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https://www.readbyqxmd.com/read/28430714/ultrasound-molecular-imaging-of-inflammation-in-mouse-abdominal-aorta
#1
Shiying Wang, Sunil Unnikrishnan, Elizabeth B Herbst, Alexander L Klibanov, Frank William Mauldin, John A Hossack
OBJECTIVES: The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively...
April 20, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28428057/natural-killer-cells-differentiated-in-vitro-from-cord-blood-cd34-cells-are-more-advantageous-for-use-as-an-immunotherapy-than-peripheral-blood-and-cord-blood-natural-killer-cells
#2
Anna Domogala, Michael Blundell, Adrian Thrasher, Mark W Lowdell, J Alejandro Madrigal, Aurore Saudemont
BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity...
April 17, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#3
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28417527/effects-of-dapagliflozin-on-insulin-requirement-glucose-excretion-and-%C3%A3-hydroxybutyrate-levels-are-not-related-to-baseline-hba1c-in-youth-with-type-1-diabetes
#4
Torben Biester, Baerbel Aschemeier, Maryam Fath, Marcel Frey, Markus F Scheerer, Olga Kordonouri, Thomas Danne
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into three baseline HbA1c categories (<7.5%, 7.5 to 9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels between 160-220 mg/dl...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28411247/exosomal-microrna-transfer-into-macrophages-mediates-cellular-postconditioning
#5
Geoffrey de Couto, Romain Gallet, Linda Cambier, Ervin Jaghatspanyan, Nupur Makkar, James Frederick Dawkins, Benjamin P Berman, Eduardo Marbán
BACKGROUND: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction (MI) via distinctive macrophage (MΦ) polarization. Here we demonstrate that CDC-secreted exosomes (CDCexo) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning. METHODS: Rats and pigs underwent MI induced by ischemia-reperfusion prior to intracoronary infusion of CDCexo, inert fibroblast exosomes (Fbexo; control), or vehicle. Two days later, infarct size was quantified...
April 14, 2017: Circulation
https://www.readbyqxmd.com/read/28411231/angiotensin-1-7-attenuates-angiotensin-ii-induced-cardiac-hypertrophy-via-a-sirt3-dependent-mechanism
#6
Lirong Guo, Ankang Yin, Qi Zhang, Tiecheng Zhong, Stephen T O'Rourke, Chengwen Sun
The objectives of the current study were to investigate the effect of Ang-(1-7) on the development of cardiac hypertrophy, and to identify the intracellular mechanism underlying this action of Ang-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), Ang II, Ang-(1-7), or Ang II+Ang-(1-7) for 4 weeks in normotensive rats. Chronic administration of Ang-(1-7) did not affect either basal blood pressure or the Ang II-induced elevation in blood pressure...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28404894/induction-and-characterization-of-anti-tumor-endothelium-immunity-elicited-by-vallovax-therapeutic-cancer-vaccine
#7
Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari
ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403018/prophylactic-atropine-administration-attenuates-the-negative-haemodynamic-effects-of-induction-of-anaesthesia-with-propofol-and-high-dose-remifentanil-a-randomised-controlled-trial
#8
Marieke Poterman, Thomas W L Scheeren, Marieke I van der Velde, Pieter L Buisman, Silvie Allaert, Michel M R F Struys, Alain F Kalmar
BACKGROUND: Induction of anaesthesia with propofol and remifentanil often induces unwanted bradycardia and hypotension, raising concerns regarding tissue oxygenation. The electrophysiological cardiac effects of remifentanil can be reversed by atropine. OBJECTIVE: To investigate if prophylactic administration of atropine can attenuate the negative haemodynamic effects of propofol and a high dose of remifentanil during induction of anaesthesia. DESIGN: A double-blind, randomised controlled trial...
