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https://www.readbyqxmd.com/read/27923070/macrophage-colony-stimulating-factor-derived-from-cd4-t-cells-contributes-to-control-of-a-blood-borne-infection
#1
Mary F Fontana, Gabrielly L de Melo, Chioma Anidi, Rebecca Hamburger, Chris Y Kim, So Youn Lee, Jennifer Pham, Charles C Kim
Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#2
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27906068/novel-use-of-cranial-epidural-space-in-rabbits-as-an-animal-model-to-investigate-bone-volume-augmentation-potential-of-different-bone-graft-substitutes
#3
Ivan Valdivia-Gandur, Wilfried Engelke, Víctor Beltrán, Eduardo Borie, Ramón Fuentes, María Cristina Manzanares-Céspedes
BACKGROUND: The success of bone augmentation to a major degree depends on the biomechanics and biological conditions of the surrounding tissues. Therefore, an animal model is needed providing anatomical sites with similar mechanical pressures for comparing its influence on different biomaterials for bone regeneration. The present report describes the new bone formation associated to biomaterial in a bursa created in the epidural space, between dura mater and cranial calvaria, under the constant pressure of cerebrospinal fluid...
December 1, 2016: Head & Face Medicine
https://www.readbyqxmd.com/read/27894066/obesity-associated-extracellular-mtdna-activates-central-tgf%C3%AE-pathway-to-cause-blood-pressure-increase
#4
Alberto Ale, Yalin Zhang, Cheng Han, Dongsheng Cai
Hypothalamic inflammation was recently found to mediate obesity-related hypertension, but the responsible upstream mediators remain unexplored. In this study, we show that dietary obesity is associated with extracellular release of mitochondrial DNA (mtDNA) into the cerebrospinal fluid, and that central delivery of mtDNA mimics TGFβ excess to activate downstream signaling pathways. Physiological study reveals that central administration of mtDNA or TGFβ are both sufficient to cause hypertension in mice. Knockout of the TGFβ receptor in pro-opiomelanocortin neurons counteracts the hypertensive effect of not only TGFβ but mtDNA excess, while the hypertensive action of central mtDNA can be blocked pharmacologically by a TGFβ receptor antagonist or genetically by TGFβ receptor knockout...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27890991/pulmonary-alveolar-proteinosis-experience-from-a-tertiary-care-center-and-systematic-review-of-indian-literature
#5
Vijay Hadda, Pawan Tiwari, Karan Madan, Anant Mohan, Nishkarsh Gupta, Sachidanand Jee Bharti, Vinod Kumar, Rakesh Garg, Anjan Trikha, Deepali Jain, Sudheer Arava, Gopi C Khilnani, Randeep Guleria
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by deposition of lipoproteinaceous material within alveoli, with a variable clinical course. Here, we report an experience of management of PAP at our center. A systematic review of previously reported cases from India is also included in the article. MATERIALS AND METHODS: This study included patients with primary PAP managed at our center from 2009 to 2015. Diagnosis of primary PAP was based on histopathologic diagnosis on bronchoalveolar lavage or transbronchial lung biopsy and absence of causes of secondary PAP...
November 2016: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/27886249/impairment-of-pdgf-induced-chemotaxis-by-extracellular-%C3%AE-synuclein-through-selective-inhibition-of-rac1-activation
#6
Taro Okada, Chihoko Hirai, Shaymaa Mohamed Mohamed Badawy, Lifang Zhang, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is characterized by α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies. Although it is known that extracellular α-Syn is detected in the plasma and cerebrospinal fluid, its physiological significance remains unclear. Here, we show that extracellular α-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the mutant α-Syn(A53T), found in hereditary PD, and the degree of inhibition was time-dependent, presumably because of the oligomerization of α-Syn...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864744/a-generic-multi-compartmental-cns-distribution-model-structure-for-9-drugs-allows-prediction-of-human-brain-target-site-concentrations
#7
Yumi Yamamoto, Pyry A Välitalo, Dirk-Jan van den Berg, Robin Hartman, Willem van den Brink, Yin Cheong Wong, Dymphy R Huntjens, Johannes H Proost, An Vermeulen, Walter Krauwinkel, Suruchi Bakshi, Vincent Aranzana-Climent, Sandrine Marchand, Claire Dahyot-Fizelier, William Couet, Meindert Danhof, Johan G C van Hasselt, Elizabeth C M de Lange
PURPOSE: Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human brain disposition. METHODS: A mathematical model consisting of several physiological brain compartments in the rat was developed using rich concentration-time profiles from nine structurally diverse drugs in plasma, brain extracellular fluid, and two cerebrospinal fluid compartments...
