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https://www.readbyqxmd.com/read/28324452/a-review-of-ranibizumab-for-the-treatment-of-diabetic-retinopathy
#1
REVIEW
Michael W Stewart
INTRODUCTION: Laser photocoagulation has been the standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for several decades. The discovery of vascular endothelial growth factor (VEGF) and the subsequent determination of its critical role in the development DME and PDR has led to the development of VEGF inhibitory drugs. Ranibizumab was the first anti-VEGF drug approved for the treatment of both DME and diabetic retinopathy in eyes with DME. METHODS: Medline searches with the keywords "ranibizumab," "diabetic macular edema," and "proliferative diabetic retinopathy" were performed to identify pertinent pre-clinical studies and clinical trials...
March 21, 2017: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/28323919/steroids-regulate-cxcl4-in-the-human-endometrium-during-menstruation-to-enable-efficient-endometrial-repair
#2
J A Maybin, U Thiruchelvam, M Madhra, Ptk Saunders, Hod Critchley
Context: Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. Objective: To determine the presence/regulation of CXCL4 in the human endometrium, as a putative repair factor at menses. Patients/Setting: Endometrium was collected throughout the menstrual cycle from healthy women attending the gynecology department...
February 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323620/discovery-of-novel-determinants-of-endothelial-lineage-using-chimeric-heterokaryons
#3
Wing Tak Wong, Gianfranco Matrone, XiaoYu Tian, Simion Alin Tomoiaga, Kin Fai Au, Shu Meng, Sayumi Yamazoe, Daniel Sieveking, Kaifu Chen, David M Burns, James K Chen, Helen M Blau, John P Cooke
We wish to identify determinants of endothelial lineage. Murine embryonic stem cells (mESC) were fused with human endothelial cells in stable, non-dividing, heterokaryons. Using RNA-seq it is possible to discriminate between human and mouse transcripts in these chimeric heterokaryons. We observed a temporal pattern of gene expression in the ESCs of the heterokaryons that recapitulated ontogeny, with early mesodermal factors being expressed before mature endothelial genes. A set of transcriptional factors not known to be involved in endothelial development was upregulated, one of which was POU class 3 homeobox 2 (Pou3f2)...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28317673/effect-of-balanced-phacoemulsification-tip-on-the-outcomes-of-torsional-phacoemulsification-using-an-active-fluidics%C3%A2-system
#4
Sudarshan Khokhar, Neelima Aron, Sagnik Sen, Ganesh Pillay, Esha Agarwal
PURPOSE: To compare the outcomes of torsional phacoemulsification with a new balanced tip (Intrepid) and a conventional tip (Kelman) using a single active-fluidics torsional phacoemulsification machine (Centurion). SETTING: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. DESIGN: Prospective comparative case-control study. METHODS: Patients with senile cataract had torsional phacoemulsification with the Kelman conventional tip or the new Intrepid balanced tip using the active-fluidics torsional machine...
January 2017: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/28315462/implications-of-cerebrovascular-atp-binding-cassette-transporter-g1-abcg1-and-apolipoprotein-m-in-cholesterol-transport-at-the-blood-brain-barrier
#5
Alexandra Carmen Kober, Anil Paul Chirackal Manavalan, Carmen Tam-Amersdorfer, Andreas Holmér, Ahmed Saeed, Elham Fanaee Danesh, Martina Zandl, Nicole Maria Albrecher, Ingemar Björkhem, Gerhard M Kostner, Björn Dahlbäck, Ute Panzenboeck
Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315443/progesterone-modulates-diabetes-hyperglycemia-induced-changes-in-the-central-nervous-system-and-sciatic-nerve
#6
Fahim Atif, Megan C Prunty, Nefize Turan, Donald G Stein, Seema Yousuf
We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5 weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve...
March 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28315387/functional-role-of-ompf-and-ompc-porins-in-pathogenesis-of-avian-pathogenic-escherichia-coli
#7
Hassan M A Hejair, Yingchu Zhu, Jiale Ma, Yue Zhang, Zihao Pan, Wei Zhang, Huochun Yao
Avian pathogenic Escherichia coli is an important pathogen causes systemic infections in avian species and large economic losses in poultry industry worldwide. The functional role of porins during the infection and their mechanisms of interaction with host tissues for adhesion to and invasion are poorly understood. However, whether porins play a role in infection remains unclear. In this study we evaluated the potential of ompF and ompC outer membrane porins in the pathogenesis of avian pathogenic E. coli (APEC) strain TW-XM...
