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https://www.readbyqxmd.com/read/28346464/sympathetic-nervous-system-activity-and-anti-lipolytic-response-to-iv-glucose-load-in-subcutaneous-adipose-tissue-of-obese-and-obese-type-2-diabetic-subjects
#1
Uwe Schumann, Christopher P Jenkinson, Andreas Alt, Martina Zügel, Jürgen M Steinacker, Marion Flechtner-Mors
The study aim was to investigate the effect of endogenous insulin release on lipolysis in subcutaneous adipose tissue after adrenergic stimulation in obese subjects diagnosed with type 2 diabetes (T2D). In 14 obese female T2D subjects, or 14 obese non-T2D controls, glycerol concentration was measured in response to the α1,2,ß-agonist norepinephrine, the α1-agonist norfenefrine and the ß2-agonist terbutaline (each 10-4 M), using the microdialysis technique. After 60 minutes of stimulation, an intravenous glucose load (0...
2017: PloS One
https://www.readbyqxmd.com/read/28342934/mitochondrial-transplantation-from-animal-models-to-clinical-use-in-humans
#2
REVIEW
James D McCully, Douglas B Cowan, Sitaram M Emani, Pedro J Del Nido
Mitochondrial transplantation is a novel therapeutic intervention to treat ischemia/reperfusion related disorders. The method for mitochondrial transplantation is simple and rapid and can be delivered to the end organ either by direct injection or vascular infusion. In this review, we provide mechanistic and histological studies in large animal models and present data to show clinical efficacy in human patients.
March 22, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28342764/ketamine-as-a-rapid-acting-agent-for-suicidal-ideation-a-meta-analysis
#3
REVIEW
Francesco Bartoli, Ilaria Riboldi, Cristina Crocamo, Carmen Di Brita, Massimo Clerici, Giuseppe Carrà
The current systematic review and meta-analysis aimed at exploring acute effects of intravenous (IV) ketamine, an antagonist of N-methyl-D-aspartate (NMDA), in subjects with current suicidal ideation. We included clinical trials testing a single IV dose of ketamine and assessing changes in suicidal ideation within 4hours after treatment. Meta-analyses based on random-effects models, were carried out generating pooled standardized mean differences (SMDs) between endpoint and baseline scores. Heterogeneity among studies was estimated using the I(2) index...
March 22, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28337283/intracoronary-hypothermia-for-acute-myocardial-infarction-in-the-isolated-beating-pig-heart
#4
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
#5
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
https://www.readbyqxmd.com/read/28331868/a-novel-practical-equation-for-treatment-of-emergent-hypernatremia-and-dehydration-phase-in-infants
#6
Saba Ghaffary, Azadeh Moghaddas, Mehrnoush Dianatkhah
Serum sodium (Na) concentration more than 145 mmol/L is defined as hypernatremia. Hypernatremia carries an acute morbidity and mortality, especially in neonates and infants. Rapid correction of hypernatremia leads to severe cerebral damages, and seizure is the most common neurological complication of hypernatremia. Selection and calculation of an appropriate fluid and its amount is one of the tremendous challenges. It is important to choose the correct amount of suitable fluid and adjust rehydration rate. In this study, we have suggested practical equation to determine the amount of fluid that should be administered to the neonates and infants with hypernatremia...
January 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28330689/evaluation-of-methohexital-as-an-alternative-to-propofol-in-a-high-volume-outpatient-pediatric-sedation-service
#7
Nicholas E Jones, Michael S Kelleman, Harold K Simon, Jana A Stockwell, Courtney McCracken, Michael D Mallory, Pradip P Kamat
BACKGROUND: Propofol is a preferred agent for many pediatric sedation providers because of its rapid onset and short duration of action. It allows for quick turn around times and enhanced throughput. Occasionally, intravenous (IV) methohexital (MHX), an ultra-short acting barbiturate is utilized instead of propofol. OBJECTIVE: Describe the experience with MHX in a primarily propofol driven outpatient sedation program and to see if it serves as an acceptable alternative when propofol is not the preferred pharmacologic option...
March 8, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28324923/topotecan-vincristine-doxorubicin-in-stage-4-high-risk-neuroblastoma-patients-failing-to-achieve-a-complete-metastatic-response-to-rapid-cojec-a-siopen-study
#8
Loredana Amoroso, Giovanni Erminio, Guy Makin, Andrew Dj Pearson, Penelope Brock, Dominique Valteau-Couanet, Victoria Castel, Marlène Pasquet, Genevieve Laureys, Caroline Thomas, Roberto Luksch, Ruth Ladenstein, Riccardo Haupt, Alberto Garaventa
Purpose: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤3 abnormal skeletal areas on 123iodine-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate...