November 18, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27864367/phaseic-acid-an-endogenous-and-reversible-inhibitor-of-glutamate-receptors-in-mouse-brain
#8
Sheng T Hou, Susan X Jiang, L Irina Zaharia, Xiumei Han, Chantel L Benson, Jacqueline Slinn, Suzanne R Abrams
Phaseic acid (PA) is a phytohormone regulating important physiological functions in higher plants. Here, we show the presence of naturally occurring (-)-PA in mouse and rat brains. (-)-PA is exclusively present in the choroid plexus and the cerebral vascular endothelial cells. Purified (-)-PA has no toxicity and protects cultured cortical neurons against glutamate toxicity through reversible inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery (MCAO) elicited a significant induction in (-)-PA expression in the CSF, but not in the peripheral blood...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27857861/exploring-the-virchow-robin-spaces-function-a-unified-theory-of-brain-diseases
#9
Iype Cherian, Margarita Beltran, Ekkehard M Kasper, Binod Bhattarai, Sunil Munokami, Giovanni Grasso
BACKGROUND: Cerebrospinal fluid (CSF) transport across the central nervous system (CNS) is no longer believed to be on the conventional lines. The Virchow-Robin space (VRS) that facilitates CSF transport from the basal cisterns into the brain interstitial fluid (ISF) has gained interest in a whole new array of studies. Moreover, new line of evidence suggests that VRS may be involved in different pathological mechanisms of brain diseases. METHODS: Here, we review emerging studies proving the feasible role of VRS in sleep, Alzheimer's disease, chronic traumatic encephalopathy, and traumatic brain injury (TBI)...
2016: Surgical Neurology International
https://www.readbyqxmd.com/read/27852778/the-effects-of-peripheral-and-central-high-insulin-on-brain-insulin-signaling-and-amyloid-%C3%AE-in-young-and-old-app-ps1-mice
#10
Molly Stanley, Shannon L Macauley, Emily E Caesar, Lauren J Koscal, Will Moritz, Grace O Robinson, Joseph Roh, Jennifer Keyser, Hong Jiang, David M Holtzman
: Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APPswe/PS1dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27843772/long-term-evaluation-of-continuous-epidural-anesthesia-in-an-improved-canine-model
#11
Kyoko Sasauchi, Katsuhisa Sunada, Tatsuo Nakamura
BACKGROUND: Continuous epidural analgesia with catheterization is a useful technique, because it has a wide adaptation range and provides prolonged analgesia. Problems that may arise from long-term epidural analgesia are changes in the analgesic area, duration of analgesia and catheter-related problems. Few articles have evaluated gradual changes of long-term epidural analgesia. In the animal models used in those studies, the catheter was inserted by an invasive surgical procedure. In the present study, we evaluated changes in a canine model in which the catheter was inserted by a minimally invasive procedure...
August 2016: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/27843322/the-reduction-of-csf-tumor-necrosis-factor-alpha-levels-in-schizophrenia-no-correlations-with-psychopathology-and-coincident-metabolic-characteristics
#12
Haibing Zhu, Danfeng Wang, Xiuqin Liu
AIM: The aim of this study was to assess whether tumor necrosis factor alpha (TNF-α) levels are correlated with the behavioral syndrome of schizophrenia and/or metabolic abnormalities. METHODS: Sixty patients with first-onset schizophrenia were recruited. The concentrations of TNF-α in the cerebrospinal fluid (CSF) were determined in 22 schizophrenia patients and ten patients with nonsuppurative appendicitis using a radioimmunoassay. Physiological characteristics such as fasting blood glucose, fasting insulin, triglycerides, corrected QT interval, waist circumference, and body mass index were measured prior to CSF collection...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27836941/target-site-investigation-for-the-plasma-prolactin-response-mechanism-based-pharmacokinetic-pharmacodynamic-analysis-of-risperidone-and-paliperidone-in-the-rat
#13
Shinji Shimizu, Sandra M den Hoedt, Victor Mangas Sanjuan, Sinziana Cristea, Jana K Geuer, Dirk-Jan van den Berg, Robin Hartman, Francisco Bellanti, Elizabeth C M de Lange
In order to understand the drivers in the biological system response to dopamine D2 receptor antagonists, a mechanistic semi-physiologically-based (PB) pharmacokinetic-pharmacodymanic (PKPD) model was developed to describe prolactin responses to risperidone (RIS) and its active metabolite paliperidone (PAL). A microdialysis study in rats was performed to obtain detailed plasma, brain extracellular fluid (brainECF), and cerebrospinal fluid (CSF) concentrations of PAL and RIS. To assess the impact of P-gp functioning on brain distribution, experiments were performed in absence or presence of the P-glycoprotein (P-gp) inhibitor tariquidar (TQD)...
