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https://www.readbyqxmd.com/read/28719724/synthesis-and-properties-of-new-n-heteroheptacenes-for-solution-based-organic-field-effect-transistors
#1
Fei Zhou, Sheng Liu, Bernard D Santarsiero, Donald J Wink, Damien Boudinet, Antonio Facchetti, Tom G Driver
A series of N-heteroheptacenes was synthesized from ortho-thiophene-substituted aryl azides using a Rh2(II)-catalyzed C-H bond amination reaction to construct the thienoindole moieties. This reaction tolerated the presence of electron-donating or withdrawing groups on the aryl azide without adversely affecting the yield of the amination reaction. The central thiophene ring was created from two thienoindole pieces through a Pd-catalyzed Stille reaction to install the thioether followed by a Cu-mediated Ullman reaction to trigger the cyclization...
July 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#2
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#3
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718506/felbamate-as-an-add-on-therapy-for-refractory-partial-epilepsy
#4
REVIEW
Li Li Shi, JianCheng Dong, HengJian Ni, JinSong Geng, Taixiang Wu
BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2014) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and we have assessed its effects as an add-on therapy to standard drugs in this review...
July 18, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#5
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717823/-interdisciplinary-pain-assessment-in-the-hospital-setting-merely-a%C3%A2-door-opener-to-multimodal-pain-therapy
#6
E Sens, M Mothes-Lasch, J F Lutz
BACKGROUND: Chronic pain is characterized by a complex interaction of somatic, mental and social factors. Assessing these factors in patients with chronic pain is vital during the diagnostic work-up and when making a structured treatment plan. Interdisciplinary pain assessment (ISA) is the most promising method to deal with these challenges. This article presents our experience in performing pain assessments in the hospital setting and also illustrates the characteristic features of chronic pain patients undergoing such assessments...
July 17, 2017: Der Schmerz
https://www.readbyqxmd.com/read/28717101/mechanism-based-risk-assessment-strategy-for-drug-induced-cholestasis-using-the-transcriptional-benchmark-dose-derived-by-toxicogenomics
#7
Taisuke Kawamoto, Yuichi Ito, Osamu Morita, Hiroshi Honda
Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717052/withdrawal-of-tracheostomy-ventilation-in-motor-neurone-disease-implementing-advance-directives
#8
EDITORIAL
Christopher J McDermott, Christina Faull
No abstract text is available yet for this article.
July 17, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28716996/long-term-benzodiazepine-and-z-drugs-use-in-the-uk-a-survey-of-general-practice
#9
James Davies, Todd C Rae, Luke Montagu
BACKGROUND: Current British National Formulary (BNF) guidelines state that benzodiazepines and zolpidem, zopiclone, and zaleplon, commonly known as Z-drugs (BZD), be prescribed for no more than 4 weeks, although anecdotal data suggest that many patients are prescribed BZDs for much longer. As there are no recent, evidence-based estimates of long-term (>12 months) BZD use in the UK, the scale of this potential problem is unknown. AIM: To produce the first reliable, evidence-based estimate of long-term BZD use in the UK...
July 17, 2017: British Journal of General Practice: the Journal of the Royal College of General Practitioners
https://www.readbyqxmd.com/read/28716953/a-novel-in-vitro-analog-expressing-learning-induced-cellular-correlates-in-distinct-neural-circuits
#10
Harris A Weisz, Marcy L Wainwright, Riccardo Mozzachiodi
When presented with noxious stimuli, Aplysia exhibits concurrent sensitization of defensive responses, such as the tail-induced siphon withdrawal reflex (TSWR) and suppression of feeding. At the cellular level, sensitization of the TSWR is accompanied by an increase in the excitability of the tail sensory neurons (TSNs) that elicit the reflex, whereas feeding suppression is accompanied by decreased excitability of B51, a decision-making neuron in the feeding neural circuit. The goal of this study was to develop an in vitro analog coexpressing the above cellular correlates...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28716819/effect-of-type-2-diabetes-surgical-incision-and-volatile-anesthesia-on-hemodynamics-in-the-rat
#11
Carol T Bussey, Regis R Lamberts
Diabetic patients have increased cardiac complications during surgery, possibly due to impaired autonomic regulation. Anesthesia lowers blood pressure and heart rate (HR), whereas surgical intervention has opposing effects. The interaction of anesthesia and surgical intervention on hemodynamics in diabetes is unknown, despite being a potential perioperative risk factor. We aimed to determine the effect of diabetes on the integrative interaction between hemodynamics, anesthesia, and surgical incision. Zucker type 2 diabetic rats (DM) and their nondiabetic littermates (ND) were implanted with an intravenous port for drug delivery, and a radiotelemeter to measure mean arterial blood pressure (MAP) and derive HR (total n = 50)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28716675/what-we-imagine-is-what-we-do-a-critical-overview-about-mental-imagery-as-a-strategy-to-study-human-defensive-responses
#12
REVIEW
Rosana Shuhama, D Caroline Blanchard, Frederico Guilherme Graeff, Cristina Marta Del-Ben
There is not a single and perfect instinctive behavior to react to threatening situations. However, the study of particular features of these situations suggests the existence of prototypical emotional reactions and associated defensive behaviors. Since all living beings are subjected to common evolutionary pressures, such as predation and conspecific competition, it is plausible that there is conservation of some basic defensive responses in their behavioral repertoire. The choice for approaching or withdrawing from a given situation depends, among others things, on environmental features, including the threat intensity and the distance from the source of the threat...
