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Gene therapy pain

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https://www.readbyqxmd.com/read/28079752/changes-in-dorsal-root-ganglion-gene-expression-in-response-to-spinal-cord-stimulation
#1
Dana M Tilley, David L Cedeño, Courtney A Kelley, Margaret DeMaegd, Ramsin Benyamin, Ricardo Vallejo
BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. METHODS: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours)...
January 11, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28058943/genome-wide-analysis-of-blood-gene-expression-in-migraine-implicates-immune-inflammatory-pathways
#2
Zachary F Gerring, Joseph E Powell, Grant W Montgomery, Dale R Nyholt
Background Typical migraine is a frequent, debilitating and painful headache disorder with an estimated heritability of about 50%. Although genome-wide association (GWA) studies have identified over 40 single nucleotide polymorphisms associated with migraine, further research is required to determine their biological role in migraine susceptibility. Therefore, we performed a study of genome-wide gene expression in a large sample of 83 migraine cases and 83 non-migraine controls to determine whether altered expression levels of genes and pathways could provide insights into the biological mechanisms underlying migraine...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28053302/polymyositis-without-beneficial-response-to-steroid-therapy-should-miyoshi-myopathy-be-a-differential-diagnosis
#3
Renata Siciliani Scalco, Paulo José Lorenzoni, David S Lynch, William Alves Martins, Heinz Jungbluth, Ros Quinlivan, Jefferson Becker, Henry Houlden
BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy...
January 5, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28050885/results-of-an-international-postmarketing-surveillance-study-of-pl-vegf165-safety-and-efficacy-in-210-patients-with-peripheral-arterial-disease
#4
Roman Deev, Igor Plaksa, Ilia Bozo, Artur Isaev
INTRODUCTION: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. pl-VEGF165, a gene therapy drug, was approved in Russia for the treatment of atherosclerotic peripheral arterial disease (PAD) after clinical studies in 2011. The study drug is an original gene construction in which pl-VEGF165 1...
January 3, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28044198/meloxicam-medication-reduces-orthodontically-induced-dental-root-resorption-and-tooth-movement-velocity-a-combined-in-vivo-and-in-vitro-study-of-dental-periodontal-cells-and-tissue
#5
Christian Kirschneck, Matthias Meier, Kathrin Bauer, Peter Proff, Jochen Fanghänel
Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions...
January 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28012326/a-case-report-of-desmoid-tumour-a-forgotten-aspect-of-fap
#6
Sarah Xuereb, Rachel Xuereb, Chiara Buhagiar, Jonathan Gauci, Claude Magri
INTRODUCTION: Desmoid tumours are locally aggressive tumours which are common in Familial Adenomatous Polyposis (FAP). PRESENTATION OF CASE: A 20-year old Familial Adenomatous Polyposis (FAP) patient presented with abdominal pain and distention. Abdominal imaging showed small bowel obstruction and hydronephrosis due to a pelvic mass. This mass showed significant enlargement on repeat imaging, and a diagnostic biopsy confirmed desmoid tumour. The mass was deemed unresectable and he was initially started on sulindac and raloxifene...
December 1, 2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28011039/the-direction-of-human-mesenchymal-stem-cells-into-the-chondrogenic-lineage-is-influenced-by-the-features-of-hydrogel-carriers
#7
A Hansson, A Wenger, H Barreto Henriksson, S Li, B R Johansson, H Brisby
Low back pain is a major public health issue in the Western world, one main cause is believed to be intervertebral disc (IVD) degeneration. To halt/diminish IVD degeneration, cell therapy using different biomaterials e.g. hydrogels as cell carriers has been suggested. In this study, two different hydrogels were examined (in vitro) as potential cell carriers for human mesenchymal stem cells (hMSCs) intended for IVD transplantation. The aim was to investigate cell-survival and chondrogenic differentiation of hMSCs when cultured in hydrogels Puramatrix(®) or Hydromatrix(®) and potential effects of stimulation with growth hormone (GH)...
December 13, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/28006774/the-prevalence-of-fabry-disease-in-patients-with-chronic-kidney-disease-in-turkey-the-turkfab-study
#8
Kultigin Turkmen, Aydın Guclu, Garip Sahin, Ismail Kocyigit, Levent Demirtas, Fatih Mehmet Erdur, Erkan Sengül, Oktay Ozkan, Habib Emre, Faruk Turgut, Hilmi Unal, Murat Karaman, Cengiz Acıkel, Hasan Esen, Ebru Balli, Gulfidan Bıtırgen, Halil Zeki Tonbul, Mahmut Ilker Yılmaz, Alberto Ortiz
BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy...
2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28003770/advances-in-the-management-of-erythropoietic-protoporphyria-role-of-afamelanotide
#9
REVIEW
Ashley M Lane, Jerome T McKay, Herbert L Bonkovsky
Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. In XLPP, the genetic defect is a gain-of-function mutation, usually a four-base deletion, in the gene that encodes the enzyme 5-aminolevulinic acid synthase-2, the first and rate-controlling enzyme of heme synthesis in developing red blood cells...