November 11, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27836940/spatial-model-of-convective-solute-transport-in-brain-extracellular-space-does-not-support-a-glymphatic-mechanism
#14
Byung-Ju Jin, Alex J Smith, Alan S Verkman
A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces...
December 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27832170/carotid-catheterization-and-automated-blood-sampling-induce-systemic-il-6-secretion-and-local-tissue-damage-and-inflammation-in-the-heart-kidneys-liver-and-salivary-glands-in-nmri-mice
#15
Anne Charlotte Teilmann, Björn Rozell, Otto Kalliokoski, Jann Hau, Klas S P Abelson
Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared...
2016: PloS One
https://www.readbyqxmd.com/read/27828999/cxcl4-and-cxcl4l1-differentially-affect-monocyte-survival-and-dendritic-cell-differentiation-and-phagocytosis
#16
Mieke Gouwy, Pieter Ruytinx, Egle Radice, Federico Claudi, Katrien Van Raemdonck, Raffaella Bonecchi, Massimo Locati, Sofie Struyf
Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine CXCL4 induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of CXCL4 and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC)...
2016: PloS One
https://www.readbyqxmd.com/read/27815445/neutrophil-necroptosis-is-triggered-by-ligation-of-adhesion-molecules-following-gm-csf-priming
#17
Xiaoliang Wang, Zhaoyue He, He Liu, Shida Yousefi, Hans-Uwe Simon
Apoptosis is the most common form of neutrophil death under both physiological and inflammatory conditions. However, forms of nonapoptotic neutrophil death have also been observed. In the current study, we report that human neutrophils undergo necroptosis after exposure to GM-CSF followed by the ligation of adhesion receptors such as CD44, CD11b, CD18, or CD15. Using a pharmacological approach, we demonstrate the presence of a receptor-interacting protein kinase-3 (RIPK3)-a mixed lineage kinase-like (MLKL) signaling pathway in neutrophils which, following these treatments, first activates p38 MAPK and PI3K, that finally leads to the production of high levels of reactive oxygen species (ROS)...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27813116/distinct-osteomimetic-response-of-androgen-dependent-and-independent-human-prostate-cancer-cells-to-mechanical-action-of-fluid-flow-prometastatic-implications
#18
Álvaro González, Cira García de Durango, Verónica Alonso, Beatriz Bravo, Arancha Rodríguez de Gortázar, Alan Wells, Jerónimo Forteza, Fernando Vidal-Vanaclocha
BACKGROUND AND METHODS: Prostate cancer frequently expresses an osteomimetic phenotype, but it is unclear how it is regulated and what biological and clinical implications it confers. Because mechanical forces physiologically regulate bone-remodeling activity in osteocytes, we hypothesized that mechanical action of fluid flow (MAFF) at the cancer microenvironment may similarly foster prostate cancer cell osteomimicry. RESULTS: We showed that in vitro MAFF on androgen-dependent (LNCap) and androgen-independent (PC3) prostate cancer cells remarkably increased OPG, VEGF, RunX2, PTH1R, and PTHrP gene expression in both cell lines irrespective of their androgen dependency...
November 3, 2016: Prostate
https://www.readbyqxmd.com/read/27799216/efavirenz-is-predicted-to-accumulate-in-brain-tissue-an-in-silico-in-vitro-and-in-vivo-investigation
#19
Paul Curley, Rajith K R Rajoli, Darren M Moss, Neill J Liptrott, Scott Letendre, Andrew Owen, Marco Siccardi
INTRODUCTION: Adequate concentrations of efavirenz in the central nervous system (CNS) are necessary to supress viral replication but high concentrations may increase the likelihood of CNS adverse drug reactions. The aim of this investigation was to evaluate efavirenz distribution into the cerebrospinal fluid (CSF) and brain using a physiologically based pharmacokinetic (PBPK) simulation for comparison with rodent and human data. METHODS: Efavirenz CNS distribution was calculated using a permeability-limited model in a virtual cohort of 100 patients receiving efavirenz (600 mg once-daily)...
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27798982/cerebrospinal-fluid-hypersecretion-in-pediatric-hydrocephalus
#20
Jason K Karimy, Daniel Duran, Jamie K Hu, Charuta Gavankar, Jonathan R Gaillard, Yasar Bayri, Hunter Rice, Michael L DiLuna, Volodymyr Gerzanich, J Marc Simard, Kristopher T Kahle
Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis...
November 2016: Neurosurgical Focus
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