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https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#1
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792338/molecular-mechanism-for-the-influence-of-gender-dimorphism-on-alcoholic-liver-injury-in-mice
#2
S-Q Li, P Wang, D-M Wang, H-J Lu, R-F Li, L-X Duan, S Zhu, S-L Wang, Y-Y Zhang, Y-L Wang
It is known that women develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. However, the detailed molecular mechanisms remain unclear. The precise mechanism responsible for the sex difference needs to be determined. Female and male mice were given ethanol by intragastric infusion every day for 4 weeks. The pathological changes were detected by hematoxylin-eosin, Sirius red, oil red O, periodic acid-Schiff, and Hochest33258 staining in the liver of female and male mice...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29790401/translational-gaps-in-animal-models-of-human-infusion-reactions-to-nanomedicines
#3
S Moein Moghimi, Dmitri Simberg
Adverse infusion reactions to regulatory approved nanomedicines in human subjects are idiosyncratic, but outwardly reproducible in pigs. A large body of evidence suggests that the porcine reactions are related to robust nanoparticle clearance by pulmonary intravascular macrophages (PIMs), and rapid release of arachidonate metabolites from these cells. Similar to pigs, other animals that have resident PIMs in their lungs also respond to intravenously injected particles, where rapid particle clearance by PIMs correlate with peak periods of cardiopulmonary distress...
May 2018: Nanomedicine
https://www.readbyqxmd.com/read/29788416/evaluation-of-rapid-vs-standard-infliximab-infusions-in-the-pediatric-population
#4
Nicole A Rozette, Christina M Hellauer, Chephra McKee, Turaj Vazifedan, Christos A Gabriel, James E Dice, Nancy U Yokois
Background: Rapid 1-hour infliximab infusions have been safely implemented in adults, but studies of these rapid infusions in pediatric patients are limited. This study's primary objective was to determine the safety of 1-hour infliximab infusions compared with standard 2- to 3-hour infusions in children with inflammatory bowel disease and other autoimmune disorders. Methods: We conducted an institutional review board-approved prospective study using an unmatched historical control group at a freestanding children's hospital comparing rapid vs standard infusion rates of infliximab and the use of premedications and immunomodulatory agents on the frequency of early and delayed infusion reactions...
May 18, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29784823/continuous-intrathecal-orexin-delivery-inhibits-cataplexy-in-a-murine-model-of-narcolepsy
#5
Mahesh K Kaushik, Kosuke Aritake, Aya Imanishi, Takashi Kanbayashi, Tadashi Ichikawa, Tetsuo Shimizu, Yoshihiro Urade, Masashi Yanagisawa
Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783034/vesicovaginal-fistula-repair-through-combined-transurethral-and-transvaginal-approaches-a-case-series-study
#6
Minkai Xie, Dachao Zheng, Haijun Yao, Zhong Wang
We report a case series study on five patients who underwent combined transurethral and transvaginal approaches to repair their vesicovaginal fistulas. All of them had failed the previous surgical treatments for their fistulas. Combined transurethral and transvaginal approaches successfully repaired their vesicovaginal fistulas, with minimal intraoperative bleeding and rapid postoperative recoveries. All the clinical symptoms had resolved. Bladder saline infusion tests and cystogram examinations confirmed the successful closure of their fistulas...
May 18, 2018: Journal of Gynecology Obstetrics and Human Reproduction
https://www.readbyqxmd.com/read/29781871/early-onset-of-diffuse-melanosis-cutis-under-pembrolizumab-therapy-illustrates-the-limitations-of-anti-pd-1-checkpoint-inhibitors
#7
Alexander Thiem, Patrick Schummer, Simon Ueberschaar, Andreas Kerstan, Hermann Kneitz, David Schrama, Silke Appenzeller, Svenja Meierjohann, Bastian Schilling, Matthias Goebeler, Anja Gesierich
Anti-PD-1 targeted immunotherapies have revolutionized the treatment of advanced melanoma and other tumor entities, and long disease-free intervals have been reported in responding patients. However, a considerable number of patients still progress rapidly after the start of anti-PD-1 antibodies. Here, we document two patients, 78 and 85-year old, who suffered from advanced BRAF-V600 wild-type melanoma and received pembrolizumab 2 mg/kg every 3 weeks as the first systemic treatment. After only one, respectively, two infusions of pembrolizumab, both patients developed melanuria and diffuse melanosis cutis (DMC) on sun-exposed areas of their skin...