March 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28314760/loss-of-vegfb-and-its-signaling-in-the-diabetic-heart-is-associated-with-increased-cell-death-signaling
#8
Nathaniel Lal, Amy Pei-Ling Chiu, Fulong Wang, Dahai Zhang, Jocelyn Jia, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
VEGFB is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the release of this surface bound VEGFB, which triggers signaling pathways and gene expression to influence endothelial cell (autocrine action) and cardiomyocyte (paracrine effects) survival...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28306664/kr%C3%A3-ppel-like-factors-in-endothelial-cell-biology
#9
Eugene Chang, Lalitha Nayak, Mukesh K Jain
PURPOSE OF REVIEW: Krüppel-like factors (KLFs) are a family of transcription factors that regulate integral functions of endothelial cells including inflammation, proliferation, growth, apoptosis, cell differentiation and plasticity, and migration. This review will focus on the role of KLFs in physiological activity and their loss in vascular pathology. RECENT FINDINGS: New studies have pointed at the role of microRNAs as repressors of KLFs in atherosclerotic areas providing another level of signaling regulation of KLFs...
March 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28306601/assessing-the-impact-of-diabetes-mellitus-on-donor-corneal-endothelial-cell-density
#10
Chase A Liaboe, Benjamin T Aldrich, Pamela C Carter, Jessica M Skeie, Kimberlee A Burckart, Gregory A Schmidt, Cynthia R Reed, M Bridget Zimmerman, Mark A Greiner
PURPOSE: To quantify changes in endothelial cell density (ECD) of donor corneal tissue in relation to the presence or absence of a medical history of diabetes mellitus diagnosis, treatment, and complications. METHODS: A retrospective review was performed for all corneas collected at Iowa Lions Eye Bank between January 2012 and December 2015. For purposes of analysis, donor corneas were divided into 4 groups: nondiabetic, non-insulin-dependent diabetic, insulin-dependent diabetic without medical complications due to diabetes, and insulin-dependent diabetic with medical complications due to diabetes...
March 16, 2017: Cornea
https://www.readbyqxmd.com/read/28306600/modeling-endothelial-cell-loss-after-descemet-stripping-endothelial-keratoplasty-data-from-5-years-of-follow-up
#11
Mark A P Fajgenbaum, Emma J Hollick
PURPOSE: To report 5-year outcomes for graft survival and endothelial cell survival after Descemet stripping endothelial keratoplasty (DSEK) including regression modeling for cell survival over time. METHODS: This is a single-institution, retrospective, consecutive interventional series of 210 primary DSEK grafts operated for low-to-moderate risk indications, specifically Fuchs dystrophy and bullous keratopathy. Primary outcomes were cumulative graft survival and % endothelial cell loss from 3 months through 5 years; the secondary outcome was to trend endothelial cell density over time by least-squares and mixed nonlinear modeling...
March 16, 2017: Cornea
https://www.readbyqxmd.com/read/28306514/park2-depletion-connects-energy-and-oxidative-stress-to-pi3k-akt-activation-via-pten-s-nitrosylation
#12
Amit Gupta, Sara Anjomani-Virmouni, Nikos Koundouros, Maria Dimitriadi, Rayman Choo-Wing, Adamo Valle, Yuxiang Zheng, Yu-Hsin Chiu, Sameer Agnihotri, Gelareh Zadeh, John M Asara, Dimitrios Anastasiou, Mark J Arends, Lewis C Cantley, George Poulogiannis
PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all human cancers, and its depletion results in enhanced phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation and increased vulnerability to PI3K/Akt/mTOR inhibitors. PARK2 depletion contributes to AMPK-mediated activation of endothelial nitric oxide synthase (eNOS), enhanced levels of reactive oxygen species, and a concomitant increase in oxidized nitric oxide levels, thereby promoting the inhibition of PTEN by S-nitrosylation and ubiquitination...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28303370/comparison-of-graft-survival-following-penetrating-keratoplasty-and-descemet-s-stripping-endothelial-keratoplasty-in-eyes-with-a-glaucoma-drainage-device
#13
Shawn M Iverson, Oriel Spierer, George C Papachristou, William J Feuer, Wei Shi, David S Greenfield, Terrence P O'Brien
PURPOSE: To compare corneal graft survival rates after penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSEK) in patients with a glaucoma drainage device (GDD) or medically managed glaucoma. METHODS: A retrospective chart review was conducted on consecutive patients who underwent primary PK or primary DSEK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and a minimum of 6 months of follow-up...
