When the deceased was Indigenous, living outside a capital city, or living in the northern part of Australia (in particular, Northern Territory, Queensland and Western Australia) then there was an increased likelihood of their death occurring within a suicide cluster. These findings suggest that suicide clustering might be linked with geographical and Indigenous factors, which supported sociological explanations of suicide clustering. This finding is significant for justifying resource allocation for tackling suicide clustering in particular areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Psychological strains and suicide intent: Results from a psychological autopsy study with Chinese rural young suicides.

    Science.gov (United States)

    Sun, Long; Li, Han; Zhang, Jie; Wu, Qiong

    2015-11-01

    Previous studies have examined the prevalence of psychological strains among various suicide populations. However, it is still unexamined whether psychological strains can predict suicide intent directly. We planned to explore the prevalence of psychological strains and analyze the relationship between psychological strains and suicide intent among Chinese rural young suicides. Psychological autopsy method was used to investigate the environmental and other factors of rural young suicides. Psychological strains were identified from in-depth interviews by the proxy informants of each suicide. The first 8 items of Beck's Suicidal Intention Scale (SIS) were used to estimate the suicide intent. Results showed that 96.6% of the suicides had at least one type of strain, and those suicides who had more strains tended to score higher on the suicide intent scale. The study further supports that suicide intent can be predicted by psychological strains in Chinese rural young suicides. The scanning of psychological strains can be used for suicide prevention in Chinese rural young suicides. © The Author(s) 2015.

  18. Gender differences in suicide and suicide attempts among US Army soldiers.

    Science.gov (United States)

    Maguen, Shira; Skopp, Nancy A; Zhang, Ying; Smolenski, Derek J

    2015-02-28

    In order to best tailor suicide prevention initiatives and programs, it is critical to gain an understanding of how service members׳ suicide risk factors may differ by gender. We aimed to better understand gender differences in suicide and suicide attempts among soldiers, including demographic, military, mental health, and other risk factors. We also examined risk factors uniquely associated with suicide and suicide attempts. We conducted a retrospective study of 1857 US Army soldiers who died by suicide or attempted suicide between 2008 and 2010 and had a Department of Defense Suicide Event Report. Female and male soldiers had more similarities than differences when examining risk factors associated with suicide. The only gender difference approaching significance was workplace difficulties, which was more strongly associated with suicide for female soldiers, compared to their male counterparts. Among suicide decedents, the most common risk factor was having a failed intimate relationship in the 90 days prior to suicide. Among those who attempted suicide, the most common risk factor was a major psychiatric diagnosis. Better understanding both gender differences and risk factors uniquely associated with suicide has critical prevention and public health implications as we work to better understand preventable mortality in our youngest generation of service members. Published by Elsevier Ireland Ltd.

  19. Suicidal Ideation in Anxiety-Disordered Youth

    Science.gov (United States)

    O'Neil, Kelly A.; Puleo, Connor M.; Benjamin, Courtney L.; Podell, Jennifer L.; Kendall, Philip C.

    2012-01-01

    Evidence is mixed regarding an independent association between anxiety and suicidality in youth. Study 1 examined suicidal ideation in treatment-referred, anxiety-disordered youth (N = 312, aged 7-17). Forty-one percent of anxiety-disordered youth endorsed suicidal ideation. Anxiety disorder severity, global impairment, and current depressive…

  20. Borderline personality disorder in suicidal adolescents.

    Science.gov (United States)

    Yen, Shirley; Gagnon, Kerry; Spirito, Anthony

    2013-05-01

    The diagnosis of borderline personality disorder (BPD) in adolescents has been controversial. Thus, few studies have examined BPD in suicidal adolescents, even though it is strongly associated with suicidal behaviours in adults. This study examines differences between suicidal adolescents with (n = 47) and without (n = 72) BPD on history and characteristics of suicidal behaviour, Axis I co-morbidity, affect regulation and aggression. Assessments were completed with both adolescents and parents, and consensus ratings based on best available data were analysed. BPD participants were more likely to have a history of suicide attempts and to have been admitted because of a suicide attempt (vs. suicidal ideation). There were no significant differences in self-injurious behaviours or degree of suicidal ideation. BPD participants also had more psychiatric co-morbidity and higher aggression scores but no significant differences in affective dysregulation compared with suicidal adolescents without BPD. Diagnostic stability over 6 months was modest. Our results demonstrate that, compared with other acutely suicidal adolescents, the clinical profile of BPD participants is unique and suggests an increased risk for suicidal behaviours. This extends upon other studies that support the construct validity of BPD during adolescence and suggests that BPD should be considered in suicide risk assessment for adolescents. Copyright © 2012 John Wiley & Sons, Ltd.

  1. The use of technology in suicide prevention

    NARCIS (Netherlands)

    Boonstra, T.W.; Larsen, M.E.; Cummins, N.; O'Dea, B.; Tighe, J.; Nicholas, J.; Shand, F.; Epps, J.; Christensen, H.

