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https://www.readbyqxmd.com/read/27914945/effects-of-zacopride-a-moderate-ik1-channel-agonist-on-triggered-arrhythmia-and-contractility-in-human-ventricular-myocardium
#1
Mohammad T Elnakish, Benjamin D Canan, Ahmet Kilic, Peter J Mohler, Paul M L Janssen
Ventricular tachycardia is the leading cause of sudden arrhythmic death in the U.S. Recently, the moderate IK1 channel activator, zacopride, was shown to suppress triggered ventricular tachycardia in rats. Nonetheless, concerns were raised about the possibility of pro-arrhythmic activity after IK1 channel stimulation based on the promising anti-arrhythmic strategy of IK1 blockade in other animal models. Therefore, the goal of the current study was to investigate the ex-vivo effects of zacopride on triggered arrhythmia and contractility in ventricular human myocardium in order to validate data that was solely obtained from animal models...
November 30, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#2
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914450/mechanisms-of-inflammatory-injury-of-renal-tubular-cells-in-a-cellular-model-of-pyelonephritis
#3
M A Morosanova, E Y Plotnikov, L D Zorova, I B Pevzner, V A Popkov, D N Silachev, S S Jankauskas, V A Babenko, D B Zorov
Previously, we have assembled a cellular model of pyelonephritis which contains a primary culture of renal tubular epithelial cells, mononuclear leukocytes, and bacterial lysate or lipopolysaccharide. After cocultivation of renal cells with leukocytes and bacterial lysate, proinflammatory changes were observed in the renal cells, followed by nitrosative and oxidative stress and cell death. The interaction of bacterial antigens not only with leukocytes, but also with epithelial cells of the renal tubules, was partially mediated by signaling pathways involving Toll-like receptors (TLR2 and TLR4)...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913566/th2-responses-are-primed-by-skin-dendritic-cells-with-distinct-transcriptional-profiles
#4
Lisa M Connor, Shiau-Choot Tang, Emmanuelle Cognard, Sotaro Ochiai, Kerry L Hilligan, Samuel I Old, Christophe Pellefigues, Ruby F White, Deepa Patel, Adam Alexander T Smith, David A Eccles, Olivier Lamiable, Melanie J McConnell, Franca Ronchese
The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions...
December 2, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27913525/checkpoint-inhibition-in-myeloma
#5
Don M Benson
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#6
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912253/sex-and-age-differences-in-epinephrine-mechanisms-and-outcomes-after-brain-injury
#7
William M Armstead, John Riley, Monica S Vavilala
Traumatic brain injury (TBI) is the leading cause of injury related death in children, with boys and children under 4 years having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. Cerebral perfusion pressure can be normalized by use of vasoactive agents. The c-Jun-terminal kinase (JNK) isoform of mitogen activated protein kinase (MAPK) produces hemodynamic impairment after TBI, but less is known about its role in histopathology. We investigated whether epinephrine (EPI) age and sex dependently protected cerebral autoregulation and limited histopathology after TBI and the role of JNK in that outcome...
December 2, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#8
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911948/tlr3-induced-maturation-of-murine-dendritic-cells-regulates-ctl-responses-by-modulating-pd-l1-trafficking
#9
Aditi Varthaman, Hélène D Moreau, Mathieu Maurin, Philippe Benaroch
Targeting TLR3 through formulations of polyI:C is widely studied as an adjuvant in cancer immunotherapy. The efficacy of such targeting has been shown to increase in combination with anti-PD-L1 treatment. Nevertheless, the mechanistic details of the effect of polyI:C on DC maturation and the impact on T-DC interactions upon PD-L1 blockade is largely unknown. Here we found that although DC treatment with polyI:C induced a potent inflammatory response including the production of type I interferon, polyI:C treatment of DCs impaired activation of peptide specific CD8+ T cells mainly due to PD-L1...
2016: PloS One
https://www.readbyqxmd.com/read/27911934/efficacy-of-noninvasive-stellate-ganglion-blockade-performed-using-physical-agent-modalities-in-patients-with-sympathetic-hyperactivity-associated-disorders-a-systematic-review-and-meta-analysis
#10
Chun-De Liao, Jau-Yih Tsauo, Tsan-Hon Liou, Hung-Chou Chen, Chi-Lun Rau
BACKGROUND: Stellate ganglion blockade (SGB) is mainly used to relieve symptoms of neuropathic pain in conditions such as complex regional pain syndrome and has several potential complications. Noninvasive SGB performed using physical agent modalities (PAMs), such as light irradiation and electrical stimulation, can be clinically used as an alternative to conventional invasive SGB. However, its application protocols vary and its clinical efficacy remains controversial. This study investigated the use of noninvasive SGB for managing neuropathic pain or other disorders associated with sympathetic hyperactivity...
2016: PloS One
https://www.readbyqxmd.com/read/27911553/arbitrary-dicke-state-control-of-symmetric-rydberg-ensembles
#11
Tyler Keating, Charles H Baldwin, Yuan-Yu Jau, Jongmin Lee, Grant W Biedermann, Ivan H Deutsch
We study the production of arbitrary superpositions of Dicke states via optimal control. We show that N atomic hyperfine qubits, interacting symmetrically via the Rydberg blockade, are well described by the Jaynes-Cummings Hamiltonian and fully controllable by phase-modulated microwaves driving Rydberg-dressed states. With currently feasible parameters, it is possible to generate states of ∼ten hyperfine qubits in ∼1  μs, assuming a fast microwave phase switching time. The same control can be achieved with a "dressed-ground control" scheme, which reduces the demands for fast phase switching at the expense of increased total control time...
November 18, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#12
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27910862/methylphenidate-enhances-early-stage-sensory-processing-and-rodent-performance-of-a-visual-signal-detection-task
#13
Rachel L Navarra, Brian D Clark, Andrew T Gargiulo, Barry D Waterhouse
Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action impacts neural circuits performing cognitive and sensorimotor functions driving performance enhancement. The dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the cortex and is densely innervated by NE-containing fibers from the locus coeruleus (LC), a pathway known to modulate state-dependent sensory processing...
December 2, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#14
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#15
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27910088/the-efficacy-of-greater-occipital-nerve-blockade-in-chronic-migraine-a-placebo-controlled-study
#16
H L Gul, A O Ozon, O Karadas, G Koc, L E Inan
OBJECTIVE: GON blockade with local anesthetics is an effective treatment for a group of headaches, such as cervicogenic headache, cluster headache, occipital neuralgia, migraine. Our aim was to evaluate the efficacy of greater occipital nerve (GON) blockade in patients with chronic migraine (CM) by using a control group. MATERIALS AND METHODS: We included 44 CM patients and randomly divide the patients into two groups, as group A (bupivacaine) and group B (placebo) to our study...
December 2, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27909989/orexin-and-central-modulation-of-cardiovascular-and-respiratory-function
#17
Pascal Carrive, Tomoyuki Kuwaki
Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909985/il-25-blockade-inhibits-metastasis-in-breast-cancer
#18
Zhujun Jiang, Jingtao Chen, Xuemei Du, Hang Cheng, Xiaohu Wang, Chen Dong
Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4(+) T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung...
December 1, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27909967/selective-blockade-of-%C3%AE-2-adrenoceptor-subtypes-modulates-contractility-of-rat-myocardium
#19
T L Zefirov, L I Khisamieva, N I Ziyatdinova, A L Zefirov
The study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C- adrenoceptors applied in concentrations of 10(-9)-10(-5) M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D- and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles...
December 2, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#20
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
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