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Drug-induced suicide

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https://www.readbyqxmd.com/read/29099485/caspase-10-a-molecular-switch-from-cell-autonomous-apoptosis-to-communal-cell-death-in-response-to-chemotherapeutic-drug-treatment
#1
Andrea Mohr, Laura Deedigan, Sylwia Jencz, Yasamin Mehrabadi, Lily Houlden, Stella-Maris Albarenque, Ralf M Zwacka
The mechanisms of how chemotherapeutic drugs lead to cell cycle checkpoint regulation and DNA damage repair are well understood, but how such signals are transmitted to the cellular apoptosis machinery is less clear. We identified a novel apoptosis-inducing complex, we termed FADDosome, which is driven by ATR-dependent caspase-10 upregulation. During FADDosome-induced apoptosis, cFLIPL is ubiquitinated by TRAF2, leading to its degradation and subsequent FADD-dependent caspase-8 activation. Cancer cells lacking caspase-10, TRAF2 or ATR switch from this cell-autonomous suicide to a more effective, autocrine/paracrine mode of apoptosis initiated by a different complex, the FLIPosome...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29064136/pyridoxamine-a-novel-treatment-for-schizophrenia-with-enhanced-carbonyl-stress
#2
Masanari Itokawa, Mitsuhiro Miyashita, Makoto Arai, Takashi Dan, Katsuyoshi Takahashi, Taro Tokunaga, Kayo Ishimoto, Kazuya Toriumi, Tomoe Ichikawa, Yasue Horiuchi, Akiko Kobori, Satoshi Usami, Takeo Yoshikawa, Naoji Amano, Shinsuke Washizuka, Yuji Okazaki, Toshio Miyata
AIM: The aim of this clinical trial was to obtain proof of concept for high-dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. METHODS: Ten Japanese schizophrenia patients with high plasma pentosidine, which is a representative biomarker of enhanced carbonyl stress, were recruited in a 24 week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was administered using a conventional anti-psychotic regimen...
October 24, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29032023/social-determinants-of-drug-related-mortality-in-a-general-population
#3
Sanna Rönkä, Karoliina Karjalainen, Pekka Martikainen, Pia Mäkelä
BACKGROUND: We investigated the association between social determinants and a broad selection of drug-related deaths in a general population. METHODS: We conducted a follow-up of an 11% random sample of working-age Finnish residents for 1996-2007 linked with an oversampling of deaths and population registration data on social characteristics. We defined total drug-related deaths as those from psychoactive substance use disorders and drug-induced poisonings (drug-induced deaths) as well as drug-related accidents, homicides, illnesses, and suicides...
October 4, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28950817/specific-patient-features-affect-antiepileptic-drug-therapy-decisions-focus-on-gender-age-and-psychiatric-comorbidities
#4
Pisani Laura Rosa, Nikanorova Marina, Johannessen Landmark Cecilie, Johannessen Svein Ivar, Pisani Francesco
BACKGROUND: Patient features, apart from the type of seizues/epilepsy, affect markedly antiepileptic drug (AED) choice and dosage. The present review focuses on gender, age and psychiatric comorbidities which play a leading role in influencing antiepileptic treatment. METHODS: Reviews with large population of patients, controlled clinical trials, observational investigations, experimental studies and experimental reviews of experimental data, where appropriated, were analysed and illustrated to produce the most homogeneous indications possible...
September 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28924362/identification-and-characteristics-of-time-related-shifts-in-suicide-related-event-frequency-during-smoking-cessation-treatment-with-varenicline
#5
Hayato Akimoto, Haruna Wakiyama, Shinji Oshima, Akio Negishi, Kousuke Ohara, Sachihiko Numajiri, Mitsuyoshi Okita, Shigeru Ohshima, Naoko Inoue, Daisuke Kobayashi
Objectives: To survey time-related shifts in number of suicide-related events (SRE) during smoking cessation treatment with varenicline (VAR) in cases from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), as well as the characteristics of these shifts. Methods: We isolated cases from the FAERS database involving VAR usage where SRE was reported as an adverse event (SRE+/VAR+ case) and established a histogram of SRE+/VAR+ case numbers per week. Furthermore, we focused on "cases reporting specific adverse events prior to drug usage start" using X-bar and R chart concepts...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28878698/synthetic-cathinone-and-cannabinoid-designer-drugs-pose-a-major-risk-for-public-health
#6
REVIEW
Aviv M Weinstein, Paola Rosca, Liana Fattore, Edythe D London
As part of an increasing worldwide use of designer drugs, recent use of compounds containing cathinones and synthetic cannabinoids is especially prevalent. Here, we reviewed current literature on the prevalence, epidemiology, bio-behavioral effects, and detection of these compounds. Gender differences and clinical effects will also be examined. Chronic use of synthetic cathinone compounds can have major effects on the central nervous system and can induce acute psychosis, hypomania, paranoid ideation, and delusions, similar to the effects of other better-known amphetamine-type stimulants...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28855574/genetic-studies-in-mice-directly-link-oocytes-produced-during-adulthood-to-ovarian-function-and-natural-fertility
#7
Ning Wang, Chonthicha Satirapod, Yasuyo Ohguchi, Eun-Sil Park, Dori C Woods, Jonathan L Tilly
Multiple labs have reported that mammalian ovaries contain oogonial stem cells (OSCs), which can differentiate into oocytes that fertilize to produce offspring. However, the physiological relevance of these observations to adult ovarian function is unknown. Here we performed targeted and reversible ablation of premeiotic germ cells undergoing differentiation into oocytes in transgenic mice expressing the suicide gene, herpes simplex virus thymidine kinase (HSVtk), driven by the promoter of stimulated by retinoic acid gene 8 (Stra8), a germ cell-specific gene activated during meiotic commitment...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793283/trifluoperazine-induced-suicidal-erythrocyte-death-and-s-nitrosylation-inhibition-reversed-by-the-nitric-oxide-donor-sodium-nitroprusside
#8
Mehrdad Ghashghaeinia, Mauro Carlos Wesseling, Elena Ramos, Polina Petkova-Kirova, Sabrina Waibel, Elisabeth Lang, Rosi Bissinger, Kossai Alzoubi, Baerbel Edelmann, Zohreh Hosseinzadeh, Peter Dreischer, Azam Shahvaroughi-Farahani, Ulrich Mrowietz, Martin Köberle, Lars Kaestner, Ingolf Bernhardt, Antonio Martínez-Ruiz, Thomas Wieder, Florian Lang
BACKGROUND AND PURPOSE: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluoromethyl)-(10)H-phenothiazine dihydrochloride; TFP) may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and inhibited by nitric oxide (NO)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28731926/history-of-anaesthesia-the-ketamine-story-past-present-and-future
#9
Georges Mion
No abstract text is available yet for this article.