    2015-01-01

    Suicide is one of the leading causes of death globally, and is notably a significant cause of death amongst young people. A suicide outcome is a complex combination of personal, social, and health factors, and therefore suicide prevention is a challenge, requiring a systems approach incorporating

  2. Suicide Prevention with Diverse College Students

    Science.gov (United States)

    Shadick, Richard; Akhter, Sarah

    2014-01-01

    Because of a dearth of experience in preventing suicide in diverse student populations, Pace University developed a multicultural suicide prevention kit. This article details the process used to develop the kit. The rationale for approaching suicide prevention in a culturally competent manner is presented, and methods used to gain culture-specific…

  3. Traumatic Stress as a Predictor of Suicidality

    Science.gov (United States)

    Todd, Sherry Malana

    2009-01-01

    Suicide is a deliberate act of annihilation against one's self due to a crisis of problem solving. Far too many youth are dying by their own hands resulting in suicide being the third leading cause of death for 10-19 year olds (CDC, 2005). Suicide is particularly problematic for adolescents due to the impulsivity inherent in adolescent…

  4. Getting Real about Suicide Prevention in Schools

    Science.gov (United States)

    Schiro, Theodora

    2018-01-01

    After her son died by suicide, Theodora Schiro vowed to raise awareness and teach others about depression and suicide. In this article, Schiro (a former teacher and principal) explains how educators can detect warning signs, devise preventative programs, and fight the stigma associated with suicide.

  5. Reflections on Jokes and Cartoons about Suicide

    Science.gov (United States)

    Lester, David

    2012-01-01

    This article is intended to engage others in a dialogue about the role and meaning of jokes about suicide. Types of jokes involving suicide are examined to distinguish the different types of humor involved. A sample of 118 recent political cartoons in an online website was downloaded, of which 73 concerned suicide bombers. Examples of suicide…

  6. Crucial elements in suicide prevention strategies

    DEFF Research Database (Denmark)

    Nordentoft, Merete

    2011-01-01

    on restrictions in firearms and carbon monoxide gas. At the selective prevention level, a review of risk of suicide in homelessness and schizophrenia and risk factors for suicide in schizophrenia is conducted and possible interventions are mentioned together with the evidence for their effect. Suicide rate...

  7. Nonresident Suicides in England: A National Study

    Science.gov (United States)

    Windfuhr, Kirsten; Bickley, Harriet; While, David; Williams, Alyson; Hunt, Isabelle M.; Appleby, Louis; Kapur, Navneet

    2010-01-01

    Little is known about the numbers and characteristics of people who travel away from home before dying by suicide. Therefore, this studied attempts to identify the sociodemographic characteristics, location, and method of suicide in people who died distant from home, in a national sample. Data were collected on all English suicides and a patient…

  8. Youth Suicide and Guns. Firearm Facts.

    Science.gov (United States)

    Duker, Laurie, Ed.

    Whether or not a suicide attempt results in death depends in large part on the method chosen. If a teenager attempts suicide with a gun, his or her death is nearly guaranteed. This brief fact sheet presents data on firearms and suicide, the third leading cause of death for adolescents and young adults in the United States. Any number of societal…

  9. College Students' Reasons for Concealing Suicidal Ideation

    Science.gov (United States)

    Burton Denmark, Adryon; Hess, Elaine; Becker, Martin Swanbrow

    2012-01-01

    Self-reported reasons for concealing suicidal ideation were explored using data from a national survey of undergraduate and graduate students: 558 students indicated that they seriously considered attempting suicide during the previous year and did not tell anyone about their suicidal thoughts. Content analysis of students' qualitative responses…

  10. Posttraumatic stress disorder diagnostic criteria and suicidal ...

    African Journals Online (AJOL)

    Objective: Exposure to traumatic events may precipitate suicidal ideation. Once an individual is diagnosed with PTSD, a suicide risk assessment often follows. This study explores how PTSD symptom criteria correlate with suicidal ideation in a sample of police officers. While the psychometric measures of PTSD often mirror ...

  11. Inter-regional variations in suicide rates.

    Science.gov (United States)

    Jagodic, Helena Korosec; Agius, Mark; Pregelj, Peter

    2012-09-01

    Suicidal behaviour is a significant public health problem. Suicide alone represents the 10th leading cause of death worldwide. Suicide is a complex phenomenon and may be the result of an interaction of biological, psychological and socioeconomic factors. Although there are many differences in suicide rates between different countries in the world, some studies reported huge differences of suicide rates between different regions within the same country as well. The studies that investigated the regional differences in suicide rates were gathered in the present article. The studies revealed that depression frequently remained unidentified and thus untreated and could contribute to high regional suicide rates. It could be speculated that access to services, which increases the possibility of diagnosis and treatment of mental disorders, could have an impact on regional suicide rates. Thus the availability of services may be relevant in explaining geographical variations in suicide incidence. Many studies reported that suicide was a major public health issue of particular concern among rural populations, which experienced a consistently higher suicide rate than urban areas considering the availability of psychiatric services, was typically less available in rural regions. As suggested in some studies, it seems that socioeconomic factors outweighed climatic factors in explaining regional differences in the suicide rate but further research is needed.

