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https://www.readbyqxmd.com/read/28415014/determination-and-quantification-of-intracellular-fludarabine-triphosphate-cladribine-triphosphate-and-clofarabine-triphosphate-by-lc-ms-ms-in-human-cancer-cells
#1
Jean-Yves Puy, Lars Petter Jordheim, Emeline Cros-Perrial, Charles Dumontet, Suzanne Peyrottes, Isabelle Lefebvre-Tournier
Purine nucleoside analogues are widely used in the treatment of haematological malignancies, and their biological activity is dependent on the intracellular accumulation of their triphosphorylated metabolites. In this context, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to study the formation of 5'-triphosphorylated derivatives of cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells. Br-ATP was used as internal standard. Separation was achieved on a hypercarb column...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#2
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28402245/thyroid-hormone-therapy-for-older-adults-with-subclinical-hypothyroidism
#3
David J Stott, Nicolas Rodondi, Patricia M Kearney, Ian Ford, Rudi G J Westendorp, Simon P Mooijaart, Naveed Sattar, Carole E Aubert, Drahomir Aujesky, Douglas C Bauer, Christine Baumgartner, Manuel R Blum, John P Browne, Stephen Byrne, Tinh-Hai Collet, Olaf M Dekkers, Wendy P J den Elzen, Robert S Du Puy, Graham Ellis, Martin Feller, Carmen Floriani, Kirsty Hendry, Caroline Hurley, J Wouter Jukema, Sharon Kean, Maria Kelly, Danielle Krebs, Peter Langhorne, Gemma McCarthy, Vera McCarthy, Alex McConnachie, Mairi McDade, Martina Messow, Annemarie O'Flynn, David O'Riordan, Rosalinde K E Poortvliet, Terence J Quinn, Audrey Russell, Carol Sinnott, Jan W A Smit, H Anette Van Dorland, Kieran A Walsh, Elaine K Walsh, Torquil Watt, Robbie Wilson, Jacobijn Gussekloo
Background The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. Methods We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment...
April 3, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28372926/epsilonproteobacteria-dominate-bacterial-diversity-at-a-natural-tar-seep
#4
Florence Lormières, Phil M Oger
The bacterial diversity of a naturally seeping bitumen source was investigated by 16S rRNA gene cloning and sequencing. Epsilonproteobacteria were shown to dominate the bacterial diversity in the underground water and within the bitumen, representing ca. 75% of the total bacterial diversity. These Epsilonproteobacteria were dominated by Sulfurimonas OTUs, while Sulfurovum and Arcobacter OTUs completed the remaining diversity. Epsilonproteobacteria are sulfur-oxidizer, nitrate-reducing chemo-lithoautotrophic bacteria, unable to use most organics for growth but capable of CO2 fixation...
March 31, 2017: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/28372509/fc%C3%AE-riib-expression-in-early-stage-chronic-lymphocytic-leukemia
#5
Rosa Bosch, Alba Mora, Eva Puy Vicente, Gerardo Ferrer, Sonia Jansà, Rajendra Damle, Sergey Gorlatov, Kanti Rai, Emili Montserrat, Josep Nomdedeu, Marta Pratcorona, Laura Blanco, Silvana Saavedra, Ana Garrido, Albert Esquirol, Irene Garcia, Miquel Granell, Rodrigo Martino, Julio Delgado, Jorge Sierra, Nicholas Chiorazzi, Carol Moreno
In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d...
April 4, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28358586/utility-of-microfluidic-devices-to-study-the-platelet-endothelium-interface
#6
Jevgenia Zilberman-Rudenko, Joanna L Sylman, Kathleen S Garland, Cristina Puy, Andrew D Wong, Peter C Searson, Owen J T McCarty
The integration of biomaterials and understanding of vascular biology has led to the development of perfusable endothelialized flow models, which have been used as valuable tools to study the platelet-endothelium interface under shear. In these models, the parameters of geometry, compliance, biorheology, and cellular complexity are varied to recapitulate the physical biology of platelet recruitment and activation under physiologically relevant conditions of blood flow. In this review, we summarize the mechanistic insights learned from perfusable microvessel models and discuss the potential utility as well as challenges of endothelialized microfluidic devices to study platelet function in the bloodstream in vitro...
