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https://www.readbyqxmd.com/read/30310471/assessing-the-haemodynamic-impact-of-coronary-artery-stenoses-intracoronary-flow-versus-pressure-measurements
#1
REVIEW
Valérie E Stegehuis, Gilbert Wm Wijntjens, Tadashi Murai, Jan J Piek, Tim P van de Hoef
Fractional flow reserve (FFR)-guided percutaneous coronary intervention results in better long-term clinical outcomes compared with coronary angiography alone in intermediate stenoses in stable coronary artery disease (CAD). Coronary physiology measurements have emerged for clinical decision making in interventional cardiology, but the focus lies mainly on epicardial vessels rather than the impact of these stenoses on the myocardial microcirculation. The latter can be quantified by measuring the coronary flow reserve (CFR), a combined pressure and flow index with a strong ability to predict clinical outcomes in CAD...
August 2018: European Cardiology
https://www.readbyqxmd.com/read/30309765/feasibility-of-dynamic-myocardial-ct-perfusion-using-single-source-64-row-ct
#2
Nobuo Tomizawa, Shengpu Chou, Yusuke Fujino, Masaru Kamitani, Kodai Yamamoto, Shinichi Inoh, Takeshi Nojo, Kanako K Kumamaru, Shigeki Aoki, Sunao Nakamura
BACKGROUND: Dynamic myocardial computed tomography perfusion (CTP) is an emerging technique to diagnose significant coronary stenosis. However, this procedure has not been reported using single-source 64-row CT. OBJECTIVE: To investigate the radiation dose and the diagnostic performance of dynamic CTP to diagnose significant stenosis by catheter exam. METHODS: We prospectively included 165 patients who underwent CTP exam under adenosine stress using a single-source 64-row CT...
October 6, 2018: Journal of Cardiovascular Computed Tomography
https://www.readbyqxmd.com/read/30306128/cross-talk-among-writers-readers-and-erasers-of-m-6-a-regulates-cancer-growth-and-progression
#3
Subbarayalu Panneerdoss, Vijay K Eedunuri, Pooja Yadav, Santosh Timilsina, Subapriya Rajamanickam, Suryavathi Viswanadhapalli, Nourhan Abdelfattah, Benjamin C Onyeagucha, Xiadong Cui, Zhao Lai, Tabrez A Mohammad, Yogesh K Gupta, Tim Hui-Ming Huang, Yufei Huang, Yidong Chen, Manjeet K Rao
The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m6 A levels by silencing either N 6 -adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m6 A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor-β signaling pathway genes...
October 2018: Science Advances
https://www.readbyqxmd.com/read/30293481/niraparib-a-promising-drug-with-hematological-toxicity
#4
Naga Sk Patibandla, Dulabh K Monga
Ovarian cancer is the second most common and the most lethal gynecological malignancy in the western world. Unfortunately, there are lack of methods for early screening and diagnosis of the disease. Because of this, most of the cases are diagnosed at an advanced stage and have poor prognosis. The standard treatment of ovarian cancer is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. There are new molecular agents available for maintenance therapy of ovarian cancer including anti-angiogenic therapies, poly adenosine diphosphate ribose polymerase inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches...
October 6, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/30269289/trimetaphosphate-activates-prebiotic-peptide-synthesis-across-a-wide-range-of-temperature-and-ph
#5
Izabela Sibilska, Yu Feng, Lingjun Li, John Yin
The biochemical activation of amino acids by adenosine triphosphate (ATP) drives the synthesis of proteins that are essential for all life. On the early Earth, before the emergence of cellular life, the chemical condensation of amino acids to form prebiotic peptides or proteins may have been activated by inorganic polyphosphates, such as tri metaphosphate (TP). Plausible volcanic and other potential sources of TP are known, and TP readily activates amino acids for peptide synthesis. But de novo peptide synthesis also depends on pH, temperature, and processes of solvent drying, which together define a varied range of potential activating conditions...
September 29, 2018: Origins of Life and Evolution of the Biosphere
https://www.readbyqxmd.com/read/30260294/clinical-pharmacokinetics-pharmacodynamics-safety-and-tolerability-of-jnj-54175446-a-brain-permeable-p2x7-antagonist-in-a-randomised-single-ascending-dose-study-in-healthy-participants
#6
Maarten Timmers, Paulien Ravenstijn, Liwen Xi, Gallen Triana-Baltzer, Maura Furey, Sandy Van Hemelryck, Jeike Biewenga, Marc Ceusters, Anindya Bhattacharya, Maarten van den Boer, Luc van Nueten, Peter de Boer
BACKGROUND: Central nervous system-derived interleukin-1β plays a role in mood disorders. P2X7 receptor activation by adenosine-triphosphate leads to the release of interleukin-1β. AIMS: This first-in-human study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics of a novel central nervous system-penetrant P2X7 receptor antagonist, JNJ-54175446, in healthy participants. METHODS: The study had three parts: an ascending-dose study in fasted participants (0...