May 17, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29780415/comparison-of-efficacy-and-safety-of-lispro-and-aspart-evaluated-by-continuous-glucose-monitoring-system-in-patients-with-newly-diagnosed-type-2-diabetes
#8
Bing-Li Liu, Guo-Ping Yin, Feng-Fei Li, Yun Hu, Jin-Dan Wu, Mao-Yuan Chen, Lei Ye, Xiao-Fei Su, Jian-Hua Ma
Objective: To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. Methods: This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group)...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29776826/recognition-of-sympathetic-crashing-acute-pulmonary-edema-scape-and-use-of-high-dose-nitroglycerin-infusion
#9
Samantha Paone, Leigha Clarkson, Billy Sin, Sheena Punnapuzha
Sympathetic Crashing Acute Pulmonary Edema (SCAPE), or flash pulmonary edema, is the extreme end of the acute pulmonary edema spectrum. A sympathetic surge occurs as a result of decreased systemic perfusion resulting in further increases in afterload, causing the patient to decompensate. Patients can decompensate quickly, therefore patients require rapid interventions. The use of high-dose nitroglycerin (HDN) has been a topic of interest as it is believed to achieve preload and afterload reduction. However, its use continues to be controversial due to concerns of drug induced hypotension, syncope or paresthesia...
May 10, 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29768964/effects-of-combined-spinal-epidural-analgesia-on-first-stage-of-labor-a-cohort-study
#10
Silvia Poma, Luigia Scudeller, Chiara Verga, Giorgio Mirabile, Barbara Gardella, Federica Broglia, Maria Ciceri, Marinella Fuardo, Simona Pellicori, Maddalena Gerletti, Silvia Zizzi, Elena Masserini, Maria Paola Delmonte, Giorgio Antonio Iotti
BACKGROUND: Neuraxial anesthesia is considered as the gold standard in the control labor of pain. Its variants are epidural analgesia and combined spinal-epidural analgesia. Few studies, as yet, have investigated the duration of labor as a primary outcome. Some authors have suggested that combined spinal-epidural analgesia may reduce labor duration but at the moment the benefit of shortening labor is uncertain. The main aim of this study was to compare combined spinal-epidural with epidural analgesia in terms of their effect on duration of stage I labor, maternal, and neonatal outcomes...
May 17, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29764543/-experimental-research-on-individual-specific-rapid-potassium-supplementation-strategy-for-fatal-severe-hypokalemia
#11
Yu Du, Yi Mou, Jin Liu
OBJECTIVE: To explore the effectiveness and safety of the individual-specific rapid potassium supplementation strategy, and to provide experimental basis for treating fatal severe hypokalemia. METHODS: An acute fatal severe hypokalemia model was reproduced in 20 healthy adult Japanese big ear white rabbits with half lethal dose (LD50) of barium chloride (BaCl2 ) solution 168 mg×5 mL-1 ×kg-1 . The rabbits were divided into conventional potassium supplementation group and individual-specific rapid potassium supplementation group according to random number table method with 10 rabbits in each group...
May 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29760663/suppression-of-urinary-voiding-by-conditional-high-frequency-stimulation-of-the-pelvic-nerve-in-conscious-rats
#12
Charly B J Brouillard, Jonathan J Crook, Pedro P Irazoqui, Thelma A Lovick
Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic nerve. Repeated voids were induced by continuous infusion of saline into the bladder (11.2 ml/h) via a T-piece in the line to the bladder catheter. In each animal tested ( n = 6) high frequency pelvic nerve stimulation (1-3 kHz, 1-2 mA sinusoidal waveform for 60 s) applied within 2 s of the onset of a sharp rise in bladder pressure signaling an imminent void was able to inhibit micturition. Voiding was modulated in three ways: (1) Suppression of voiding (four rats, n = 13 trials)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29757478/varying-the-rate-of-intravenous-cocaine-infusion-influences-the-temporal-dynamics-of-both-drug-and-dopamine-concentrations-in-the-striatum
#13
Ellie-Anna Minogianis, Waqqas M Shams, Omar S Mabrouk, Jenny-Marie T Wong, Wayne G Brake, Robert T Kennedy, Patrick du Souich, Anne-Noël Samaha
The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 versus 90-100 seconds promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5-90 seconds produces different rates of rise of brain drug concentrations, while producing similar peak concentrations...
May 14, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29754771/epstein-barr-virus-specific-cytokine-induced-killer-cells-for-treatment-of-epstein-barr-virus-related-malignant-lymphoma
#14
Lisa-Marie Pfeffermann, Verena Pfirrmann, Sabine Huenecke, Melanie Bremm, Halvard Bonig, Hans-Michael Kvasnicka, Thomas Klingebiel, Peter Bader, Eva Rettinger
BACKGROUND: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context. METHODS: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool...