March 30, 2017: Platelets
https://www.readbyqxmd.com/read/28325497/prognostic-factors-of-weight-loss-after-sleeve-gastrectomy-multi-centre-study-in-spain-and-portugal
#7
Raquel Sanchez Santos, Ricard Corcelles, Ramón Vilallonga Puy, Salvadora Delgado Rivilla, José Vicente Ferrer, Javier Foncillas Corvinos, Carlos Masdevall Noguera, Maria Socas Macias, Pedro Gomes, Carmen Balague Ponz, Jorge de Tomas Palacios, Sergio Ortiz Sebastian, Andrés Sanchez Pernaute, José Julián Puche Pla, Fátima Sabench Pereferrer, Julen Abasolo Vega, Xavier Suñol Sala, Ana Garcia Navarro, Carlos Duran Escribano, Norberto Cassinello Fernandez, Nieves Perez, José Antonio Gracia Solanas, Francisca Garcia-Moreno Nisa, Alberto Hernández Matias, Víctor Valentí Azcarate, José Eduardo Perez Folques, Inmaculada Navarro Garcia, Eduardo Dominguez-Adame Lanuza, Sagrario Martinez Cortijo, Jesús González Fernández
INTRODUCTION: Sleeve gastrectomy (SG) has become a technique in its own right although a selective or global indication remains controversial. The weight loss data at 5 years are heterogeneous. The aim of the study is to identify possible prognostic factors of insufficient weight loss after SG. METHODS: A SG retrospective multicenter study of more than one year follow-up was performed. Failure is considered if EWL>50%. Univariate and multivariate study of Cox regression were performed to identify prognostic factors of failure of weight loss at 1, 2 and 3 years of follow up...
March 18, 2017: Cirugía Española
https://www.readbyqxmd.com/read/28291557/terrace-landscapes-editorial-to-the-special-issue
#8
EDITORIAL
Andrea L Balbo, Arnald Puy
No abstract text is available yet for this article.
March 10, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28266656/size-and-stochasticity-in-irrigated-social-ecological-systems
#9
Arnald Puy, Rachata Muneepeerakul, Andrea L Balbo
This paper presents a systematic study of the relation between the size of irrigation systems and the management of uncertainty. We specifically focus on studying, through a stylized theoretical model, how stochasticity in water availability and taxation interacts with the stochastic behavior of the population within irrigation systems. Our results indicate the existence of two key population thresholds for the sustainability of any irrigation system: or the critical population size required to keep the irrigation system operative, and N* or the population threshold at which the incentive to work inside the irrigation system equals the incentives to work elsewhere...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257476/cardiac-iron-overload-in-chronically-transfused-patients-with-thalassemia-sickle-cell-anemia-or-myelodysplastic-syndrome
#10
Mariane de Montalembert, Jean-Antoine Ribeil, Valentine Brousse, Agnes Guerci-Bresler, Aspasia Stamatoullas, Jean-Pierre Vannier, Cécile Dumesnil, Agnès Lahary, Mohamed Touati, Krimo Bouabdallah, Marina Cavazzana, Emmanuelle Chauzit, Amandine Baptiste, Thibaud Lefebvre, Hervé Puy, Caroline Elie, Zoubida Karim, Olivier Ernst, Christian Rose
The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*<20 ms, in patients with thalassemia, SCA, or MDS...