September 27, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/30257492/impact-of-genetic-variability-on-physiological-responses-to-caffeine-in-humans-a-systematic-review
#7
REVIEW
Jacob L Fulton, Petros C Dinas, Andres E Carrillo, Jason R Edsall, Emily J Ryan, Edward J Ryan
Emerging research has demonstrated that genetic variation may impact physiological responses to caffeine consumption. The purpose of the present review was to systematically recognize how select single nucleotide polymorphisms (SNPs) impact habitual use of caffeine as well as the ergogenic and anxiogenic consequences of caffeine. Two databases (PubMed and EBSCO) were independently searched using the same algorithm. Selected studies involved human participants and met at least one of the following inclusion criteria: (a) genetic analysis of individuals who habitually consume caffeine; (b) genetic analysis of individuals who underwent measurements of physical performance with the consumption of caffeine; (c) genetic analysis of individuals who underwent measurements of mood with the consumption of caffeine...
September 25, 2018: Nutrients
https://www.readbyqxmd.com/read/30232916/istradefylline-for-the-treatment-of-parkinson-s-disease-is-it-a-promising-strategy
#8
Margherita Torti, Laura Vacca, Fabrizio Stocchi
Istradefylline (ISD) is a new drug developed for the treatment of Parkinson's disease (PD). It is an adenosine receptor A2A antagonists that will represent an important option for patients with advanced PD where it has been demonstrated efficacy in decreasing daily OFF time and is well tolerated. ISD has been marketed in Japan since May 2013. Areas covered: The objective of this review is to summarize evidences emerged from clinical studies that have demonstrated the efficacy of ISD in advanced parkinsonian patients...
September 20, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/30230598/physical-exercise-prevents-alterations-in-purinergic-system-and-oxidative-status-in-lipopolysaccharide-induced-sepsis-in-rats
#9
Vanessa Valéria Miron, Nathieli Bianchin Bottari, Charles Elias Assmann, Naiara Stefanello, Pauline da Costa, Luana Paula Pelinson, Karine Paula Reichert, Anielen Dutra da Silva, Thauan Faccin Lopes, Ivana Beatrice Mânica da Cruz, Jean Sévigny, Vera Maria Morsch, Maria Rosa Chitolina Schetinger, Andréia Machado Cardoso
Sepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti-inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS...
September 19, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30229580/deficiency-of-sphingosine-1-phosphate-reduces-the-expression-of-prohibitin-and-causes-%C3%AE-cell-impairment-via-mitochondrial-dysregulation
#10
Seok Woo Hong, Jinmi Lee, Hyemi Kwon, Se Eun Park, Eun Jung Rhee, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won Young Lee
BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB). METHODS: We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels...
September 2018: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30221577/streptococcus-suis-synthesizes-deoxyadenosine-and-adenosine-by-5-nucleotidase-to-dampen-host-immune-responses
#11
Jiao Dai, Liying Lai, Huanyu Tang, Weixue Wang, Shuoyue Wang, Chengping Lu, Huochun Yao, Hongjie Fan, Zongfu Wu
Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5'-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5'-nucleotidase not only enables producing 2'-deoxyadenosine from 2'-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2'-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses...
2018: Virulence
https://www.readbyqxmd.com/read/30199223/development-of-adenosine-a-2a-receptor-antagonists-for-the-treatment-of-parkinson-s-disease-a-recent-update-and-challenge
#12
Jiyue Zheng, Xiaohu Zhang, Xuechu Zhen
Parkinson's disease (PD) is a neurodegenerative disease with significant unmet medical needs. The current dopamine-centered treatments aim to restore motor functions of patients without slowing the disease progression. Long-term usage of these drugs is associated with diminished efficacy, motor fluctuation, and dyskinesia. Furthermore, the nonmotor features associated with PD such as sleep disorder, pain, and psychiatric symptoms are poorly addressed by the dopaminergic treatments. Adenosine receptor A2A antagonists have emerged as potential treatment for PD in the past decade...
September 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30184029/is-preoperative-clopidogrel-resistance-a-predictor-of-bleeding-and-risks-in-patients-undergoing-emergency-cabg-surgery
#13
Mehmet Kizilay, Zeynep Aslan, Unsal Vural, Ahmet Yavuz Balci, Ahmet Arif Aglar, Sahin Yilmaz
OBJECTIVE: The aims of this study were to determine whether the detection of preoperative clopidogrel resistance in patients undergoing cardiac surgery while using clopidogrel could play a guiding role in the prediction of postoperative excessive bleeding, transfusion requirements, and risks and to provide clinically significant data. METHODS: Two hundred and twenty-two patients [median age: 59.4 (38-83) years; 38 females] undergoing emergency and elective coronary artery bypass graft (CABG) surgeries in our clinic were evaluated prospectively...
