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https://www.readbyqxmd.com/read/29684851/mitochondrial-dna-content-reduction-induces-aerobic-glycolysis-and-reversible-resistance-to-drug-induced-apoptosis-in-sw480-colorectal-cancer-cells
#1
Jing-Jing Mou, Jin Peng, Ying-Ying Shi, Na Li, You Wang, Yuan Ke, Yun-Feng Zhou, Fu-Xiang Zhou
Mutations and reductions in mitochondrial DNA (mtDNA), which are frequent in human tumors, may contribute to enhancing their malignant phenotypes. However, the effects of mtDNA abnormalities in colorectal cancer remain largely unknown. In this study, mtDNA-reduced cell model was established by partial depletion of mtDNA in SW480 cells and the effects of mtDNA reduction in colorectal cancer cells were investigated. We found that mtDNA-reduced cells had enhanced glucose uptake and generated markedly higher level of lactate...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29683955/successful-management-of-a-child-with-drug-induced-necrotizing-pancreatitis-during-acute-lymphoblastic-leukemia-therapy-a-case-report
#2
Anna Płotka, Agnieszka Wziątek, Jacek Wachowiak, Katarzyna Derwich
Acute pancreatitis in children acute lymphoblastic leukemia is commonly caused by drugs, for example, L-Asparaginase, pegapargase, steroids. The incidence of this complication is estimated at 6.7% to 18%. Although the majority of drug-induced acute pancreatitis cases are mild, severe cases can rarely occur. This work presents a case of successful management of a child with drug-induced necrotizing pancreatitis during acute lymphoblastic leukemia therapy. This case illustrates that comprehensive care and immediate intensive treatment can rescue patient despite poor prognosis...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29682773/mortality-data-from-the-european-adrenal-insufficiency-registry-patient-characterization-and-associations
#3
Marcus Quinkler, Bertil Ekman, Pinggao Zhang, Andrea M Isidori, Robert D Murray
OBJECTIVE: Mortality from primary and secondary adrenal insufficiency (AI; PAI and SAI, respectively) is 2-3-fold higher than in the general population. Mortality relates to cardiovascular disease, acute adrenal crisis (AC), cancer and infections; however, there has been little further characterization of patients who have died. DESIGN/METHODS: We analysed real-world data from 2034 patients (801 PAI, 1233 SAI) in the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387)...
April 22, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29682208/development-of-a-quantitative-pharmacodynamic-assay-for-apoptosis-in-fixed-tumor-tissue-and-its-application-in-distinguishing-cytotoxic-drug-induced-dna-double-strand-breaks-from-dna-double-strand-breaks-associated-with-apoptosis
#4
Angie B Dull, Deborah Wilsker, Melinda Hollingshead, Christina Mazcko, Christina M Annunziata, Amy K LeBlanc, James H Doroshow, Robert J Kinders, Ralph E Parchment
DNA double strand breaks (DSBs) induced by cancer therapeutic agents can lead to DNA damage repair or persistent DNA damage, which can induce apoptotic cell death; however, apoptosis also induces DSBs independent of genotoxic insult. γH2AX is an established biomarker for DSBs but cannot distinguish between these mechanisms. Activated cleaved caspase-3 (CC3) promotes apoptosis by enhancing nuclear condensation, DNA fragmentation, and plasma membrane blebbing. Here, we describe an immunofluorescence assay that distinguishes between apoptosis and drug-induced DSBs by measuring coexpression of γH2AX and membrane blebbing-associated CC3 to indicate apoptosis, and γH2AX in the absence of CC3 blebbing to indicate drug-induced DNA damage...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29681401/capacity-control-and-responsibility-in-parkinson-s-disease-patients-with-impulse-control-disorders-views-of-neurological-and-psychiatric-experts
#5
Andrew Dawson, Jordie Michael, Ella Dilkes-Frayne, Wayne Hall, Nadeeka N Dissanayaka, Adrian Carter
Dopamine replacement therapy can induce impulse control disorders (ICDs) (e.g., hypersexuality) in susceptible Parkinson's disease patients. ICDs can sometimes result in criminal offending. In a number of past Commonwealth cases, it appears offending ICD patients have been considered to be suffering from 'irresistible impulses' such that their decision-making capacity, behavioural control and responsibility were totally compromised. This contrasts with courts' general scepticism of drug-induced 'compulsion' in cases of addiction-related offending...