April 11, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28402392/caveolae-localized-l-type-ca2-channels-do-not-contribute-to-function-or-hypertrophic-signalling-in-the-mouse-heart
#9
Robert N Correll, Catherine A Makarewich, Hongyu Zhang, Chen Zhang, Michelle A Sargent, Allen J York, Remus M Berretta, Xiongwen Chen, Steven R Houser, Jeffery D Molkentin
Aims: L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t-tubules where they initiate excitation-contraction coupling. Our recent work has shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae of adult feline cardiomyocytes can also generate a Ca2+ microdomain that activates nuclear factor of activated T-cells signaling and cardiac hypertrophy, although the relevance of this paradigm to hypertrophy regulation in vivo has not been examined...
April 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28401863/real-life-experience-with-a-new-anticoagulation-regimen-for-patients-undergoing-left-sided-ablation-procedures
#10
Charles Dussault, Santiago Rivera, Mariano Badra-Verdu, Felix Ayala-Paredes, Jean-François Roux
BACKGROUND: Current guidelines for anticoagulation during left-sided procedures recommend the administration of unfractionated heparin (UFH) with an initial bolus of 50-100 U/kg, followed by continuous infusion to maintain an activated clotting time (ACT) ≥ 300 s. Our objective was to compare the effectiveness of this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg bolus). METHODS: We collected data on a series of consecutive patients undergoing left sided ablation procedures...
November 2016: Indian Pacing and Electrophysiology Journal
https://www.readbyqxmd.com/read/28375159/local-gabaergic-signaling-within-sensory-ganglia-controls-peripheral-nociceptive-transmission
#11
Xiaona Du, Han Hao, Yuehui Yang, Sha Huang, Caixue Wang, Sylvain Gigout, Rosmaliza Ramli, Xinmeng Li, Ewa Jaworska, Ian Edwards, Jim Deuchars, Yuchio Yanagawa, Jinlong Qi, Bingcai Guan, David B Jaffe, Hailin Zhang, Nikita Gamper
The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain...
April 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28373005/avelumab-for-patients-with-previously-treated-metastatic-or-recurrent-non-small-cell-lung-cancer-javelin-solid-tumor-dose-expansion-cohort-of-a-multicentre-open-label-phase-1b-trial
#12
James L Gulley, Arun Rajan, David R Spigel, Nicholas Iannotti, Jason Chandler, Deborah J L Wong, Joseph Leach, W Jeff Edenfield, Ding Wang, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, Jean-Marie Cuillerot, Karen Kelly
BACKGROUND: Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). METHODS: In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA...
March 31, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28368937/physician-directed-versus-computerized-closed-loop-control-of-blood-pressure-using-phenylephrine-in-a-swine-model
#13
Nicole Ribeiro Marques, William E Whitehead, Upendar R Kallu, Michael P Kinsky, Joe S Funston, Taoufik Wassar, Muzna N Khan, Mindy Milosch, Daniel Jupiter, Karolos Grigoriadis, George C Kramer
BACKGROUND: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required...
March 31, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28368936/closed-loop-feedback-computer-controlled-phenylephrine-for-maintenance-of-blood-pressure-during-spinal-anesthesia-for-cesarean-delivery-a-randomized-trial-comparing-automated-boluses-versus-infusion
#14
Warwick D Ngan Kee, Yuk-Ho Tam, Kim S Khaw, Floria F Ng, Shara W Y Lee
BACKGROUND: We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions. METHODS: Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses...
March 31, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28364225/comparison-of-ambient-and-atmospheric-pressure-ion-sources-for-cystic-fibrosis-exhaled-breath-condensate-ion-mobility-mass-spectrometry-metabolomics
#15
Xiaoling Zang, José J Pérez, Christina M Jones, María Eugenia Monge, Nael A McCarty, Arlene A Stecenko, Facundo M Fernández
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted...
