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Drug-induced suicide

Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
J Gibson Pennington, Jeffrey Guina
Eszopiclone is a benzodiazepine-like hypnotic that is commonly prescribed to treat insomnia. However, eszopiclone's efficacy has been questionable in several clinical trials, and its pharmacologic profile makes its effects on sleep and behavior difficult to predict. We report a case demonstrating an instance of eszopiclone-induced parasomnia involving paranoia and a suicide attempt in a patient taking eszopiclone. We explore possible biochemical explanations examining the pharmacologic profile of eszopiclone and its potential for drug-drug interactions, especially with concomitant administration of monoaminergic medications such as antidepressants...
September 2016: Innovations in Clinical Neuroscience
Abdulla Al Mamun Bhuyan, Elena Signoretto, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is utilized for the treatment of ALK positive non-small cell lung carcinoma. Side effects of the drug include decrease of blood hemoglobin concentration. Possible causes of anemia include stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases...
2016: Cellular Physiology and Biochemistry
Donald Paul Sullins
OBJECTIVE: To examine the links between pregnancy outcomes (birth, abortion, or involuntary pregnancy loss) and mental health outcomes for US women during the transition into adulthood to determine the extent of increased risk, if any, associated with exposure to induced abortion. METHOD: Panel data on pregnancy history and mental health history for a nationally representative cohort of 8005 women at (average) ages 15, 22, and 28 years from the National Longitudinal Study of Adolescent to Adult Health were examined for risk of depression, anxiety, suicidal ideation, alcohol abuse, drug abuse, cannabis abuse, and nicotine dependence by pregnancy outcome (birth, abortion, and involuntary pregnancy loss)...
2016: SAGE Open Medicine
S Gibiino, A Trappoli, B Balzarro, A R Atti, D De Ronchi
A 71-year-old man developed coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate extended release (XR) 20 g. At the time, he had been treated for bipolar depression with venlafaxine 75 mg/day, lamotrigine 100 mg/day, pregabalin 75 mg/day, and quetiapine XR 400 mg/day for approximately 1 year. Comorbidities were hypertension treated with metoprolol, diabetes mellitus type 2 treated with metformin, and benign prostatic hyperplasia treated with silodosin...
December 2015: Drug Safety—Case Reports
David J Laprade, Melissa S Brown, Morgan L McCarthy, James J Ritch, Nicanor Austriaco
The budding yeast Candida albicans is one of the most significant fungal pathogens worldwide. It proliferates in two distinct cell types: blastopores and filaments. Only cells that are able to transform from one cell type into the other are virulent in mouse disease models. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We now provide evidence that suggests that programmed cell death is cell-type specific in yeast: Filamentous C...
July 2016: Microbial Cell
F Lee Cantrell, Phyllis Mallett, Lenore Aldridge, Kimi Verilhac, Iain M McIntyre
Tapentadol (TAP) is an analgesic agent indicated for the management of different types of pain. It has a novel mechanism of action in that it induces analgesia via both μ-opioid receptor agonism and norepinephrine reuptake inhibition. Although deaths associated with TAP use have been reported, there is a paucity of published literature regarding TAP concentrations in biological samples obtained from TAP-associated fatalities. We report a case of TAP toxicity resulting in death with postmortem peripheral and central blood concentrations, liver, vitreous, urine, and gastric contents...
September 2016: Forensic Science International
Xiaoou Zhou, Malcolm K Brenner
Adoptive transfer of T cells can be an effective anticancer treatment. However, uncontrolled or unpredictable immediate or persistent toxic effects are a source of concern. The ability to conditionally eliminate aberrant cells in vivo is therefore becoming a critical step for the successful translation of this approach to the clinic. We review the evolution of safety systems, focusing on a suicide switch that can be expressed stably and efficiently in human T cells without impairing phenotype, function, or antigen specificity...
November 2016: Experimental Hematology
Udaya Ralapanawa, Kushalee Poornima Jayawickreme, Ekanayake Mudiyanselage Madhushanka Ekanayake, A M S Dhammika Menike Dissanayake
BACKGROUND: Sri Lanka has a high suicide rate, with more than 40 % of poisoning admissions due to overdose of drugs with Paracetamol being the commonest. Data regarding cardiotoxicity to paracetamol is very minimal though hepatotoxicity following poisoning is well studied. Paracetamol cardiotoxicity has rarely been clinically significant and may have well been overlooked. The possibility that paracetamol overdose might be directly cardiotoxic has been the subject of a few reports. Unexplained deaths and electrocardiographic changes associated with paracetamol poisoning have also been reported in which cardiac origin cannot be clearly ruled out...
2016: BMC Pharmacology & Toxicology
Thomas Peter, Rosi Bissinger, Elena Signoretto, Andreas F Mack, Florian Lang
BACKGROUND/AIMS: The antifungal drug Micafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. Side effects of Micafungin treatment include microangiopathic hemolytic anemia and thrombocytopenia with microvascular thrombosis. The development of thrombosis may be fostered by stimulation of eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
2016: Cellular Physiology and Biochemistry
Matthew D Hensley, Vikhyat S Bebarta, Douglas J Borys
OBJECTIVE: Significant adverse effects after acute pediatric methotrexate (MTX) exposures have been limited to parenteral exposures. Treatment recommendations for pediatric MTX exposures do not differentiate between routes of exposure. We report the incidence of significant clinical effects and drug-specific treatments reported in a large series of acute, pediatric MTX ingestions. METHODS: Poison center records of all MTX ingestions by patients younger than 17 years during 2000 to 2005 were collected from 6 poison centers...