April 19, 2018: International Journal of Law and Psychiatry
https://www.readbyqxmd.com/read/29681192/in-vitro-assessment-of-cytotoxic-genotoxic-and-mutagenic-effects-of-antimalarial-drugs-artemisinin-and-artemether-in-human-lymphocytes
#6
Plínio Cerqueira Dos Santos Cardoso, Carlos Alberto Machado da Rocha, Tatiane Cristina Mota, Marcelo de Oliveira Bahia, Regianne Maciel Dos Santos Correa, Lorena Monteiro Gomes, Diego Di Felipe Avila Alcântara, Taíssa Maíra Thomaz Araújo, Leopoldo Silva de Moraes, Rommel Burbano
Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12...
April 22, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29679711/establishment-of-a-drug-induced-rhabdomyolysis-mouse-model-by-co-administration-of-ciprofloxacin-and-atorvastatin
#7
Akiko Matsubara, Shingo Oda, Sho Akai, Koichi Tsuneyama, Tsuyoshi Yokoi
Rhabdomyolysis is one of the serious side effects of ciprofloxacin (CPFX), a widely used antibacterial drug; and occasionally, acute kidney injury (AKI) occurs. Often, rhabdomyolysis has occurred in patients taking CPFX co-administered with statins. The purpose of this study is to establish a mouse model of drug-induced rhabdomyolysis by co-administration of CPFX and atorvastatin (ATV) and to clarify the mechanisms of its pathogenesis. C57BL/6J mice treated with L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor, were orally administered with CPFX and ATV for 4 days...
April 18, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29679557/acetaminophen-induced-liver-injury-is-attenuated-in-transgenic-fat-1-mice-endogenously-synthesizing-long-chain-n-3-fatty-acids
#8
Ruibing Feng, Yang Wang, Conghui Liu, Chunyan Yan, Hang Zhang, Huanxing Su, Jing X Kang, Chang-Zhen Shang, Jian-Bo Wan
Acetaminophen (APAP) overdose-caused hepatotoxicity is the most commonly cause of drugs-induced liver failurecharacterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29678448/detection-of-nanocarrier-potentiation-on-drug-induced-phospholipidosis-in-cultured-cells-and-primary-hepatocyte-spheroids-by-high-content-imaging-and-analysis
#9
Xihui Zhang, Liecheng Yang, Yongming Liu, Zhentao Song, Jian Zhao, Dandan Chen, Huan Yu, Ruibin Li, Yangyun Wang, Kai Yang, Yu Chen, Menghang Xia, Leshuai W Zhang
Considerable effort has been made to develop nanocarriers for controlled drug delivery over the last decade, while it remains unclear how the strength of adverse drug effect will be altered when a drug is loaded on the nanocarrier. Drug-induced phospholipidosis (DIP) is characterized with excessive accumulation of phospholipids in cells and is common for cationic amphiphilic drugs (CAD). Previously, we have reported that PEGylated graphene oxide (PEG-GO) loaded with several CAD can potentiate DIP. In current study, we extended our study on newly identified phospholipidosis (PLD) inducers that had been identified from the Library of Pharmacologically Active Compounds (LOPAC), to investigate if PEO-GO loaded with these CAD can alter DIP...
April 17, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29678162/tacrolimus-induced-parkinsonism-in-a-patient-after-liver-transplantation-case-report
#10
Karin Gmitterová, Michal Minár, Miroslav Žigrai, Zuzana Košutzká, Alice Kušnírová, Peter Valkovič
BACKGROUND: Hepatic encephalopathy may manifest by a wide spectrum of neuropsychiatric symptoms, including cognitive impairment, seizures or extrapyramidal symptoms. The liver transplant can lead to improvement of the signs of encephalopathy but subsequent immunosuppressive treatment might possess pronounced neurotoxicity. CASE PRESENTATION: We present a case report of a patient with chronic liver disease who developed signs of Parkinsonism after an orthotopic liver transplant, with consecutive immunosuppressant treatment with tacrolimus...
April 20, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#11
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29677409/is-there-an-association-between-heparin-induced-thrombocytopenia-hit-and-autoimmune-disease
#12
Brent Klinkhammer, Michael Gruchalla
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. PURPOSE: To provide clinical data to suggest an association between HIT and autoimmunity...
