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https://www.readbyqxmd.com/read/29161763/quantifying-the-relationship-between-inhibition-of-vegfr-2-drug-induced-blood-pressure-elevation-and-hypertension
#1
Teresa Collins, Kelly Gray, Michal Bista, Matt Skinner, Christopher Hardy, Haiyun Wang, Jerome T Mettetal, Alexander R Harmer
BACKGROUND AND PURPOSE: Several anti-angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15-60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off-target activity at VEGFR-2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR-2 off-target potency into blood pressure elevation would be useful in development of novel TKIs. EXPERIMENTAL APPROACH: We sought to quantify the relationship between VEGFR-2 inhibition and blood pressure elevation for a range of kinase inhibitors...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29160385/usual-interstitial-pneumonia-typical-possible-and-inconsistent-patterns
#2
Pedro Paulo Teixeira E Silva Torres, Marcelo Fouad Rabahi, Maria Auxiliadora Carmo Moreira, Gustavo de Souza Portes Meirelles, Edson Marchiori
Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated "possible UIP"; and a pattern designated "inconsistent with UIP", each pattern having important diagnostic implications...
September 2017: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
https://www.readbyqxmd.com/read/29159025/comparison-of-the-inhibition-potentials-of-icotinib-and-erlotinib-against-human-udp-glucuronosyltransferase-1a1
#3
Xuewei Cheng, Xia Lv, Hengyan Qu, Dandan Li, Mengmeng Hu, Wenzhi Guo, Guangbo Ge, Ruihua Dong
UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29158822/liposomal-64-cu-pet-imaging-of-anti-vegf-drug-effects-on-liposomal-delivery-to-colon-cancer-xenografts
#4
Stephanie J Blocker, Kirk A Douglas, Lisa Anne Polin, Helen Lee, Bart S Hendriks, Enxhi Lalo, Wei Chen, Anthony F Shields
Liposomes (LP) deliver drug to tumors due to enhanced permeability and retention (EPR). LP were labeled with (64)Cu for positron emission tomography (PET) to image tumor localization. Bevacizumab (bev), a VEGF targeted antibody, may modify LP delivery by altering tumor EPR and this change can also be imaged. Objective: Assess the utility of (64)Cu-labeled LP for PET in measuring altered LP delivery early after treatment with bev. Methods: HT-29 human colorectal adenocarcinoma tumors were grown subcutaneously in SCID mice...
2017: Theranostics
https://www.readbyqxmd.com/read/29157021/gastroparesis-pharmacotherapy-and-cardiac-risk
#5
Per M Hellström, Ahmad Al-Saffar
BACKGROUND: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs. OBJECTIVE: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics...
November 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29156531/heated-naringin-mitigate-the-genotoxicity-effect-of-mitomycin-c-in-balb-c-mice-through-enhancing-the-antioxidant-status
#6
Mouna Maatouk, Nadia Mustapha, Imen Mokdad-Bzeouich, Hind Chaaban, Irina Ioannou, Kamel Ghedira, Mohamed Ghoul, Leila Chekir-Ghedira
A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156406/target-catalyzed-hairpin-assembly-and-metal-organic-frameworks-mediated-nonenzymatic-co-reaction-for-multiple-signal-amplification-detection-of-mir-122-in-human-serum
#7
Yuliang Li, Chao Yu, Bo Yang, Zhirui Liu, Peiyuan Xia, Qian Wang
Herein, a new type of multifunctional iron based metal-organic frameworks (PdNPs@Fe-MOFs) has been synthesized by assembly palladium nanoparticles on the surface of Fe-MIL-88NH2 MOFs microcrystals, and first applied in electrochemical biosensor for ultrasensitive detection of microRNA-122 (miR-122, a biomarker of drug-induced liver injury). The nanohybrids have not only been utilized as ideal nanocarriers for immobilization of signal probes, but also used as redox probes and electrocatalysts. In this biosensor, two hairpin probes were designed as capture probes and signal probes, respectively...
