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https://www.readbyqxmd.com/read/29242534/the-celecoxib-derivatives-ar-12-and-ar-14-induce-autophagy-and-clear-prion-infected-cells-from-prions
#1
Basant A Abdulrahman, Dalia Abdelaziz, Simrika Thapa, Li Lu, Shubha Jain, Sabine Gilch, Stefan Proniuk, Alexander Zukiwski, Hermann M Schatzl
Prion diseases are fatal infectious neurodegenerative disorders that affect both humans and animals. The autocatalytic conversion of the cellular prion protein (PrPC) into the pathologic isoform PrPSc is a key feature in prion pathogenesis. AR-12 is an IND-approved derivative of celecoxib that demonstrated preclinical activity against several microbial diseases. Recently, AR-12 has been shown to facilitate clearance of misfolded proteins. The latter proposes AR-12 to be a potential therapeutic agent for neurodegenerative disorders...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29237937/drug-induced-liver-injury-due-to-lepidium-meyenii-maca-medicinal-liquor
#2
An Xiao, Hai-Ying He, Qing Chen, Shi-Wu Ma
No abstract text is available yet for this article.
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29237052/multimode-drug-inducible-crispr-cas9-devices-for-transcriptional-activation-and-genome-editing
#3
Jia Lu, Chen Zhao, Yingze Zhao, Jingfang Zhang, Yue Zhang, Li Chen, Qiyuan Han, Yue Ying, Shuai Peng, Runna Ai, Yu Wang
Precise investigation and manipulation of dynamic biological processes often requires molecular modulation in a controlled inducible manner. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) has emerged as a versatile tool for targeted gene editing and transcriptional programming. Here, we designed and vigorously optimized a series of Hybrid drug Inducible CRISPR/Cas9 Technologies (HIT) for transcriptional activation by grafting a mutated human estrogen receptor (ERT2) to multiple CRISPR/Cas9 systems, which renders them 4-hydroxytamoxifen (4-OHT) inducible for the access of genome...
December 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29235465/molecular-basis-of-differential-3-splice-site-sensitivity-to-anti-tumor-drugs-targeting-u2-snrnp
#4
Luisa Vigevani, André Gohr, Thomas Webb, Manuel Irimia, Juan Valcárcel
Several splicing-modulating compounds, including Sudemycins and Spliceostatin A, display anti-tumor properties. Combining transcriptome, bioinformatic and mutagenesis analyses, we delineate sequence determinants of the differential sensitivity of 3' splice sites to these drugs. Sequences 5' from the branch point (BP) region strongly influence drug sensitivity, with additional functional BPs reducing, and BP-like sequences allowing, drug responses. Drug-induced retained introns are typically shorter, displaying higher GC content and weaker polypyrimidine-tracts and BPs...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29235453/potential-impact-of-thermal-effects-during-ultrasonic-neurostimulation-retrospective-numerical-estimation-of-temperature-elevation-in-seven-rodent-setups
#5
Charlotte Constans, Philippe Mateo, Mickael Tanter, Jean-Francois Aubry
In the past decade, a handful but growing number of groups have reported worldwide successful low intensity focused ultrasound induced neurostimulation trials on rodents with effects ranging from movement elicitations to reduction of anesthesia time or reduction of the duration of drug induced seizures. The mechanisms underlying ultrasonic neuromodulation are still not fully understood. Given the low intensities used in most of the studies, a mechanical effect is more likely to be responsible for the neuromodulation effect, but a clear description of the thermal and mechanical effects is necessary to optimize clinical applications...
December 13, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29235390/mir-122-and-other-micrornas-as-potential-circulating-biomarkers-of-drug-induced-liver-injury
#6
Lawrence S Howell, Lucy Ireland, B Kevin Park, Christopher E Goldring
Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits pre-clinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers. Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI...
