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Gene therapy chronic pain

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https://www.readbyqxmd.com/read/29789638/human-carbonic-anhydrase-8-aav8-gene-therapy-inhibits-nerve-growth-factor-signaling-producing-prolonged-analgesia-and-anti-hyperalgesia-in-mice
#1
Gerald Z Zhuang, Udita Upadhyay, Xiaoying Tong, Yuan Kang, Diana M Erasso, Eugene S Fu, Konstantinos D Sarantopoulos, Eden R Martin, Tim Wiltshire, Luda Diatchenko, Shad B Smith, William Maixner, Roy C Levitt
Carbonic anhydrase-8 (Car8; murine gene symbol) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates neuronal intracellular calcium release. We previously reported that wild-type Car8 overexpression corrects the baseline allodynia and hyperalgesia associated with calcium dysregulation in the waddle (wdl) mouse due to a 19 bp deletion in exon 8 of the Car8 gene. In this report, we provide preliminary evidence that overexpression of the human wild-type ortholog of Car8 (CA8 WT ), but not the reported CA8 S100P loss-of-function mutation (CA8 MT ), inhibits nerve growth factor (NGF)-induced phosphorylation of ITPR1, TrkA (NGF high-affinity receptor), and ITPR1-mediated cytoplasmic free calcium release in vitro...
April 24, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29781145/core-outcome-set-for-gene-therapy-in-haemophilia-results-of-the-corehem-multistakeholder-project
#2
A Iorio, M W Skinner, E Clearfield, D Messner, G F Pierce, M Witkop, S Tunis
BACKGROUND: Gene therapy trial results show potential to cure haemophilia A and haemophilia B. Securing broad access to a cure for a lifelong chronic disease is anticipated to face barriers at the individual and healthcare system levels, which can be partly mitigated by harmonized planning of clinical research studies. The aim of the coreHEM project was to determine the set of outcome measures required to evaluate efficacy, safety, comparative effectiveness and value of gene therapy for haemophilia...
May 20, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29731970/elevated-seminal-plasma-estradiol-and-epigenetic-inactivation-of-esr1-and-esr2-is-associated-with-cp-cpps
#3
Nils Nesheim, Stuart Ellem, Temuujin Dansranjavin, Christina Hagenkötter, Elena Berg, Rupert Schambeck, Hans-Christian Schuppe, Adrian Pilatz, Gail Risbridger, Wolfgang Weidner, Florian Wagenlehner, Undraga Schagdarsurengin
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation)...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731636/critical-limb-ischemia-current-challenges-and-future-prospects
#4
REVIEW
Luigi Uccioli, Marco Meloni, Valentina Izzo, Laura Giurato, Stefano Merolla, Roberto Gandini
Critical limb ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. In this review, we presented a complete overview about physiopathology, diagnosis and holistic management of CLI. Revascularization is the first-line treatment, but several challenging cases are not treatable by conventional techniques...
2018: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/29661045/recent-approaches-for-targeted-drug-delivery-in-rheumatoid-arthritis-diagnosis-and-treatment
#5
Sana Pirmardvand Chegini, Jaleh Varshosaz, Somayeh Taymouri
Rheumatoid arthritis (RA) is a chronic inflammatory disease with complex pathology characterized by inflammation of joints, devastation of the synovium, pannus formation, bones and cartilage destruction and often is associated with persistent arthritic pain, swelling, stiffness and work disability. In conventional RA therapy, because of short biological half-life, poor bioavailability, high and frequent dosing is required. Thereby, these anti-RA medications, which unable to selectively target affected zone, may cause severe side effects in extra-articular tissues...
April 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29616344/novel-pharmacological-nonopioid-therapies-in-chronic-pain
#6
REVIEW
Alan David Kaye, Elyse M Cornett, Brendon Hart, Shilpadevi Patil, Andrew Pham, Matthew Spalitta, Kenneth F Mancuso
PURPOSE OF REVIEW: Opioid use and abuse has led to a worldwide opioid epidemic. And while opioids are clinically useful when appropriately indicated, they are associated with a wide range of dangerous side effects and whether they are effective at treating or eliminating chronic pain is controversial. There has long been a need for the development of nonopioid alternative treatments for patients that live in pain, and until recently, only a few effective treatments were available. Today, there are a wide range of nonopioid treatments available including NSAIDs, acetaminophen, corticosteroids, nerve blocks, SSRIs, neurostimulators, and anticonvulsants...
