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Rodolfo Savica, Brandon R Grossardt, James H Bower, J Eric Ahlskog, Michelle M Mielke, Walter A Rocca
BACKGROUND: Epidemiological studies of drug-induced parkinsonism remain limited. OBJECTIVES: To investigate the incidence and time trends of drug-induced parkinsonism over 30 years in a geographically defined American population. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to identify all persons in Olmsted County, Minnesota, who received a screening diagnostic code for parkinsonism from 1976 through 2005...
October 25, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Amanda J Sales, Vinícius A Hiroaki-Sato, Sâmia R L Joca
Systemic or hippocampal administration of nitric oxide (NO) synthase inhibitors induces antidepressant-like effects in animals, implicating increased hippocampal levels of NO in the neurobiology of depression. However, the role played by different NO synthase in this process has not been clearly defined. As stress is able to induce neuroinflammatory mechanisms and trigger the expression of inducible nitric oxide synthase (iNOS) in the brain, as well as upregulate neuronal nitric oxide synthase (nNOS) activity, the aim of the present study was to investigate the possible differential contribution of hippocampal iNOS and nNOS in the modulation of the consequences of stress elicited by the forced swimming test...
October 24, 2016: Behavioural Pharmacology
Kinda Fattouh, Diane Collet-Benzaquen, Anne M Provensal, Françoise Desseigne, Christine Castillo, Patrick Combemale, Arnaud de la Fouchardière
Necrotizing Infundibular Crystalline Folliculitis (NICF) is rare entity of unknown pathogenesis presenting as follicular crystalline papules arising in seborrheic areas. We report 2 cases of NICF in patients under targeted therapy for metastatic adenocarcinoma. In one case, the lesions reappeared cyclically every 3 weeks after each injection and in the other case, lesions persisted until disruption of the continuous oral therapy. Punch-biopsies demonstrated folliculitis with a plugging crystalline material associated with either bacteria or yeast...
September 27, 2016: American Journal of Dermatopathology
Kerry Anne Rambaran, Charles F Seifert
Drug-induced interstitial lung disease is a rare condition attributed to several medications, including antimicrobial agents such as amphotericin B, anti-inflammatory agents such as methotrexate, biologic agents such as bevacizumab, and cardiovascular agents and chemotherapeutic agents. We describe the case of a 73-year-old female who developed interstitial lung disease following chronic use of nitrofurantoin for a urinary tract infection (UTI). The patient was taking nitrofurantoin 100 mg capsules twice daily for approximately 3 years...
December 2016: Drug Saf Case Rep
Nehal Narayan, Shirley Rigby, Francesco Carlucci
Sulfasalazine has long been used for the treatment of rheumatoid arthritis and is often chosen as a first-line treatment. Here, we report a case of sulfasalazine-induced autoimmune thrombocytopenia and review the mechanisms behind drug-induced immune thrombocytopenia (DITP) and the approach to its diagnosis and management.
October 24, 2016: Clinical Rheumatology
Jonathan G Stine, Jennifer Wang, Brian W Behm
Drug-induced liver injury is a rare but clinically important diagnosis. Vedolizumab is an α4β7 integrin inhibitor recently approved for use in patients with moderate-to-severe inflammatory bowel disease. Cases of hepatoxicity due to vedolizumab in the pre-marketing stage were rare, and all cases resolved upon drug withdrawal. We present here the first reported case of hepatotoxicity attributable to vedolizumab, which despite drug cessation persisted with chronic cholestatic liver injury.
September 28, 2016: Journal of Clinical and Translational Hepatology
Paola De Cicco, Elisabetta Panza, Giuseppe Ercolano, Chiara Armogida, Giuseppe Sessa, Giuseppe Pirozzi, Giuseppe Cirino, John L Wallace, Angela Ianaro
Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs). They consist of a traditional NSAID to which an H2S-releasing moiety is covalently attached. We have recently demonstrated that H2S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H2S-releasing derivative of naproxen, ATB-346 [2-(6- methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H2S...
October 21, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Takashi Tomita, Hidekazu Goto, Kenji Sumiya, Tadashi Yoshida, Katsuya Tanaka, Yukinao Kohda
Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose...
November 30, 2016: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
Kun Qian, Christoph Janott, Vedhas Pandit, Zixing Zhang, Clemens Heiser, Winfried Hohenhorst, Michael Herzog, Werner Hemmert, Bjoern Schuller
OBJECTIVE: Obstructive Sleep Apnea (OSA) is a serious chronic disease and a risk factor for cardiovascular diseases. Snoring is a typical symptom of OSA patients. Knowledge of the origin of obstruction and vibration within the upper airways is essential for a targeted surgical approach. Aim of this paper is to systematically compare different acoustic features, and classifiers for their performance in the classification of the excitation location of snore sounds. METHODS: Snore sounds from 40 male patients have been recorded during Drug-Induced Sleep Endoscopy, and categorized by ENT experts...