March 21, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28324159/hibernation-based-blood-loss-therapy-increases-survivability-of-lethal-hemorrhagic-shock-in-rats
#9
Cecilia E Perez de Lara Rodriguez, Lester R Drewes, Matthew T Andrews
A small-volume (1 ml/kg) resuscitation fluid based on metabolic adaptations in hibernating mammals was optimized using a rat model of hemorrhagic shock. A previous study of this therapy tested only one concentration of three specific components: 4 M D-stereoisomer of beta-hydroxybutyrate (BHB), 43 mM melatonin, and 20% DMSO. In this study, we considered the range of concentrations of BHB and melatonin seen during the physiological extremes of rapid arousal from hypothermic torpor in natural hibernators and applied these to the non-hibernating Sprague-Dawley rat model...
March 21, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28322027/rapid-differentiating-colorectal-cancer-and-colorectal-polyp-using-dried-blood-spot-mass-spectrometry-metabolomic-approach
#10
Yu Jing, Xue Wu, Peng Gao, Zhongze Fang, Jingjing Wu, Qingjun Wang, Chen Li, Zhitu Zhu, Yunfeng Cao
Colorectal cancer (CRC) is the third leading causes of cancer mortality, and the early-stage detection could significantly enhance survival rates. Cancer influences the important metabolic pathways and the changes in metabolite levels had been used in many studies as the potential biomarkers. This study is aimed at screening metabolite biomarkers with CRC diagnosis potentials. The direct infusion mass spectrometry (MS) metabolomic analysis based on dried blood spot was used to distinguish CRC from polyp. The target metabolites were composed of 23 amino acids and 26 acylcarnitines...
March 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28321983/chloroprocaine-for-epidural-anesthesia-in-infants-and-children
#11
REVIEW
Giorgio Veneziano, Joseph D Tobias
Continuous epidural infusions are an effective and safe method of providing anesthesia and postoperative analgesia in infants and children with multiple advantages over systemic medications, including earlier tracheal extubation, decreased perioperative stress response, earlier return of bowel function, and decreased exposure to volatile anesthetic agents with uncertain long-term neurocognitive effects. Despite these benefits, local anesthetic toxicity remains a concern in neonates and infants because of their decreased metabolic capacity for amide local anesthetics...
March 21, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28319488/an-in-vitro-assessment-of-the-efficacy-of-various-iv-cannulas-for-the-rapid-iv-fluid-administration
#12
Mineto Kamata, Hina Walia, Mumin Hakim, Dmitry Tumin, Joseph D Tobias
OBJECTIVES: The current study prospectively evaluates the administration of fluid through commonly used vascular cannulas of various length and diameter. DESIGN: Observational, in vitro experiment. SETTING: Not applicable. SUBJECTS: No human subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluid (500 mL) was administered via gravity flow and with pressure assistance (pressure bag set at 300 mm Hg) through various vascular cannulas including peripheral IV catheters (22 gauge, 1 inch; 20 gauge, 1...
March 17, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28303726/pharmacokinetic-and-pharmacodynamic-variability-of-insulin-when-administered-by-jet-injection
#13
Elsemiek E C Engwerda, Cees J Tack, Bastiaan E de Galan
BACKGROUND: Jet injection has been shown to accelerate the absorption and action of rapid-acting insulin. In this study, we compared the variability of absorption characteristics between jet injection and conventional administration of the rapid-acting insulin analogue aspart. METHODS: A total of 30 healthy volunteers were enrolled in this randomized controlled blinded parallel study. On two test days, they received insulin aspart (0.2 units/kg body weight), either by jet injection or conventional pen, followed by a 6-hour euglycemic glucose clamp...
March 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28296671/the-use-of-thrombolytic-therapy-in-the-treatment-of-frostbite-injury
#14
Allyson Wexler, Sarah Zavala
Frostbite can lead to severe consequences including loss of digits and limbs. One of the mechanisms of frostbite includes vascular thrombosis. The use of tissue plasminogen activator (tPA) in frostbite has been shown to be effective in case reports and small prospective studies. A retrospective chart review was performed on all patients admitted for frostbite between January 2008 and April 2015, and six patients were identified as having received treatment with intravenous tPA. Patients received an initial bolus dose followed by a 6-hour infusion of tPA...
