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https://www.readbyqxmd.com/read/28438904/loss-of-resistance-to-angiotensin-ii-induced-hypertension-in-the-jackson-laboratory-recombination-activating-gene-null-mouse-on-the-c57bl-6j-background
#1
Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert C Speth, Kathryn Sandberg
Resistance to angiotensin II (Ang II)-induced hypertension in T-cell-deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1(-)(/-) -M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6...
April 24, 2017: Hypertension
https://www.readbyqxmd.com/read/28434161/can-valproic-acid-regulate-neurogenesis-from-nestin-cells-in-the-adult-midbrain
#2
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) causes the motor symptoms (e.g. tremor, muscle rigidity, bradykinesia, postural instability) of Parkinson's disease (PD). It is generally agreed that replacing these neurons will provide better motor symptom relief and fewer side effects than current pharmacotherapies. One potential approach to this is up-regulating endogenous DA neurogenesis in SNc. In the present study, we conducted bioinformatics analyses to identify signalling pathways that control expression of Pax6 and Msx1 genes, which have been identified as potentially important neurogenic regulators in the adult midbrain...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28433630/loss-of-murc-cavin-4-induces-jnk-and-mmp-9-activity-enhancement-in-vascular-smooth-muscle-cells-and-exacerbates-abdominal-aortic-aneurysm
#3
Kotaro Miyagawa, Takehiro Ogata, Tomomi Ueyama, Takeru Kasahara, Naohiko Nakanishi, Daisuke Naito, Takuya Taniguchi, Tetsuro Hamaoka, Naoki Maruyama, Masahiro Nishi, Taizo Kimura, Hiroyuki Yamada, Hiroki Aoki, Satoaki Matoba
Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC(-/-)) mice subjected to periaortic application of CaCl2 developed AAAs...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#4
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28430714/ultrasound-molecular-imaging-of-inflammation-in-mouse-abdominal-aorta
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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