November 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29155772/preparation-of-primary-acute-lymphoblastic-leukemia-cells-in-different-cell-cycle-phases-by-centrifugal-elutriation
#8
Magdalena Delgado, Anisha Kothari, Walter N Hittelman, Timothy C Chambers
The ability to synchronize cells has been central to advancing our understanding of cell cycle regulation. Common techniques employed include serum deprivation; chemicals which arrest cells at different cell cycle phases; or the use of mitotic shake-off which exploits their reduced adherence. However, all of these have disadvantages. For example, serum starvation works well for normal cells but less well for tumor cells with compromised cell cycle checkpoints due to oncogene activation or tumor suppressor loss...
November 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155539/sore-or-swollen-lips-part-2-systemic-causes
#9
Dimitrios Malamos, Crispian Scully
This series of three papers reviews the causes, diagnosis and differential diagnosis, and outlines the management of sore and/or swollen lips. Clinical relevance: Sore and/or swollen lips are not uncommon, often have a local cause, but may reflect a systemic disease. The previous article reviewed important causes, from actinic to contact cheilitis, while this paper starts with drug-induced cheilitis and completes that alphabetical list.
December 2016: Dental Update
https://www.readbyqxmd.com/read/29155283/comparative-analysis-of-media-effects-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-in-proarrhythmia-risk-assessment
#10
Derek Schocken, Jayna Stohlman, Jose Vicente, Dulciana Chan, Dakshesh Patel, Murali Krishna Matta, Vikram Patel, Mathew Brock, Daniel Millard, James Ross, David G Strauss, Ksenia Blinova
INTRODUCTION: Cardiotoxicity assessment using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) forms a key component of the Comprehensive in Vitro Proarrhythmia Assay (CiPA). A potentially impactful factor on iPSC-CM testing is the presence of serum in the experimental media. Generally, serum-free media is used to most accurately reproduce "free" drug concentration. However, caution is needed; drug solubility and cardiomyocyte electrophysiology could be affected by media formulation, potentially impacting interpretation of drug-induced effects...
November 16, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29154756/cocaine-induced-adaptation-of-dopamine-d2s-but-not-d2l-autoreceptors
#11
Brooks G Robinson, Alec F Condon, Daniela Radl, Emiliana Borrelli, John T Williams, Kim A Neve
The dopamine D2 receptor has two splice variants, D2S (Short) and D2L (Long). In dopamine neurons, both variants can act as autoreceptors to regulate neuronal excitability and dopamine release, but the roles of each variant are incompletely characterized. In a previous study we used viral receptor expression in D2 receptor knockout mice to show distinct effects of calcium signaling on D2S and D2L autoreceptor function (Gantz et al., 2015). However, the cocaine-induced plasticity of D2 receptor desensitization observed in wild type mice was not recapitulated with this method of receptor expression...
November 20, 2017: ELife
https://www.readbyqxmd.com/read/29154364/non-contingent-exposure-to-amphetamine-in-adolescence-recruits-mir-218-to-regulate-dcc-expression-in-the-vta
#12
Santiago Cuesta, José Maria Restrepo-Lozano, Steven Silvestrin, Dominique Nouel, Angélica Torres-Berrio, Lauren M Reynolds, Andreas Arvanitogiannis, Cecilia Flores
The development of the dopamine input to the medial prefrontal cortex occurs during adolescence and is a process that is vulnerable to disruption by stimulant drugs such as amphetamine. We have previously linked the amphetamine-induced disruption of dopamine connectivity and prefrontal cortex maturation during adolescence to the downregulation of the Netrin-1 receptor, DCC, in dopamine neurons. However, how DCC expression in dopamine neurons is itself regulated is completely unknown. MicroRNA (miRNA) regulation of mRNA translation and stability is a prominent mechanism linking environmental events to changes in protein expression...