December 13, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29234678/follow-up-measurement-of-corrected-qt-interval-in-adult-patients-before-and-after-lung-transplantation
#7
Dirk Bandorski, Reinhard Hoeltgen, Nicole Becker, Winfried Padberg, Harilaos Bogossian, Christoph Wiedenroth, Matthias Arlt, Christian Hamm, Werner Seeger, Hossein Ardeschir Ghofrani, Matthias Hecker, Henning Gall, Konstantin Mayer
Background: Prolongation of the corrected QT (QTc) interval is well known for many drugs, some of which are an integral part of the therapeutic regimen after lung transplantation (LTX). Therefore, we investigated the QTc interval after LTX in the present study. Patients and Methods: The medical records of patients after LTX were studied for demographic data, indication of LTX, medication, and baseline and follow-up ECGs. The QT interval was corrected for the patient's heart rate using the different formulae of Bazett, Fridericia, Hodges, and Framingham...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29233316/pharmacy-residents-as-primary-educators-within-a-professional-pharmacy-elective
#8
Meredith L Howard, Taylor D Steuber, Alison M Walton, Sarah A Nisly
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the impact of a course change from a faculty-led professional pharmacy elective to a primarily pharmacy resident-led course on student satisfaction and learning. EDUCATIONAL ACTIVITY AND SETTING: In 2014, pharmacy residents were transitioned into primary teaching roles in a drug-induced diseases elective to increase student exposure to residents and different teaching styles. Student learning roles did not change...
September 2017: Currents in Pharmacy Teaching & Learning
https://www.readbyqxmd.com/read/29232800/-a-case-of-fulminant-hepatitis-after-administration-of-abiraterone-acetate
#9
Satoru Yumiba, Kazuhiko Komori, Toshichika Iwanishi, Youhei Koida, Masao Kobayashi, Yutaka Ono
A 77-year-old man with castration-resistant prostate cancer (CRPC) received abiraterone acetate in October 2014. He visited our outpatient clinic because of general malaise and anorexia 27 days after starting abiraterone acetate. The lab test showed hepatic dysfunction (aspartate transaminase, AST 440 U/l, alanine transaminase, ALT 420 U/l) and the elevation of liver enzymes continued on the next day even after stopping abiraterone acetate. Three days later, he was hospitalized due to severe elevation of liver enzymes (AST 1,171 U/l, ALT 1,487 U/l) , and the decreased prothrombin activity (60...
November 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/29232689/a-computational-model-for-regulation-of-nanoscale-glucan-exposure-in-candida-albicans
#10
Michael J Wester, Jia Lin, Aaron K Neumann
Candida albicans is a virulent human opportunistic pathogen. It evades innate immune surveillance by masking an immunogenic cell wall polysaccharide, β-glucan, from recognition by the immunoreceptor Dectin-1. Glucan unmasking by the antifungal drug caspofungin leads to changes in the nanostructure of glucan exposure accessible to Dectin-1. The physical mechanism that regulates glucan exposure is poorly understood, but it controls the nanobiology of fungal pathogen recognition. We created computational models to simulate hypothetical physical processes of unmasking glucan in a biologically realistic distribution of cell wall glucan fibrils...
2017: PloS One
https://www.readbyqxmd.com/read/29230302/letrozole-induced-hepatitis-with-autoimmune-features-a-rare-adverse-drug-reaction-with-review-of-the-relevant-literature
#11
Bharatsinh Gharia, Karan Seegobin, Satish Maharaj, Noor Marji, Amie Deutch, Lara Zuberi
While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis...
November 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29229971/development-of-decision-forest-models-for-prediction-of-drug-induced-liver-injury-in-humans-using-a-large-set-of-fda-approved-drugs
#12
Huixiao Hong, Shraddha Thakkar, Minjun Chen, Weida Tong
Drug-induced liver injury (DILI) presents a significant challenge to drug development and regulatory science. The FDA's Liver Toxicity Knowledge Base (LTKB) evaluated >1000 drugs for their likelihood of causing DILI in humans, of which >700 drugs were classified into three categories (most-DILI, less-DILI, and no-DILI). Based on this dataset, we developed and compared 2-class and 3-class DILI prediction models using the machine learning algorithm of Decision Forest (DF) with Mold2 structural descriptors...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229868/sex-dependent-differences-in-inflammatory-responses-during-liver-regeneration-in-a-murine-model-of-acute-liver-injury
#13
Debora Bizzaro, Marika Crescenzi, Rosa Di Liddo, Diletta Arcidiacono, Andrea Cappon, Thomas Bertalot, Vincenzo Amodio, Alessia Tasso, Annalisa Stefani, Valentina Bertazzo, Giacomo Germani, Chiara Frasson, Giuseppe Basso, Pierpaolo Parnigotto, Malcolm Ronald Alison, Patrizia Burra, Maria Teresa Conconi, Francesco Paolo Russo
A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and sacrificed after 3, 5 and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide...