March 2018: WMJ: Official Publication of the State Medical Society of Wisconsin
https://www.readbyqxmd.com/read/29677086/hematologic-adverse-events-associated-with-prolonged-valganciclovir-treatment-in-congenital-cytomegalovirus-infection
#13
Liron Ziv, Joanne Yacobovich, Joseph Pardo, Havatzelet Yarden-Bilavsky, Jacob Amir, Micky Osovsky, Efraim Bilavsky
BACKGROUND: Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic congenital cytomegalovirus infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d. METHODS: A retrospective study. Infants with congenital cytomegalovirus treated with valganciclovir for 1 year were recruited...
April 19, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29676327/fluvoxamine-induced-intracranial-hypertension-in-a-10-year-old-boy
#14
Hemalini Samant, Preetam Samant
Drug-induced intracranial hypertension is a well-established entity. We report a rare case of intracranial hypertension with papilledema in a 10-year-old boy following use of fluvoxamine, a selective serotonin reuptake inhibitor. On discontinuing the drug, the papilledema resolved over 4 months without any residual visual anomalies. To the best of our knowledge, this is the first report of fluvoxamine-induced intracranial hypertension with papilledema.
May 2018: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29675997/hearing-vulnerability-after-noise-exposure-in-a-mouse-model-of-reactive-oxygen-species-overproduction
#15
Shigefumi Morioka, Hirofumi Sakaguchi, Taro Yamaguchi, Yuzuru Ninoyu, Hiroaki Mohri, Takashi Nakamura, Yasuo Hisa, Kiyokazu Ogita, Naoaki Saito, Takehiko Ueyama
Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29675458/bioengineered-liver-models-for-drug-testing-and-cell-differentiation-studies
#16
REVIEW
Gregory H Underhill, Salman R Khetani
In vitro models of the human liver are important for the following: (1) mitigating the risk of drug-induced liver injury to human beings, (2) modeling human liver diseases, (3) elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and (4) enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs), the gold standard for building human liver models, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrix-coated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29675322/reflective-lens-free-imaging-on-high-density-silicon-microelectrode-arrays-for-monitoring-and-evaluation-of-in-vitro-cardiac-contractility
#17
Thomas Pauwelyn, Richard Stahl, Lakyn Mayo, Xuan Zheng, Andy Lambrechts, Stefan Janssens, Liesbet Lagae, Veerle Reumers, Dries Braeken
The high rate of drug attrition caused by cardiotoxicity is a major challenge for drug development. Here, we developed a reflective lens-free imaging (RLFI) approach to non-invasively record in vitro cell deformation in cardiac monolayers with high temporal (169 fps) and non-reconstructed spatial resolution (352 µm) over a field-of-view of maximally 57 mm2 . The method is compatible with opaque surfaces and silicon-based devices. Further, we demonstrated that the system can detect the impairment of both contractility and fast excitation waves in cardiac monolayers...
April 1, 2018: Biomedical Optics Express
https://www.readbyqxmd.com/read/29673198/chemoresistance-to-cancer-treatment-benzo-%C3%AE-pyrene-as-friend-or-foe
#18
Kevin Dzobo, Naseeha Hassen, Dimakatso Alice Senthebane, Nicholas Ekow Thomford, Arielle Rowe, Hendrina Shipanga, Ambroise Wonkam, M Iqbal Parker, Shaheen Mowla, Collet Dandara
Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel...
April 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29672845/drug-induced-proarrhythmia-and-torsade-de-pointes-a-primer-for-students-and-practitioners-of-medicine-and-pharmacy
#19
REVIEW
J Rick Turner, Ignacio Rodriguez, Emily Mantovani, Gary Gintant, Peter R Kowey, Ralph J Klotzbaugh, Krishna Prasad, Philip T Sager, Norman Stockbridge, Colette Strnadova
Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability...
April 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29671953/bone-marrow-as-a-target-organ-of-systemic-lupus-erythematosus-analysis-of-cases-with-myelofibrosis
#20
Döndü Üsküdar Cansu, Hava Üsküdar Teke, Serap Işiksoy, Cengiz Korkmaz
AIM: Cytopenia in the course of systemic lupus erythematosus (SLE) may be due to multiple factors. In this study, we aimed primarily to evaluate the detailed results of bone marrow (BM) biopsies of SLE patients, secondly to determine the myelofibrosis (MF) frequency and thirdly to compare BM morphologic findings as well as the clinical and laboratory parameters between groups (with MF and without MF) in cytopenic SLE patients. METHODS: We retrospectively analyzed 224 SLE patients' files...
April 19, 2018: International Journal of Rheumatic Diseases
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