2017: PloS One
https://www.readbyqxmd.com/read/28249145/gene-therapy-in-a-patient-with-sickle-cell-disease
#11
Jean-Antoine Ribeil, Salima Hacein-Bey-Abina, Emmanuel Payen, Alessandra Magnani, Michaela Semeraro, Elisa Magrin, Laure Caccavelli, Benedicte Neven, Philippe Bourget, Wassim El Nemer, Pablo Bartolucci, Leslie Weber, Hervé Puy, Jean-François Meritet, David Grevent, Yves Beuzard, Stany Chrétien, Thibaud Lefebvre, Robert W Ross, Olivier Negre, Gabor Veres, Laura Sandler, Sandeep Soni, Mariane de Montalembert, Stéphane Blanche, Philippe Leboulch, Marina Cavazzana
Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning...
March 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28158982/study-protocol-thyroid-hormone-replacement-for-untreated-older-adults-with-subclinical-hypothyroidism-a-randomised-placebo-controlled-trial-trust
#12
RANDOMIZED CONTROLLED TRIAL
David J Stott, Jacobijn Gussekloo, Patricia M Kearney, Nicolas Rodondi, Rudi G J Westendorp, Simon Mooijaart, Sharon Kean, Terence J Quinn, Naveed Sattar, Kirsty Hendry, Robert Du Puy, Wendy P J Den Elzen, Rosalinde K E Poortvliet, Jan W A Smit, J Wouter Jukema, Olaf M Dekkers, Manuel Blum, Tinh-Hai Collet, Vera McCarthy, Caroline Hurley, Stephen Byrne, John Browne, Torquil Watt, Douglas Bauer, Ian Ford
BACKGROUND: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. METHODS: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4...
February 3, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28143953/hemolytic-anemia-repressed-hepcidin-level-without-hepatocyte-iron-overload-lesson-from-g%C3%A3-nther-disease-model
#13
Sarah Millot, Constance Delaby, Boualem Moulouel, Thibaud Lefebvre, Nathalie Pilard, Nicolas Ducrot, Cécile Ged, Philippe Lettéron, Lucia de Franceschi, Jean Charles Deybach, Carole Beaumont, Laurent Gouya, Hubert De Verneuil, Saïd Lyoumi, Hervé Puy, Zoubida Karim
Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1...
February 2017: Haematologica
https://www.readbyqxmd.com/read/28124063/nucleic-acids-as-cofactors-for-factor-xi-and-prekallikrein-activation-different-roles-for-high-molecular-weight-kininogen
#14
Ivan Ivanov, Ruhama Shakhawat, Mao-Fu Sun, S Kent Dickeson, Cristina Puy, Owen J T McCarty, Andras Gruber, Anton Matafonov, David Gailani
The plasma zymogens factor XI (fXI) and prekallikrein (PK) are activated by factor XIIa (fXIIa) during contact activation. Polyanions such as DNA and RNA may contribute to thrombosis and inflammation partly by enhancing PK and fXI activation. We examined PK and fXI activation in the presence of nucleic acids, and determine the effects of the cofactor high molecular weight kininogen (HK) on the reactions. In the absence of HK, DNA and RNA induced fXI autoactivation. Proteases known to activate fXI (fXIIa and thrombin) did not enhance this process appreciably...
April 3, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28118224/acute-hepatic-and-erythropoietic-porphyrias-from-ala-synthases-1-and-2-to-new-molecular-bases-and-treatments
#15
Hana Manceau, Laurent Gouya, Hervé Puy
PURPOSE OF REVIEW: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies...
May 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28096032/creation-of-an-intensive-care-unit-and-organizational-changes-in-an-adult-emergency-department-impact-on-acute-stroke-management
#16
Laurent Puy, Chantal Lamy, Sandrine Canaple, Audrey Arnoux, Nicolas Laine, Ella Iacob, Jean-Marc Constans, Olivier Godefroy
BACKGROUND AND PURPOSE: Following the reorganization of a University Medical Center onto a single campus, an Intensive Care Unit was created within the adult Emergency Department (ED ICU). We assessed the effects of these organizational changes on acute stroke management and the intravenous administration of recombinant tissue plasminogen activator (IV rtPA), as characterized by the thrombolysis rate, door-to-needle time (DNT) and outcome at 3months. METHODS: Between October 2013 and September 2015, we performed a retrospective, observational, single-center, comparative study of patients admitted for ischemic stroke and treated with IV rtPA during two 321-day periods (before and after the creation of the ED ICU)...