October 2016: Pediatric Emergency Care
Yoshihiro Kusunoki, Daigo Nakazawa, Haruki Shida, Fumihiko Hattanda, Arina Miyoshi, Sakiko Masuda, Saori Nishio, Utano Tomaru, Tatsuya Atsumi, Akihiro Ishizu
Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis is a systemic small-vessel vasculitis, wherein, MPO-ANCA plays a critical role in the pathogenesis. Neutrophil extracellular traps (NETs) released from activated neutrophils are composed of extracellular web-like DNA and antimicrobial proteins, including MPO. Diverse stimuli, such as phorbol myristate acetate (PMA) and ligands of toll-like receptors (TLR), induce NETs. Although TLR-mediated NET formation can occur with preservation of living neutrophilic functions (called vital NETosis), PMA-stimulated neutrophils undergo cell death with NET formation (called suicidal NETosis)...
2016: Frontiers in Immunology
Reona Sakemura, Seitaro Terakura, Keisuke Watanabe, Jakrawadee Julamanee, Erina Takagi, Kotaro Miyao, Daisuke Koyama, Tatsunori Goto, Ryo Hanajiri, Tetsuya Nishida, Makoto Murata, Hitoshi Kiyoi
T cells genetically modified with a CD19 chimeric antigen receptor (CD19CAR) are remarkably effective against B-cell malignancies in clinical trials. However, major concerns remain regarding toxicities, such as hypogammaglobulinemia, due to B-cell aplasia or severe cytokine release syndrome after overactivation of CAR T cells. To resolve these adverse events, we aimed to develop an inducible CAR system by using a tetracycline regulation system that would be activated only in the presence of doxycycline (Dox)...
August 2016: Cancer Immunology Research
Naser Mozafari, Haleh Talaie, Simin Dokht Shoaei, Morteza Hashemian, Arezou Mahdavinejad
BACKGROUND: Body temperature is a critical criterion of health. Drugs and a variety of poisons can affect body temperature in poisoned patients, causing hyperthermia and hyperpyrexia. OBJECTIVES: Our previous study's findings in patients poisoned with organophosphate led us to the goal of this study: obtaining the initial tympanic temperature in patients poisoned by a variety of toxins. MATERIALS AND METHODS: A cross-sectional study reviewed the records of poisoned patients who were admitted to the toxicological intensive care unit (TICU) at Loghman Hakim hospital poison center (LHHPC) from February 2014 to February 2015...
April 2016: Iranian Red Crescent Medical Journal
Alexandra Rohracher, Francesco Brigo, Julia Höfler, Gudrun Kalss, Caroline Neuray, Judith Dobesberger, Giorgi Kuchukhidze, Markus Leitinger, Eugen Trinka
INTRODUCTION: The non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs. AREAS COVERED: Data sources included MEDLINE, EMBASE, Google Scholar and, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015)...
July 2016: Expert Opinion on Pharmacotherapy
Sabrina Waibel, Rosi Bissinger, Ghada Bouguerra, Salem Abbès, Florian Lang
The antiviral drug ritonavir has been shown to trigger suicidal death or apoptosis of tumour cells and has thus been considered for the treatment of malignancy. In analogy 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 Ca(2+) entry with increase in cytosolic Ca(2+) activity ([Ca(2+) ]i ), oxidative stress and ceramide...
July 2016: Basic & Clinical Pharmacology & Toxicology
A Appart, A-K Lange, I Sievert, F Bihain, D Tordeurs
INTRODUCTION: This paper exposes the complexity and discrete characteristic of the adjustment disorder with reference to its clinical and scientific diagnosis. Even though the disorder occurs in frequent clinical circumstances after important life events, such as mobbing, burn-out, unemployment, divorce or separation, pregnancy denial, surgical operation or cancer, the adjustment disorder is often not considered in the diagnosis since better known disorders with similar symptoms prevail, such as major depression and anxiety disorder...
May 20, 2016: L'Encéphale
Thomas Peter, Rosi Bissinger, Guilai Liu, Florian Lang
BACKGROUND/AIMS: The novel antifungal drug Anidulafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. The traditional antifungal drug amphotericin B has previously been shown to trigger eryptosis, the suicidal death of erythrocytes 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), oxidative stress, ceramide, activated protein kinase C (PKC), casein kinase 1α or p38 kinase and activated caspases...
2016: Cellular Physiology and Biochemistry
Qicheng Zhang, Zheng Liu, Jue Hou, Shuhui Wang, Chang Liu, Min Wei, Ying Liu, Yiming Shao
INTRODUCTION: Replication-competent vaccinia viruses (VACVs) show prolonged antigen expression time and greater stimulation of immune responses than their replication-incompetent counterparts. However, there is the potential risk of serious post-vaccination complications, especially for children and immunocompromised individuals, leading to safety concerns about the reintroduction of VACV as a vaccine vector. In this study, we improved the safety of the vaccinia virus TianTan (VACV-TT) based HIV vaccine by introducing the HSV-TK/GCV suicide gene system, which is composed of the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) and the antiviral drug ganciclovir (GCV)...
June 24, 2016: Vaccine
Szymon Kaczanowski
Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection...
2016: Physical Biology
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