  12. Suicidality in a Sample of Arctic Households

    Science.gov (United States)

    Haggarty, John M.; Cernovsky, Zack; Bedard, Michel; Merskey, Harold

    2008-01-01

    We investigated the association of suicidal ideation and behavior with depression, anxiety, and alcohol abuse in a Canadian Arctic Inuit community. Inuit (N = 111) from a random sample of households completed assessments of anxiety and depression, alcohol abuse, and suicidality. High rates of suicidal ideation within the past week (43.6%), and…

  13. Suicides in the Nazi Concentration Camps.

    Science.gov (United States)

    Ryn, Zdzislaw

    1986-01-01

    On the basis of psychiatric interviews with 69 former prisoners of the Auschwitz-Birkenau concentration camp, this paper describes the circumstances, motives, and ways of committing suicide in the camp. The interviews made it clear that thousands of prisoners perished by suicide. The number of committed suicides was larger than that of attempted…

  14. Inpatient suicide in a Chinese psychiatric hospital.

    Science.gov (United States)

    Li, Jie; Ran, Mao-Sheng; Hao, Yuantao; Zhao, Zhenhuan; Guo, Yangbo; Su, Jinghua; Lu, Huixian

    2008-08-01

    Little is known about the risk factors for suicide among psychiatric inpatients in China. In this study we identified the risk factors of suicide among psychiatric inpatients at Guangzhou Psychiatric Hospital. All psychiatric inpatients who died by suicide during the 1956-2005 period were included in this study. Using a case-control design, 64 inpatients with schizophrenia who died by suicide were compared with a matched 64 controls. The results indicate that the rate of suicide was 133.1/100,000 admissions (95%CI 103.4-162.9). There were no significant differences in the method, location, or time of suicide between male and female inpatients. The number of hospitalizations was significantly larger in the suicide group than that in the control group. In logistic regression analyses, guilty thought, depressive mood, and suicidal ideation and suicide attempt 1 month before hospital admission were identified as independent predictors of suicide among inpatients with schizophrenia. The findings of risk factors for schizophrenic inpatient suicide should be taken into account when developing interventions to prevent suicide among these patients.

  15. Suicide in South Asia: a scoping review

    NARCIS (Netherlands)

    Jordans, Mark J D; Kaufman, Anne; Brenman, Natassia; Adhikar, Ramesh; Luitel, Nagendra; Tol, Wietse; Komproe, Ivan|info:eu-repo/dai/nl/142349321

    2014-01-01

    Background Globally, suicide is an important cause of mortality. In low- and middle income settings, it is difficult to find unequivocal data to establish suicide rates. The objective of this review is to synthesize the reporting of suicide incidence in six south Asian countries. Methods We

  16. Bullying and suicidal behavior in jails.

    NARCIS (Netherlands)

    Blaauw, E.; Winkel, F.W.; Kerkhof, A.J.F.M.

    2001-01-01

    Relationships between bullying features and suicidal behavior of inmates were examined. The files of 95 suicide victims in jails and prisons in the Netherlands were examined for reports of bullying. In addition, 221 nonsuicidal jail inmates and 53 suicidal jail inmates were interviewed. The files of

  17. Risk Factors for Attempting Suicide in Prisoners

    Science.gov (United States)

    Sarchiapone, Marco; Carli, Vladimir; Di Giannantonio, Massimo; Roy, Alec

    2009-01-01

    We wished to examine determinants of suicidal behavior in prisoners. 903 male prisoners had a psychiatric interview which included various psychometric tests. Suicide attempters were compared with prisoners who had never attempted suicide. Significantly more of the attempters had a history of psychiatric disorder, substance abuse, a family history…

  18. Sexual Orientation in Adolescents Who Commit Suicide.

    Science.gov (United States)

    Shaffer, David; And Others

    1995-01-01

    Examined relationship between suicidal behavior and homosexuality in adolescence in an unselected, matched sample. Found no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support. (JBJ)

  19. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  20. Suicide in older adults: the role of emotions and cognition.

    Science.gov (United States)

    Kiosses, Dimitris N; Szanto, Katalin; Alexopoulos, George S

    2014-11-01

    Suicide in older adults is a significant clinical concern. In this review of recent findings, we concentrate on the role of emotions and cognition in suicide risk and behavior in older adults. We discuss the epidemiology of suicide in older adults, integrate recent findings on non-psychotic major depression, schizophrenia and suicidal ideation, explore the relationship of emotion regulation with suicide, present recent advances on suicide in demented patients, and describe the latest developments on cognition and decision processes in suicide.