October 21, 2016: IEEE Transactions on Bio-medical Engineering
Christopher Goldring, Daniel J Antoine, Frank Bonner, Jonathan Crozier, Chris Denning, Robert J Fontana, Neil A Hanley, David C Hay, Magnus Ingelman-Sundberg, Satu Juhila, Neil Kitteringham, Beatriz Silva-Lima, Alan Norris, Chris Pridgeon, James A Ross, Rowena Sison Young, Danilo Tagle, Belen Tornesi, Bob van de Water, Richard J Weaver, Fang Zhang, B Kevin Park
Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalised toxicology to determine inter-individual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury (DILI) means that no current single cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human DILI...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hidenori Kamiguchi, Mika Murabayashi, Ikuo Mori, Akira Horinouchi, Kazutaka Higaki
CONTEXT: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment, and non-invasive diagnostic tool is highly desirable. OBJECTIVE: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach. METHOD: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs. RESULTS: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose dependent manners; and it was well correlated with histopathological observation...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Tiffany Elizabeth Cho, Jack Uetrecht
Little is known with certainty about the mechanisms of idiosyncratic drug reactions (IDRs); however, there is substantive evidence that reactive metabolites are involved in most, but not all, IDRs. In addition, evidence also suggests that most IDRs are immune mediated. That raises the question of how reactive metabolites induce an immune response that can lead to an IDR. The dominant hypotheses are the hapten and danger hypotheses. These are complementary hypotheses: a reactive metabolite can act as a hapten to produce neoantigens, and it can also cause cell damage leading to the release of danger-associated molecular pattern molecules that activate antigen presenting cells...
October 24, 2016: Chemical Research in Toxicology
Hui Liu, Fan Zhang, Shital Kumar Mishra, Shuigeng Zhou, Jie Zheng
Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data...
October 24, 2016: Scientific Reports
Qian Sun, Patricia Loughran, Richard Shapiro, Indira H Shrivastava, Daniel J Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R Billiar, Melanie J Scott
: Sterile liver inflammation, such as liver ischemia reperfusion, hemorrhagic shock after trauma and drug-induced liver injury is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here we identify a novel mechanism for redox-mediated regulation of AIM2-inflammasome activation in hepatocytes after redox stress in mice, which occurs via interaction with cytosolic HMGB1. We show that in liver during hemorrhagic shock in mice, and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Keren Bachi, Salvador Sierra, Nora D Volkow, Rita Z Goldstein, Nelly Alia-Klein
Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality...
February 2017: Current Opinion in Behavioral Sciences
Felix Royo, Laura Palomo, Justyna Mleczko, Esperanza Gonzalez, Cristina Alonso, Ibon Martínez, Miriam Pérez-Cormenzana, Azucena Castro, Juan M Falcon-Perez
Hepatocytes are involved in the endogenous and drug metabolism; many of the enzymes involved in those processes are incorporated into extracellular vesicles and secreted into the bloodstream. Liver-damaging conditions modify the molecular cargo of those vesicles significantly. However, no information about the effect of these hepatic vesicles on the extracellular environment is available. Drug-induced liver damage increases the number of circulating extracellular vesicles and affects the release and content of hepatocyte-derived vesicles...
October 19, 2016: European Journal of Pharmaceutical Sciences
Madhusudanarao Vuda, Ashwin Kamath
Several commonly used medications impair mitochondrial function resulting in adverse effects or toxicities. Drug induced mitochondrial dysfunction may be a consequence of increased production of reactive oxygen species, altered mitochondrial permeability transition, impaired mitochondrial respiration, mitochondrial DNA damage or inhibition of beta-oxidation of fatty acids. The clinical manifestation depends on the specific drug and its effect on mitochondria. Given the ubiquitous presence of mitochondria and its central role in cellular metabolism, drug-mitochondrial interactions may manifest clinically as hepatotoxicity, enteropathy, myelosuppression, lipodystrophy syndrome or neuropsychiatric adverse effects, to name a few...
October 19, 2016: Mitochondrion
A D B Vliegenthart, R A Kimmitt, J H Seymour, N Z Homer, J I Clarke, M Eddleston, A Gray, D M Wood, P I Dargan, J G Cooper, D J Antoine, D J Webb, S C Lewis, D N Bateman, J W Dear
: Acetaminophen (paracetamol-APAP) is the commonest cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analysed from discovery (N=116) and validation (N=150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI...
October 22, 2016: Clinical Pharmacology and Therapeutics
Norimitsu Shirai, Frank J Geoly, Walter F Bobrowski, Carlin Okerberg
Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies in cells exposed to xenobiotics. Demonstration of the lamellar bodies by transmission electron microscopy (TEM) is the hallmark for a definitive diagnosis of phospholipidosis. However, the preparation of tissue samples for TEM and their ultrastructural evaluation are technically challenging and time consuming. Paraphenylenediamine (PPD) is essentially a fat stain, and the staining mechanism is based upon the osmication of unsaturated lipids...
October 21, 2016: Toxicologic Pathology
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
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