March 31, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28364198/drug-induced-sleep-endoscopy-with-target-controlled-infusion-using-propofol-and-monitored-depth-of-sedation-to-determine-treatment-strategies-in-obstructive-sleep-apnea
#16
Clemens Heiser, Phillippe Fthenakis, Alexander Hapfelmeier, Sebastian Berger, Benedikt Hofauer, Winfried Hohenhorst, Eberhard F Kochs, Klaus J Wagner, Guenther M Edenharter
BACKGROUND: Drug-induced sleep endoscopy (DISE) has become an important diagnostic examination tool in the treatment decision process for surgical therapies in the treatment of obstructive sleep apnea (OSA). Currently, there is a variety of regimes for the performance of DISE, which renders comparison and assessment across results difficult. It remains unclear how the different regimes influence the findings of the examination and the resulting conclusions and treatment recommendations...
March 31, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28363695/in-vitro-anaerobic-pharmacokinetic-pharmacodynamic-model-to-simulate-the-bactericidal-activity-of-levornidazole-against-bacteroides-fragilis
#17
Jiali Hu, Jing Zhang, Yuancheng Chen, Wang Liang, Shi Wu
PURPOSE: This study was designed to correlate the pharmacokinetic/pharmacodynamic (PK/PD) parameters with PD indices of levornidazole against Bacteroides fragilis and to calculate the PK/PD target value for levornidazole to attain its expected maximal bactericidal effect using an in vitro anaerobic dynamic PK/PD model. METHODS: An anaerobic dynamic PK/PD model was developed in vitro. The scheme for PK modeling was designed according to the PK parameters of levornidazole in the human body...
March 28, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28359342/measuring-the-impact-of-ambulatory-red-blood-cell-transfusion-on-home-functional-status-study-protocol-for-a-pilot-randomized-controlled-trial
#18
Dennis H Murphree, Theresa N Kinard, Nandita Khera, Curtis B Storlie, Che Ngufor, Sudhindra Upadhyaya, Jyotishman Pathak, Emma Fortune, Eapen K Jacob, Rickey E Carter, Karl A Poterack, Daryl J Kor
BACKGROUND: Red blood cell (RBC) transfusion is frequently employed in both ambulatory and hospital environments with the aim of improving patient functional status. In the ambulatory setting, this practice is particularly common in patients with malignancy due to anemia associated with their cancer therapy. Increasingly, the efficacy of this US$10.5 billion per year practice has been called into question. While it is often standard of care for patients with chemotherapy-induced anemia to receive ambulatory RBC transfusions, it is unclear to what extent such transfusions affect home functional status...
March 31, 2017: Trials
https://www.readbyqxmd.com/read/28337283/intracoronary-hypothermia-for-acute-myocardial-infarction-in-the-isolated-beating-pig-heart
#19
Luuk C Otterspoor, Lokien X van Nunen, Tilaï T Rosalina, Marcel Van't Veer, Sjoerd Van Tuijl, Marco Stijnen, Marcel Cm Rutten, Frans N van de Vosse, Nico Hj Pijls
Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336726/proteomic-signature-of-acute-liver-failure-from-discovery-and-verification-in-a-pig-model-to-confirmation-in-humans
#20
Jie Wang, Zeyu Sun, Jing Jiang, Daxian Wu, Xiaoli Liu, Zhongyang Xie, Ermei Chen, Danhua Zhu, Chao Ye, Xiaoqian Zhang, Wenqian Chen, Hongcui Cao, Lanjuan Li
Acute liver failure (ALF) is a fatal condition hallmarked by rapid development. The present study aimed to describe the dynamic alterations of serum proteins associated with ALF development, and to seek for novel biomarkers of ALF. Miniature pigs (n=30) were employed to establish ALF models by infusing D-galactosamine (GALN, 1.3g/kg). A total of 1589 serum proteins were compared in pooled serum samples (n=10) before and 36 hours after GALN administration through label-free quantitation (LFQ) based shotgun proteomics...
March 23, 2017: Molecular & Cellular Proteomics: MCP
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