April 3, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29616222/does-a-better-perfusion-of-deconditioned-muscle-tissue-release-chronic-low-back-pain
#7
Paola Valdivieso, Martino V Franchi, Christian Gerber, Martin Flück
Non-specific chronic low back pain (nsCLBP) is a multifactorial condition of unknown etiology and pathogenesis. Physical and genetic factors may influence the predisposition of individuals to CLBP, which in many instances share a musculoskeletal origin. A reduced pain level in low back pain patients that participate in exercise therapy highlights that disuse-related muscle deconditioning may predispose individuals to nsCLBP. In this context, musculoskeletal pain may be the consequence of capillary rarefaction in inactive muscle as this would lower local tissue drainage and washing out of toxic waste...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29593249/inside-out-regenerative-medicine-for-recessive-dystrophic-epidermolysis-bullosa
#8
REVIEW
Michael Vanden Oever, Kirk Twaroski, Mark J Osborn, John E Wagner, Jakub Tolar
Epidermolysis bullosa is classified as a genodermatosis, an inherited genetic skin disorder that results in severe, chronic skin blistering with painful and life-threatening complications. Although there is currently no cure for epidermolysis bullosa, concurrent advances in gene and stem cell therapies are converging toward combinatorial therapies that hold the promise of clinically meaningful and lifelong improvement. Recent studies using hematopoietic stem cells and mesenchymal stromal/stem cells to treat epidermolysis bullosa have demonstrated the potential for sustained, effective management of the most severe cases...
January 2018: Pediatric Research
https://www.readbyqxmd.com/read/29532897/identification-of-the-key-genes-associated-with-neuropathic-pain
#9
Huan Liu, Tianjiao Xia, Fangxia Xu, Zhengliang Ma, Xiaoping Gu
Neuropathic pain is a chronic pain state associated with multiple etiologies that results in considerable social and economic burden. The identification of key genes associated with neuropathic pain is important for the development of novel therapies. Therefore, the present study downloaded the gene expression profile GSE15041 from the Gene Expression Omnibus database. The unverified gene chip was removed and the microarray data was normalized following quality control. The limma package in R was used to screen the differentially expressed genes (DEGs), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29463990/mesenchymal-stromal-stem-cell-derived-extracellular-vesicles-promote-human-cartilage-regeneration-in-vitro
#10
Lucienne A Vonk, Sanne F J van Dooremalen, Nalan Liv, Judith Klumperman, Paul J Coffer, Daniël B F Saris, Magdalena J Lorenowicz
Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair. METHODS: To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h...
2018: Theranostics
https://www.readbyqxmd.com/read/29406791/functional-abdominal-pain-disorders-in-children
#11
Shaman Rajindrajith, Judith Zeevenhooven, Niranga Manjuri Devanarayana, Bonaventure Jayasiri Crispus Perera, Marc A Benninga
Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on epidemiology, pathophysiology, risk factors related to pathophysiology, clinical evaluation and management of children with FAPDs. Expert commentary: FAPDs are a worldwide problem with a pooled prevalence of 13.5%. There are a number of predisposing factors and pathophysiological mechanisms including stressful events, child maltreatment, visceral hypersensitivity, altered gastrointestinal motility and change in intestinal microbiota...
April 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29406779/at-the-root-defining-and-halting-progression-of-early-chronic-obstructive-pulmonary-disease
#12
Fernando J Martinez, MeiLan K Han, James P Allinson, R Graham Barr, Richard C Boucher, Peter Calverley, Bartolome R Celli, Stephanie A Christenson, Ronald G Crystal, Malin Fagerås, Christine M Freeman, Lars Groenke, Eric A Hoffman, Mehmet Kesimer, Konstantinos Kostikas, Robert Paine Iii, Shahin Rafii, Stephen I Rennard, Leopoldo N Segal, Renat Shaykhiev, Christopher Stevenson, Ruth Tal-Singer, Jørgen Vestbo, Prescott G Woodruff, Jeffrey L Curtis, Jadwiga A Wedzicha
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with varying presentations and progression, but limited disease-modifying therapies. Trajectories of lung function decline in COPD differ significantly between individuals, with differences detectable in young adulthood. "Early disease" (initial manifestations in young individuals) should be distinguished from "late mild disease" (disease of mild severity in older individuals potentially present for decades). For research purposes, we propose an operational definition of early COPD: ever-smokers (≥10 pack-years) younger than 50 years with any of these abnormalities: (1) FEV1/FVC< lower limit of normal; (2) compatible CT abnormalities (airway abnormality and/or emphysema); or (3) FEV1 decline (≥60 mL/year)...