September 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28727740/genetically-engineered-suicide-gene-in-mesenchymal-stem-cells-using-a-tet-on-system-for-anaplastic-thyroid-cancer
#10
Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Liya Zhu, Ho Won Lee, Yong Hyun Jeon, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28694090/milnacipran-affects-mouse-impulsive-aggressive-and-depressive-like-behaviors-in-a-distinct-dose-dependent-manner
#11
Iku Tsutsui-Kimura, Yu Ohmura, Takayuki Yoshida, Mitsuhiro Yoshioka
Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively...
June 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28687184/paraflocculus-plays-a-role-in-salicylate-induced-tinnitus
#12
Yali Du, Junxiu Liu, Qin Jiang, Qingchuan Duan, Lanqun Mao, Furong Ma
Tinnitus impairs quality of life of about 1-2% of the whole population. In most severe situation, tinnitus may cause social isolation, depression and suicide. Drug treatments for tinnitus are generally ineffective, and the mechanisms of tinnitus are still undetermined. Accumulating evidence suggests that tinnitus is related to changes of widespread brain networks. Recent studies propose that paraflocculus (PFL), which is indirectly connected to various cortical regions, may be a gating zone of tinnitus. So we examined the electrophysiological changes and neurotransmitter alterations of the PFL in a rat model of sodium salicylate (SS)-induced tinnitus...
June 29, 2017: Hearing Research
https://www.readbyqxmd.com/read/28676343/treatment-of-acute-myeloid-leukemia-with-t-cells-expressing-chimeric-antigen-receptors-directed-to-c-type-lectin-like-molecule-1
#13
Haruko Tashiro, Tim Sauer, Thomas Shum, Kathan Parikh, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Premal Lulla, Cliona M Rooney, Stephen Gottschalk, Malcolm K Brenner
The successful immunotherapy of acute myeloid leukemia (AML) has been hampered because most potential antigenic targets are shared with normal hematopoietic stem cells (HSCs), increasing the risk of sustained and severe hematopoietic toxicity following treatment. C-type lectin-like molecule 1 (CLL-1) is a membrane glycoprotein expressed by >80% of AML but is absent on normal HSCs. Here we describe the development and evaluation of CLL-1-specific chimeric antigen receptor T cells (CLL-1.CAR-Ts) and we demonstrate their specific activity against CLL-1(+) AML cell lines as well as primary AML patient samples in vitro...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28623497/-psychiatric-emergencies
#14
F Schneider, S Weber-Papen
Psychiatric emergencies present a frequent and interdisciplinary challenge. Clinical diagnosis and management are complicated by the acuity, and the patient's compliance is often limited by the illness. Psychiatric emergencies include states of acute agitation, suicidality, delirium, stupor, and drug-induced emergencies. Sometimes interventions such as conversational contact, responding empathically to patients, or "talking down" are sufficient. If pharmacotherapy is necessary, benzodiazepines and antipsychotic drugs are the primary agents of choice...
July 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#15
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16(Ink4a)-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28542880/suicidal-death-of-erythrocytes-in-cancer-and-its-chemotherapy-a-potential-target-in-the-treatment-of-tumor-associated-anemia
#16
REVIEW
Elisabeth Lang, Rosi Bissinger, Syed M Qadri, Florian Lang
In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca2+ -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4...
October 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28542233/is-survival-improved-by-the-use-of-niv-and-peg-in-amyotrophic-lateral-sclerosis-als-a-post-mortem-study-of-80-als-patients
#17
Christian Burkhardt, Christoph Neuwirth, Andreas Sommacal, Peter M Andersen, Markus Weber
BACKGROUND: Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown. OBJECTIVE: To investigate the effect of NIV and PEG on survival and causes of death in ALS patients. METHODS: Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015...
2017: PloS One
https://www.readbyqxmd.com/read/28526869/blocking-of-carnitine-palmitoyl-transferase-1-potently-reduces-stress-induced-depression-in-rat-highlighting-a-pivotal-role-of-lipid-metabolism
#18
Anne Skøttrup Mørkholt, Ove Wiborg, Jette G K Nieland, Søren Nielsen, John Dirk Nieland
Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#19
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255357/stat3-nf-%C3%AE%C2%BAb-regulated-lentiviral-tk-gcv-suicide-gene-therapy-for-cisplatin-resistant-triple-negative-breast-cancer
#20
Wei-Ying Kuo, Luen Hwu, Chun-Yi Wu, Jhih-Shian Lee, Chi-Wei Chang, Ren-Shyan Liu
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)...
2017: Theranostics
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