July 2018: Brazilian Journal of Cardiovascular Surgery
https://www.readbyqxmd.com/read/30176535/cd73-inhibition-by-purine-cytotoxic-nucleoside-analogue-based-diphosphonates
#14
Charles Dumontet, Suzanne Peyrottes, Céline Rabeson, Emeline Cros-Perrial, Pierre Yves Géant, Laurent Chaloin, Lars Petter Jordheim
The ecto-5'-nucleotidase CD73 has emerged as an important drug target in oncoimmunology as well as in other diseases. We describe new ADP analogues as CD73 inhibitors based on the replacement of the adenosine moiety, in the reference inhibitor APCP, by purine nucleoside analogues. Compounds were assessed for CD73 inhibition both on purified recombinant protein and on CD73-expressing cancer cells. The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 μM (vs...
September 5, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30136629/downregulation-of-thioredoxin-1-in-the-ventral-tegmental-area-delays-extinction-of-methamphetamine-induced-conditioned-place-preference
#15
Mengbing Huang, Ming Bai, Zhimin Zhang, Lu Ge, Kang Lu, Xiang Li, Ye Li, Xiaoshuang Zhou, Ningning Guo, Lihua Yang, Jie Bai
BACKGROUND: Drug addiction is characterized by compulsive drug use and relapse. Thioredoxin-1 is emerging as an important modulator involved in the cellular protective response against a variety of toxic stressors. Previous study has reported that thioredoxin-1 overexpression prevents the acquisition of methamphetamine-conditioned place preference. Here, we aimed to investigate the effect of thioredoxin-1 on methamphetamine-conditioned place preference extinction and the possible mechanism...
September 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/30124146/emerging-and-alternative-therapies-for-parkinson-disease-an-updated-review
#16
Atul Kabra, Rohit Sharma, Ruchika Kabra, Uttam Singh Baghel
Parkinson's disease (PD) is one of the most common neurodegenerative disorder with intricate progressive pathology. Currently, available conventional options for PD have certain limitations of their own, and as a result, patient compliance and satisfaction are low. Current contemporary treatment options provide only symptomatic relief with limited control to prevent disease progression, resulting in poor patient compliance and satisfaction. Several emerging pharmacotherapies for PD are in different stages of clinical development...
August 20, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/30106110/silencing-of-pygb-suppresses-growth-and-promotes-the-apoptosis-of-prostate-cancer-cells-via-the-nf%C3%A2-%C3%AE%C2%BAb-nrf2-signaling-pathway
#17
Zhen Wang, Gang Han, Qinghong Liu, Wenyuan Zhang, Jinshan Wang
Brain‑type glycogen phosphorylase (PYGB) is an enzyme that metabolizes glycogen, whose function is to provide energy for an organism in an emergency state. The present study purposed to investigate the role and mechanism of PYGB silencing on the growth and apoptosis of prostate cancer cells. A cell counting kit‑8 assay and flow cytometry were performed to determine the cell viability, apoptosis and reactive oxygen species (ROS) content, respectively. Colorimetry was performed to analyze the activity of caspase‑3...
August 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30105585/regulation-of-human-brown-adipose-tissue-by-adenosine-and-a-2a-receptors-studies-with-15-o-h-2-o-and-11-c-tmsx-pet-ct
#18
Minna Lahesmaa, Vesa Oikonen, Semi Helin, Pauliina Luoto, Mueez U Din, Alexander Pfeifer, Pirjo Nuutila, Kirsi A Virtanen
PURPOSE: Brown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging...
August 13, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/30078187/how-to-influence-the-mesenchymal-stem-cells-fate-emerging-role-of-ectoenzymes-metabolizing-nucleotides
#19
REVIEW
Katarzyna Roszek, Magdalena Wujak
Extracellular purines, principally adenosine triphosphate and adenosine, are among the oldest evolutionary and widespread chemical messengers. The integrative view of purinergic signaling as a multistage coordinated cascade involves the participation of nucleotides/nucleosides, their receptors, enzymes metabolizing extracellular nucleosides and nucleotides as well as several membrane transporters taking part in the release and/or uptake of these molecules. In view of the emerging data, it is evident and widely accepted that an extensive network of diverse enzymatic activities exists in the extracellular space...
August 4, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30044259/unexpected-cardiac-mri-findings-in-patients-presenting-to-the-emergency-department-for-possible-acute-coronary-syndrome
#20
Cole E Ziegler, David M Painter, Joseph B Borawski, Raymond J Kim, Han W Kim, Alexander T Limkakeng
BACKGROUND: Stress cardiac magnetic resonance imaging (CMR) has become increasingly used in patients presenting to the emergency department (ED) with symptoms concerning for acute coronary syndrome (ACS). We hypothesized that CMR detects a number of alternative diagnoses (diagnoses other than ACS that could explain symptoms) and incidental findings in patients presenting to the ED for potential ACS. METHODS: We prospectively enrolled adult patients who presented to an academic ED from 2011 to 2015 for possible ACS and subsequently had an adenosine stress perfusion CMR as part of their diagnostic evaluation...
September 2018: Critical Pathways in Cardiology
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