December 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29229836/single-cell-analysis-resolves-the-cell-state-transition-and-signaling-dynamics-associated-with-melanoma-drug-induced-resistance
#14
Yapeng Su, Wei Wei, Lidia Robert, Min Xue, Jennifer Tsoi, Angel Garcia-Diaz, Blanca Homet Moreno, Jungwoo Kim, Rachel H Ng, Jihoon W Lee, Richard C Koya, Begonya Comin-Anduix, Thomas G Graeber, Antoni Ribas, James R Heath
Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAFV600 -mutant melanoma cell lines. A subset of plastic cell lines, which followed a trajectory covering multiple known cell state transitions, provided models for more detailed biophysical investigations...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229311/an-extra-priming-dose-of-hepatitis-a-vaccine-to-adult-patients-with-rheumatoid-arthritis-and-drug-induced-immunosuppression-a-prospective-open-label-multi-center-study
#15
Anja Rosdahl, Christian Herzog, Gert Frösner, Torbjörn Norén, Lars Rombo, Helena H Askling
BACKGROUND: Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion. METHOD: Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months...
December 8, 2017: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/29226716/-case-report-on-choroidal-effusion-after-oral-acetazolamide-administration-an-unusual-manifestation-of-a-well-known-idiosyncratic-effect
#16
András Hári-Kovács, Judit Soós, Tamás Gyetvai, Andrea Facskó, Mihály Végh
Sulpha drugs are widely employed in medicine for various diseases and disorders. During the last several decades, numerous papers had been published on supra ciliary and posterior choroidal effusion likely presenting as an idiosyncratic effect of these drugs especially of acetazolamide. In each publication, the effusion was associated with either an acute angle-closure glaucoma or transitory myopia or both of these as leading symptoms. In the current publication, authors report on two cases where the acetazolamide-induced choroidal effusion was an accidental finding without either a myopic shift in refraction or an acute elevation in intraocular pressure...
December 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29226391/experience-with-leflunomide-as-treatment-and-as-secondary-prophylaxis-for-cytomegalovirus-infection-in-lung-transplant-recipients-a-case-series-and-review-of-the-literature
#17
Jose Tiago Silva, Virginia Pérez-González, Francisco López-Medrano, Rodrigo Alonso-Moralejo, Mario Fernández-Ruiz, Rafael San-Juan, Patricia Brañas, María Dolores Folgueira, José María Aguado, Alicia de Pablo-Gafas
Data concerning the use of leflunomide -a drug approved for rheumatoid arthritis with in vitro anti-cytomegalovirus (CMV) activity- in lung transplant (LT) recipients are scarce. We performed a single center retrospective study including LT recipients who received leflunomide for CMV infection or as secondary prophylaxis after viremia clearance. We also conducted a full systematic PubMed search until June 30, 2017. We identified 5 LT recipients in our center, plus 7 patients reported in the literature. All patients had previously received ganciclovir (GCV) and foscarnet, with drug-induced adverse effects described in 6 recipients (50%)...
December 11, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29226159/immunohistopathological-findings-of-severe-cutaneous-adverse-drug-reactions
#18
REVIEW
Mari Orime
Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29225987/daptomycin-induced-acute-eosinophilic-pneumonia-late-onset-and-quick-recovery
#19
Mohamad Rachid, Khansa Ahmad, Meghan Saunders-Kurban, Aelia Fatima, Aditya Shah, Anas Nahhas
Background: Daptomycin is a cyclic lipopeptide antibiotic that provides great coverage for gram positive cocci. From the early years of daptomycin use, concerns were raised regarding the pulmonary side effects of daptomycin and potential development of acute eosinophilic pneumonia (AEP) secondary to daptomycin therapy. Discussion: AEP could be idiopathic or induced by drugs or toxins. It is a distinct entity from atopic diseases and autoimmune, parasitic, or fungal infections that can also cause pulmonary eosinophilia...
2017: Case Reports in Pulmonology
https://www.readbyqxmd.com/read/29225856/severe-piperacillin-tazobactam-induced-hemolysis-in-a-cystic-fibrosis-patient
#20
Andrew D Kerkhoff, Lauren Patrick, Patricia Cornett, Mary-Ellen Kleinhenz, Sam Brondfield
Piperacillin-tazobactam is one of the most common causes of drug-induced immune hemolytic anemia (DIIHA) and is frequently utilized, especially in patients with cystic fibrosis (CF). Here, we report a case of life-threatening piperacillin-tazobactam-associated DIIHA in a 30-year-old woman with CF and propose management recommendations for piperacillin-tazobactam-associated DIIHA in CF patients.
December 2017: Clinical Case Reports
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