November 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29154132/dexmedetomidine-promotes-biomimetic-non-rapid-eye-movement-stage-3-sleep-in-humans-a-pilot-study
#13
Oluwaseun Akeju, Lauren E Hobbs, Lei Gao, Sara M Burns, Kara J Pavone, George S Plummer, Elisa C Walsh, Tim T Houle, Seong-Eun Kim, Matt T Bianchi, Jeffrey M Ellenbogen, Emery N Brown
OBJECTIVES: Sleep, which comprises of rapid eye movement (REM) and non-REM stages 1-3 (N1-N3), is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function. The principal sedative drugs produce electroencephalogram beta oscillations, which have been associated with neurocognitive dysfunction. Pharmacological induction of altered arousal states that neurophysiologically approximate natural sleep, termed biomimetic sleep, may eliminate drug-induced neurocognitive dysfunction...
October 20, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29152493/a-pilot-study-evaluating-biomarker-development-for-drug-induced-chronic-eczematous-eruptions-of-aging-individuals
#14
Erika Mae Summers, Nicholas Ray Blickenstaff, Garrett Curtis Coman, Thomas Bernd Martins, Harry Raymond Hill, Richard Dennis Sontheimer
Background: Identifying the drug(s) responsible for drug-induced chronic eczematous eruptions of aging individuals (CEEA) is a clinical challenge in patients on multiple medications. Reliable in vitro testing methods and biomarkers are needed to identify the causative agent and allow simultaneous assessment of T-cell responses to multiple drugs being taken concurrently. This study examined the feasibility of using in vitro, drug-specific T cell activation responses as a biomarker for drug-induced CEEA...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29152127/minocycline-treatment-increases-resistance-to-oxidative-stress-and-extends-lifespan-in-drosophila-via-foxo
#15
Gang Jun Lee, Jin Ju Lim, Seogang Hyun
Minocycline is a semi-synthetic tetracycline derivative antibiotic that has received increasing attention for its non-antibiotic properties, mainly anti-inflammatory, tumor-suppressive, and neuroprotective effects. Drosophila is a widely used genetically tractable model organism for studying organismal aging by virtue of its short lifespan and ease of cultivation. In this study, we examined the effects of minocycline on Drosophila lifespan and its associated traits. Minocycline-supplemented food significantly extended lifespan in both Canton S and w(1118) Drosophila strains...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152060/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#16
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152040/ayurvedic-drug-induced-liver-injury
#17
Kunal K Dalal, Thomas Holdbrook, Steven R Peikin
Drug induced liver injury is responsible for 50% of acute liver failure in developed countries. Ayurvedic and homeopathic medicine have been linked to liver injury. This case describes the first documented case of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. Drug induced liver injury may be difficult to diagnosis, but use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging, is recommended. Advanced imaging, such as magnetic resonance cholangiopancreatography, may possibly have a greater role than previously reported in literature...
November 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/29150609/atomic-resolution-snapshot-of-leishmania-ribosome-inhibition-by-the-aminoglycoside-paromomycin
#18
Moran Shalev-Benami, Yan Zhang, Haim Rozenberg, Yuko Nobe, Masato Taoka, Donna Matzov, Ella Zimmerman, Anat Bashan, Toshiaki Isobe, Charles L Jaffe, Ada Yonath, Georgios Skiniotis
Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149926/drug-induced-gastrointestinal-and-hepatic-disease-associated-with-biologics-and-nonbiologic-disease-modifying-antirheumatic-drugs
#19
REVIEW
Patrick R Wood, Liron Caplan
A variety of gastrointestinal adverse drug reactions are seen in nearly all conventional antirheumatic medications, ranging from nausea to life-threatening drug-induced liver injury. Rheumatologists should be particularly familiar with hepatotoxicity associated with long-term methotrexate use, and the range of unique hepatic, biliary, and pancreatic manifestations associated with azathioprine. Hepatitis B virus reactivation is the most serious gastrointestinal disease risk associated with many biological therapies, particularly rituximab...
February 2018: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/29148292/cholestatic-liver-injury-as-a-side-effect-of-dabigatran-and-the-use-of-coagulation-tests-in-dabigatran-intoxication-and-after-reversal-by-idarucizumab-in-bleeding-and-sepsis
#20
Willemijn J Comuth, Anne-Mette Haase, Linda Ø Henriksen, Jerzy Malczynski, Daan van de Kerkhof, Anna-Marie B Münster
Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure...
November 17, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
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