February 6, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29337163/utility-of-ultra-deep-sequencing-for-detection-of-varicella-zoster-virus-antiviral-resistance-mutations
#13
Mélanie Mercier-Darty, David Boutolleau, Raphaël Lepeule, Christophe Rodriguez, Sonia Burrel
We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant VZV infection initially detected by Sanger sequencing within a deeply immunocompromised heart transplant recipient. As added-value compared to Sanger analysis, UDS revealed complex dynamics of viral population under antiviral pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus affecting populations worldwide. VZV is commonly acquired in youth whose primary infection usually manifests as benign varicella (chickenpox)...
March 2018: Antiviral Research
https://www.readbyqxmd.com/read/29298725/sex-differences-in-primary-muscle-afferent-sensitization-following-ischemia-and-reperfusion-injury
#14
Jessica L Ross, Luis F Queme, Jordan E Lamb, Kathryn J Green, Michael P Jankowski
BACKGROUND: Chronic pain conditions are more prevalent in women, but most preclinical studies into mechanisms of pain generation are performed using male animals. Furthermore, whereas group III and IV nociceptive muscle afferents provoke central sensitization more effectively than their cutaneous counterparts, less is known about this critical population of muscle nociceptors. Here, we compare the physiology of individual muscle afferents in uninjured males and females. We then characterize the molecular, physiological, and behavioral effects of transient ischemia and reperfusion injury (I/R), a model we have extensively studied in males and in females...
January 3, 2018: Biology of Sex Differences
https://www.readbyqxmd.com/read/29276474/experimental-gene-therapy-with-serine-histogranin-and-endomorphin-1-for-the-treatment-of-chronic-neuropathic-pain
#15
Stanislava Jergova, Catherine E Gordon, Shyam Gajavelli, Jacqueline Sagen
The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29258584/lymphocyte-opioid-receptors-as-innovative-biomarkers-of-osteoarthritic-pain-for-the-assessment-and-risk-management-of-opioid-tailored-therapy-before-hip-surgery-to-prevent-chronic-pain-and-opioid-tolerance-addiction-development-opmarkart-opioids-markers-arthroprosthesis
#16
Valentina Malafoglia, Monica Celi, Carolina Muscoli, Sara Ilari, Filomena Lauro, Luigino Antonio Giancotti, Chiara Morabito, Maurizio Feola, Umberto Tarantino, William Raffaeli
BACKGROUND: The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction...
December 19, 2017: Trials
https://www.readbyqxmd.com/read/29248480/functional-therapies-for-cutaneous-wound-repair-in-epidermolysis-bullosa
#17
Patricia Peking, Ulrich Koller, Eva M Murauer
Chronic wounding as a result of recurrent skin blistering in the painful genetic skin disease epidermolysis bullosa, may lead to life-threatening infections, increased risk of tumor formation, and other serious medical complications. Therefore, epidermolysis bullosa patients have an urgent need for optimal wound care and tissue regeneration. Therapeutic strategies using gene-, protein-, and cell-therapies are being developed to improve clinical symptoms, and some of them have already been investigated in early clinical trials...
December 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29218074/autophagy-in-endometriosis
#18
REVIEW
Hui-Li Yang, Jie Mei, Kai-Kai Chang, Wen-Jie Zhou, Li-Qing Huang, Ming-Qing Li
Endometriosis (EMS) is a common gynecologic disease that causes chronic pelvic pain, dysmenorrhea, and infertility in women. The doctrine of menstruation back flow planting and defects in the immune system are well known and widely accepted. In recent years, increasing studies have been focused on the role of autophagy in EMS, and have shown that autophagy plays a vital role in EMS. Autophagy, which is known as the non-apoptotic form of programmed cell death induced by a large number of intracellular/extracellular stimuli, is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29183089/successful-treatment-of-estrogen-excess-in-primary-bilateral-macronodular-adrenocortical-hyperplasia-with-leuprolide-acetate
#19
Fady Hannah-Shmouni, Andreas G Moraitis, Vladimir Valera Romero, Fabio R Faucz, Spyridon A Mastroyannis, Annabel Berthon, Richard A Failor, Maria Merino, Andrew P Demidowich, Constantine A Stratakis
Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses...
February 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#20
Gunhyuk Park, Seung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal®) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor alpha (TNF-α) inhibitor to the treatment can be beneficial...
March 1, 2018: Journal of Ethnopharmacology
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