March 16, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28302535/aqueous-humor-cytokines-in-patients-with-acute-non-arteritic-anterior-ischemic-optic-neuropathy-naion
#14
Jonathan A Micieli, Cindy Lam, Kinda Najem, Edward A Margolin
PURPOSE: To measure and compare the cytokine concentrations in the aqueous humor of patients with acute non-arteritic anterior ischemic optic neuropathy (NAION) and normal age-related cataract controls. DESIGN: Prospective, comparative observational study. METHODS: Aqueous humor samples were obtained in 10 patients with acute NAION (within 14 days of symptom onset) and 15 control patients with age-related cataract. The levels of 6 cytokines [vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-8] were determined using a multiplex bead immunoassay...
March 13, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28301547/epidermal-loss-of-g%C3%AE-q-confers-a-migratory-and-differentiation-defect-in-keratinocytes
#15
Colleen L Doçi, Constantinos M Mikelis, Juan Luis Callejas-Valera, Karina K Hansen, Alfredo A Molinolo, Asuka Inoue, Stefan Offermanns, J Silvio Gutkind
G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gαq and Gα11, activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Gα11 and Gαq from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα11/q signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28301412/large-silicone-droplets-after-intravitreal-bevacizumab-avastin
#16
Robert L Avery, Alessandro A Castellarin, Dilsher S Dhoot, Dante J Pieramici, Maʼan A Nasir, Nathan C Steinle, Logan P Avery, Gabriel M Gordon
PURPOSE: Despite its off-label status, intravitreal bevacizumab is the most commonly used intraocular anti-vascular endothelial growth factor agent. Regulation of compounding pharmacies has recently increased to make compounded pharmaceuticals safer. Despite these changes, a marked increase in symptomatic, large silicone oil droplets following intravitreal bevacizumab injections was noticed. METHODS: Retrospective chart review was performed. Within a single private practice, patients who were noted to have large or symptomatic silicone oil bubbles after an intravitreal injection were reviewed...
March 15, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28300679/px-18-protects-human-saphenous-vein-endothelial-cells-under-arterial-blood-pressure
#17
Koba Kupreishvili, Wim Stooker, Reindert W Emmens, Alexander B A Vonk, Jessica A Sipkens, Annemieke van Dijk, Leon Eijsman, Paul H Quax, Victor W M van Hinsbergh, Paul A J Krijnen, Hans W M Niessen
BACKGROUND: Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory Phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein. MATERIALS AND METHODS: The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n=6) perfused at arterial blood pressure with autologous blood for 6 hours...
March 11, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28299655/runx-family-genes-in-tissue-stem-cell-dynamics
#18
Chelsia Qiuxia Wang, Michelle Meng Huang Mok, Tomomasa Yokomizo, Vinay Tergaonkar, Motomi Osato
The Runx family genes play important roles in development and cancer, largely via their regulation of tissue stem cell behavior. Their involvement in two organs, blood and skin, is well documented. This review summarizes currently known Runx functions in the stem cells of these tissues. The fundamental core mechanism(s) mediated by Runx proteins has been sought; however, it appears that there does not exist one single common machinery that governs both tissue stem cells. Instead, Runx family genes employ multiple spatiotemporal mechanisms in regulating individual tissue stem cell populations...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28298524/novel-noncatalytic-substrate-selective-p38%C3%AE-specific-mapk-inhibitors-with-endothelial-stabilizing-and-anti-inflammatory-activity
#19
Nirav G Shah, Mohan E Tulapurkar, Aparna Ramarathnam, Amanda Brophy, Ramon Martinez, Kellie Hom, Theresa Hodges, Ramin Samadani, Ishwar S Singh, Alexander D MacKerell, Paul Shapiro, Jeffrey D Hasday
The p38 MAPK family is composed of four kinases of which p38α/MAPK14 is the major proinflammatory member. These kinases contribute to many inflammatory diseases, but the currently available p38 catalytic inhibitors (e.g., SB203580) are poorly effective and cause toxicity. We reasoned that the failure of catalytic p38 inhibitors may derive from their activity against noninflammatory p38 isoforms (e.g., p38β/MAPK11) and loss of all p38α-dependent responses, including anti-inflammatory, counterregulatory responses via mitogen- and stress-activated kinase (MSK) 1/2 and Smad3...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298215/nrf2-signaling-increases-expression-of-atp-binding-cassette-subfamily-c-mrna-transcripts-at-the-blood-brain-barrier-following-hypoxia-reoxygenation-stress
#20
Kathryn Ibbotson, Joshua Yell, Patrick T Ronaldson
BACKGROUND: Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model...
March 16, 2017: Fluids and Barriers of the CNS
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