2016: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28003146/injectable-hyaluronic-acid-down-regulates-interferon-signaling-molecules-igfbp3-and-ifit3-in-the-bovine-intervertebral-disc
#10
Zepur Kazezian, Zhen Li, Mauro Alini, Sibylle Grad, Abhay Pandit
: Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socio-economic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and pro-apoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are up-regulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signaling pathway in the human annulus fibrosus (AF)...
December 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28002923/tendinopathic-supraspinatus-tenocytes-may-have-a-neuroendocrine-like-function-secreting-cgrp-sp-and-vegf-a-pilot-immunohistochemistry-study
#11
R Sahemey, P Malliaras, J S Lewis, G J Michael, P Shortland, D Morrissey, N Maffulli
We wanted to observe and compare the appearance of neurovascular tissue from tendon ex vivo, in patients with and without painful rotator cuff tendinopathy. Supraspinatus tendons were biopsied from 5 participants with painful tendinopathy and normal tendon from a young male. Slides were stained with haematoxylin and eosin and toluidine blue for histological assessment. Immunohistochemical markers for general nerves (protein gene-product 9.5 and synaptophysin), sensory nerves (calcitonin gene-related peptide; substance-P) and vascularisation (vascular endothelial growth factor) were used...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28001346/analgesic-microneedle-patch-for-neuropathic-pain-therapy
#12
Xi Xie, Conrado Pascual, Christopher Lieu, Seajin Oh, Ji Wang, Bende Zou, Julian Xie, Zhaohui Li, James Xie, David C Yeomans, Mei X Wu, Xinmin Simon Xie
Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/27993154/efficacy-and-safety-of-adult-human-bone-marrow-derived-cultured-pooled-allogeneic-mesenchymal-stromal-cells-stempeucel%C3%A2-preclinical-and-clinical-trial-in-osteoarthritis-of-the-knee-joint
#13
Pawan Kumar Gupta, Anoop Chullikana, Mathiyazhagan Rengasamy, Naresh Shetty, Vivek Pandey, Vikas Agarwal, Shrikant Yeshwant Wagh, Prasanth Kulapurathu Vellotare, Devi Damodaran, Pachaiyappan Viswanathan, Charan Thej, Sudha Balasubramanian, Anish Sen Majumdar
BACKGROUND: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. METHODS: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG)...
December 20, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27989333/inherited-pain-syndromes-and-ion-channels
#14
REVIEW
Francis J DiMario
Individuals rely on the perception of pain to avoid injury, to signal disease, and to warn about tissue inflammation and damage. However, the inheritance of inappropriate, extreme, or inadequate pain production is a source of significant human suffering. Substantial progress has been made in our understanding of the genetics and pathophysiology of pain through the study of individuals and families with several specific inherited pain syndromes. These studies have led to the discovery of a number of gene mutations associated with specific ion channel disturbances that produce familial inherited pain sensitivity and insensitivity syndromes...
August 2016: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/27986604/cell-therapy-for-the-degenerating-intervertebral-disc
#15
REVIEW
Wei Tong, Zhouyu Lu, Ling Qin, Robert L Mauck, Harvey E Smith, Lachlan J Smith, Neil R Malhotra, Martin F Heyworth, Franklin Caldera, Motomi Enomoto-Iwamoto, Yejia Zhang
Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy...
November 28, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27968705/efficient-nonviral-transfection-of-primary-intervertebral-disc-cells-by-electroporation-for-tissue-engineering-application
#16
Rahel D May, Adel Tekari, Daniela A Frauchiger, Anna Krismer, Lorin M Benneker, Benjamin Gantenbein
Low back pain (LBP) is an increasing global health problem associated with intervertebral disc (IVD) trauma and degeneration. Current treatment options include surgical interventions with partial unsatisfactory outcomes reported such as failure to relieve LBP, nonunions, nerve injuries, or adjacent segment disease. Cell-based therapy and tissue engineered IVD constructs supplemented with transfected disc cells that incorporate factors enhancing matrix synthesis represent an appealing approach to regenerate the IVD...
January 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27931749/-hereditary-epidermolysis-bullosa-french-national-guidelines-pnds-for-diagnosis-and-treatment
#17
C Chiaverini, E Bourrat, J Mazereeuw-Hautier, S Hadj-Rabia, C Bodemer, J-P Lacour
Hereditary epidermolysis bullosa (EB) is a heterogeneous group of rare genetic diseases characterized by fragile skin and/or mucous membrane, and it may be either local or generalized. It is caused by mutations in genes encoding different proteins involved mainly in the structure and function of the dermal-epidermal junction. Nineteen genes have so far been identified. They are classified by level of skin cleavage (from top to bottom) into four groups: EB simplex, junctional EB, dystrophic EB and Kindler syndrome...
December 5, 2016: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/27920806/hereditary-multiple-exostoses-a-review-of-clinical-appearance-and-metabolic-pattern
#18
REVIEW
Giovanni Beltrami, Gabriele Ristori, Guido Scoccianti, Angela Tamburini, Rodolfo Capanna
Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27917453/phase-i-study-of-mrx34-a-liposomal-mir-34a-mimic-administered-twice-weekly-in-patients-with-advanced-solid-tumors
#19
Muhammad S Beg, Andrew J Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G Bader, Sinil Kim, David S Hong
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial...
December 5, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#20
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
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