January 10, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28042864/synthesis-and-antibacterial-evaluation-of-new-sulfone-derivatives-containing-2-aroxymethyl-1-3-4-oxadiazole-thiadiazole-moiety
#17
Shihu Su, Xia Zhou, Guoping Liao, Puying Qi, Linhong Jin
Sulfones are one of the most important classes of agricultural fungicides. To discover new lead compounds with high antibacterial activity, a series of new sulfone derivatives were designed and synthesized by introducing the aroxymethyl moiety into the scaffold of 1,3,4-oxadiazole/thiadiazole sulfones. Antibacterial activities against three phytopathogens (Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, Xanthomonas axonopodis pv. citri.) were assayed in vitro. As compared to the control of commercial fungicides and some reported sulfone fungicides, seven compounds 5I-1-5I-7 exerted remarkably higher activities with EC50 values ranging from 0...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28031405/a-variant-of-peptide-transporter-2-predicts-the-severity-of-porphyria-associated-kidney-disease
#18
Dimitri Tchernitchko, Quentin Tavernier, Jérôme Lamoril, Caroline Schmitt, Neila Talbi, Said Lyoumi, Anne-Marie Robreau, Zoubida Karim, Laurent Gouya, Eric Thervet, Alexandre Karras, Hervé Puy, Nicolas Pallet
CKD occurs in most patients with acute intermittent porphyria (AIP). During AIP, δ-aminolevulinic acid (ALA) accumulates and promotes tubular cell death and tubulointerstitial damage. The human peptide transporter 2 (PEPT2) expressed by proximal tubular cells mediates the reabsorption of ALA, and variants of PEPT2 have different affinities for ALA. We tested the hypothesis that PEPT2 genotypes affect the severity and prognosis of porphyria-associated kidney disease. We analyzed data from 122 individuals with AIP who were followed from 2003 to 2013 and genotyped for PEPT2 At last follow-up, carriers of the PEPT2*1*1 genotype (higher affinity variant) exhibited worse renal function than carriers of the lower affinity variants PEPT2*1/*2 and PEPT2*2/*2 (mean±SD eGFR: 54...
December 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27979315/quality-criteria-in-bariatric-surgery-consensus-review-and-recommendations-of-the-spanish-association-of-surgeons-and-the-spanish-society-of-bariatric-surgery
#19
Fátima Sabench Pereferrer, Eduardo Domínguez-Adame Lanuza, Ainitze Ibarzabal, María Socas Macias, Víctor Valentí Azcárate, Amador García Ruiz de Gordejuela, Francisca García-Moreno Nisa, Jesús González Fernández, Ramón Vilallonga Puy, Nuria Vilarrasa García, Raquel Sánchez Santos
Bariatric surgery has proven to be highly effective in controlling obesity and metabolic syndrome; the results of this surgery are not only expressed in terms of weight loss, but also in terms of resolution of comorbidities, improved quality of life and complications. The different parameters used to measure these outcomes require uniformity and reference patterns. Therefore, it is essential to identify those indicators and quality criteria that are helpful in defining the «best practice» principles in bariatric surgery...
December 12, 2016: Cirugía Española
https://www.readbyqxmd.com/read/27976148/innovative-bioguided-fractionation-of-cranberry-juice-for-candida-biofilm-treatment-and-infected-wound-healing
#20
L Boudesocque-Delaye, T Puy, M Girardot, A Lanoue, L Bazinet, C Bodet, C Imbert, C Enguehard-Gueiffier
No abstract text is available yet for this article.
December 2016: Planta Medica
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