March 3, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28289713/th17-cells-are-refractory-to-senescence-and-retain-robust-antitumor-activity-after-long-term-ex-vivo-expansion
#15
Jacob S Bowers, Michelle H Nelson, Kinga Majchrzak, Stefanie R Bailey, Baerbel Rohrer, Andrew D M Kaiser, Carl Atkinson, Luca Gattinoni, Chrystal M Paulos
Adoptive immunotherapy for solid tumors relies on infusing large numbers of T cells to mediate successful antitumor responses in patients. While long-term rapid-expansion protocols (REPs) produce sufficient numbers of CD8(+) T cells for treatment, they also cause decline in the cell's therapeutic fitness. In contrast, we discovered that IL-17-producing CD4(+) T cells (Th17 cells) do not require REPs to expand 5,000-fold over 3 weeks. Also, unlike Th1 cells, Th17 cells do not exhibit hallmarks of senescence or apoptosis, retaining robust antitumor efficacy in vivo...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289286/early-antibody-therapy-can-induce-long-lasting-immunity-to-shiv
#16
Yoshiaki Nishimura, Rajeev Gautam, Tae-Wook Chun, Reza Sadjadpour, Kathryn E Foulds, Masashi Shingai, Florian Klein, Anna Gazumyan, Jovana Golijanin, Mitzi Donaldson, Olivia K Donau, Ronald J Plishka, Alicia Buckler-White, Michael S Seaman, Jeffrey D Lifson, Richard A Koup, Anthony S Fauci, Michel C Nussenzweig, Malcolm A Martin
Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28282403/chemokine-binding-protein-m3-limits-atherosclerosis-in-apolipoprotein-e-mice
#17
Dhanya Ravindran, Anisyah Ridiandries, Laura Z Vanags, Rodney Henriquez, Siân Cartland, Joanne T M Tan, Christina A Bursill
Chemokines are important in macrophage recruitment and the progression of atherosclerosis. The 'M3' chemokine binding protein inactivates key chemokines involved in atherosclerosis (e.g. CCL2, CCL5 and CX3CL1). We aimed to determine the effect of M3 on plaque development and composition. In vitro chemotaxis studies confirmed that M3 protein inhibited the activity of chemokines CCL2, CCL5 and CX3CL1 as primary human monocyte migration as well as CCR2-, CCR5- and CX3CR1-directed migration was attenuated by M3...
2017: PloS One
https://www.readbyqxmd.com/read/28280971/a-phase-1-study-of-anti-tgf%C3%AE-receptor-type-ii-monoclonal-antibody-ly3022859-in-patients-with-advanced-solid-tumors
#18
Anthony W Tolcher, Jordan D Berlin, Jan Cosaert, John Kauh, Emily Chan, Sarina A Piha-Paul, Alex Amaya, Shande Tang, Kyla Driscoll, Richard Kimbung, S R Prasad Kambhampati, Ivelina Gueorguieva, David S Hong
PURPOSE: LY3022859 is an anti-TGFβRII IgG1 monoclonal antibody that inhibits receptor-mediated signaling activation. The primary objective of this phase I study was to determine a phase II dose in patients with advanced solid tumors. Secondary objectives were to assess safety and pharmacokinetics (PK). METHODS: LY3022859 was infused intravenously (IV) at 1.25 mg/kg over 1 h every 2 weeks (Q2W) (cohort 1A) and at flat doses of 12.5 mg (cohort 1B) and 25 mg (cohort 2) over 3 h Q2W...
March 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28280089/successful-transfer-of-umbilical-cord-blood-cd34-hematopoietic-stem-and-progenitor-derived-nk-cells-in-older-acute-myeloid-leukemia-patients
#19
Harry Dolstra, Mieke W H Roeven, Jan Spanholtz, Basav N Hangalapura, Marleen Tordoir, Frans Maas, Marij Leenders, Fenna Bohme, Nina Kok, Carel Trilsbeek, Jos Paardekooper, Anniek B van der Waart, Peter E Westerweel, Tjeerd J F Snijders, Jan J Cornelissen, Gerard M J Bos, Hans F M Pruijt, Aniek O De Graaf, Bert van der Reijden, Joop H Jansen, Arnold van der Meer, Gerwin Huls, Jeannette Cany, Frank Preijers, Nicole M A Blijlevens, Nicolaas M Schaap
PURPOSE: Older acute myeloid leukemia (AML) patients have a poor prognosis, therefore novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting an unique scalable NK cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPCs) from partially HLA-matched umbilical cord blood units. EXPERIMENTAL DESIGN: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30x10^6/kg body weight) after lymphodepleting chemotherapy without cytokine boosting...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28279967/ezetimibe-increases-endogenous-cholesterol-excretion-in-humans
#20
Xiaobo Lin, Susan B Racette, Lina Ma, Michael Wallendorf, Richard E Ostlund
OBJECTIVE: Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. APPROACH AND RESULTS: In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo...
March 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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