May 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29748628/7t-1-h-mrs-in-major-depressive-disorder-a-ketamine-treatment-study
#15
Jennifer W Evans, Níall Lally, Li An, Ningzhi Li, Allison C Nugent, Dipavo Banerjee, Sam L Snider, Jun Shen, Jonathan P Roiser, Carlos A Zarate
The glutamatergic modulator ketamine has striking and rapid antidepressant effects in major depressive disorder (MDD), but its mechanism of action remains unknown. Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive method able to directly measure glutamate levels in vivo; in particular, glutamate and glutamine metabolite concentrations are separable by 1H-MRS at 7T. This double-blind, placebo-controlled, crossover study that included 1 H-MRS scans at baseline and at 24 h post ketamine and post-placebo infusions sought to determine glutamate levels in the pregenual anterior cingulate (pgACC) of 20 medication-free MDD subjects and 17 healthy volunteers (HVs) 24 h post ketamine administration, and to evaluate any other measured metabolite changes, correlates, or predictors of antidepressant response...
April 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29743313/ivig-promote-cross-tolerance-against-inflammatory-stimuli-in-vitro-and-in-vivo
#16
Ángeles Domínguez-Soto, Miriam Simón-Fuentes, Mateo de Las Casas-Engel, Víctor D Cuevas, María López-Bravo, Jorge Domínguez-Andrés, Paula Saz-Leal, David Sancho, Carlos Ardavín, Juliana Ochoa-Grullón, Silvia Sánchez-Ramón, Miguel A Vega, Angel L Corbí
IVIg is an approved therapy for immunodeficiency and for several autoimmune and inflammatory diseases. However, the molecular basis for the IVIg anti-inflammatory activity remains to be fully explained and cannot be extrapolated from studies on animal models of disease. We now report that IVIg impairs the generation of human monocyte-derived anti-inflammatory macrophages by inducing JNK activation and activin A production and limits proinflammatory macrophage differentiation by inhibiting GM-CSF-driven STAT5 activation...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29732161/rapid-onset-diabetic-ketoacidosis-secondary-to-nivolumab-therapy
#17
Senhong Lee, Aparna Morgan, Sonali Shah, Peter R Ebeling
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non-small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29727073/efficacy-safety-and-durability-of-repeated-ketamine-infusions-for-comorbid-posttraumatic-stress-disorder-and-treatment-resistant-depression
#18
C Sophia Albott, Kelvin O Lim, Miriam K Forbes, Christopher Erbes, Susanna J Tye, John G Grabowski, Paul Thuras, Tegan M Batres-Y-Carr, Joseph Wels, Paulo R Shiroma
OBJECTIVE: The present study examined the efficacy, safety, and durability of repeated ketamine infusions for the treatment of comorbid posttraumatic stress disorder (PTSD) and treatment-resistant depression (TRD) in a sample of veterans. METHODS: Individuals with comorbid DSM-5-defined PTSD and DSM-IV-defined major depressive disorder (N = 15) received 6 intravenous ketamine infusions (0.5 mg/kg) on a Monday-Wednesday-Friday schedule over a 12-day period from May 2015 to June 2016...
May 1, 2018: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29724899/the-dot1l-inhibitor-pinometostat-reduces-h3k79-methylation-and-has-modest-clinical-activity-in-adult-acute-leukemia
#19
Eytan M Stein, Guillermo Garcia-Manero, David A Rizzieri, Raoul Tibes, Jesus G Berdeja, Michael R Savona, Mojca Jongen-Lavrenic, Jessica K Altman, Blythe Thomson, Stephen J Blakemore, Scott R Daigle, Nigel J Waters, A Benjamin Suttle, Alicia Clawson, Roy Pollock, Andrei Krivtsov, Scott A Armstrong, Jorge DiMartino, Eric Hedrick, Bob Löwenberg, Martin S Tallman
Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m2 /day by continuous intravenous infusion in 28-day cycles...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29724318/-safety-of-a-60-minute-rituximab-rapid-infusion-protocol-for-adult-b-cell-lymphoma-patients-a-single-center-single-arm-clinical-trail
#20
Shuang Jiao Liu, Wei Meng, Yan Bin Zhang
Objective To investigate the safety of a 60-minute rituximab rapid infusion protocol in the maintenance therapy for Chinese B-cell lymphoma patients (including the elderly) and to discuss the feasibility of rituximab treatment in outpatient departments or daily wards. Methods This prospective study enrolled 820 patients diagnosed with B cell lymphoma in the Department of Hematology of Peking Union Medical College Hospital from February 2015 to July 2016. From the second chemotherapy cycle,rituximab was infused within 60 minutes (100 mg/h over the first 15 minutes and the remaining dose given over 45 minutes, there was no maximum infusion rate,and 700 mg/h was acceptable),and the adverse reactions were recorded...
April 28, 2018: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
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