July 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28716639/design-synthesis-and-biological-evaluation-of-novel-4-phenoxyquinoline-derivatives-containing-3-oxo-3-4-dihydroquinoxaline-moiety-as-c-met-kinase-inhibitors
#13
Ju Liu, Di Yang, Xiuxiu Yang, Minhua Nie, Guodong Wu, Zhunchao Wang, Wei Li, Yajing Liu, Ping Gong
A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0...
June 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28716269/dopamine-agonist-withdrawal-syndrome-daws-in-a-tertiary-parkinson-disease-treatment-center
#14
Shnehal Patel, Xiomara Garcia, Mohammad Edrees Mohammad, Xin Xin Yu, Katelyn Vlastaris, Kaley O'Donnell, Kathryn Sutton, Hubert H Fernandez
INTRODUCTION: Dopamine agonists are a mainstay of treatment for patients with Parkinson disease (PD). However, side effects limit their use, often necessitating dose change. Upon withdrawal, patients may experience dopamine agonist withdrawal syndrome (DAWS). To date, there is no established protocol for the prevention or treatment of DAWS. METHODS: We performed a retrospective chart review of PD patients who were taking a dopamine agonist. RESULTS: In our large cohort of 313 PD patients who were on a dopamine agonist, we found that 39...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28716221/parkin-mutation-may-be-associated-with-serious-akinesia-in-a-patient-with-parkinson-s-disease
#15
Yuto Uchihara, Hiroshi Kataoka, Hiroyo Yoshino, Ryogo Syobatake, Nobutaka Hattori, Satoshi Ueno
Acute akinesia (AA) is an unusual motor complication in Parkinson's disease (PD). Reported risk factors for AA include infection, trauma, surgical intervention, and the withdrawal of antiparkinsonian medication. Recently, patients with genetic PD were reported to have a three-fold risk of AA than patients with non-genetic PD. We describe a patient with PD associated with a Parkin mutation in whom serious akinesia developed. A 42-year-old man with exon 2 heterozygous deletion and exon 4 heterozygous deletion in the PARK2 gene showed five unexpected AA for several 12h...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715848/patient-outcomes-in-dose-reduction-or-discontinuation-of-long-term-opioid-therapy-a-systematic-review
#16
Joseph W Frank, Travis I Lovejoy, William C Becker, Benjamin J Morasco, Christopher J Koenig, Lilian Hoffecker, Hannah R Dischinger, Steven K Dobscha, Erin E Krebs
Background: Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. Purpose: To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. Data Sources: MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts...
July 18, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28715126/an-engineered-photoswitchable-mammalian-pyruvate-kinase
#17
Stefanie Gehrig, Jamie A Macpherson, Paul C Driscoll, Alastair Symon, Stephen R Martin, James I MacRae, Jens Kleinjung, Franca Fraternali, Dimitrios Anastasiou
Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28714785/effects-of-alcohol-on-inhibitory-avoidance-learning-in-zebrafish-danio-rerio
#18
Ricardo Rodrigues Amorim, Priscila Fernandes Silva, Ana Carolina Luchiari
The zebrafish (Danio rerio) can be used in studies addressing the effects of drugs on learning, memory, and anxiety. In the present study, we investigated the effect of different alcohol treatments (chronic and acute) on the learning and anxiety response of zebrafish in an inhibitory avoidance paradigm. Zebrafish were initially exposed to different alcohol treatments and submitted to an inhibitory avoidance protocol, where an electroshock was applied to the fish as they swam from the white to the black side of a shuttle box tank (naturally preferred environment of zebrafish)...
July 17, 2017: Zebrafish
https://www.readbyqxmd.com/read/28714716/cb%C3%A2-receptor-antagonism-in-the-bed-nucleus-of-the-stria-terminalis-interferes-with-affective-opioid-withdrawal-in-rats
#19
Kiri L Wills, Marieka V DeVuono, Cheryl L Limebeer, Kiran Vemuri, Alexandros Makriyannis, Linda A Parker
The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region. Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28714604/antidepressants-antipsychotics-and-mood-stabilizers-in-pregnancy-what-do-we-know-and-how-should-we-treat-pregnant-women-with-depression
#20
REVIEW
Asher Ornoy, Liza Weinstein-Fudim, Zivanit Ergaz
Depression is generally treated with antidepressants, but may often need antipsychotics and mood stabilizers. We discuss the updated data regarding the safety in pregnancy of antidepressants and antipsychotics, except selective serotonin reuptake inhibitors, and their possible impact on the long-term development of the offspring. Several earlier studies demonstrated a slight increase in the rate of major anomalies following maternal tricyclic antidepressant treatment, but most current literature shows their relative safety in pregnancy...
July 17, 2017: Birth defects research
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