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Gene therapy chronic pain

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https://www.readbyqxmd.com/read/29337163/utility-of-ultra-deep-sequencing-for-detection-of-varicella-zoster-virus-antiviral-resistance-mutations
#1
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)...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29298725/sex-differences-in-primary-muscle-afferent-sensitization-following-ischemia-and-reperfusion-injury
#2
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
#3
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
#4
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
#5
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 14, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29218074/autophagy-in-endometriosis
#6
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
#7
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...
November 28, 2017: 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
#8
Gunhyuk Park, Seoung 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 auto-immune 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 (TNF)-α inhibitor to the treatment can be beneficial...
November 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29150266/interleukin-35-and-hepatocyte-growth-factor-as-a-novel-combined-immune-gene-therapy-for-multiple-sclerosis-disease
#9
Samira Moghadam, Maryam Erfanmanesh, Abdolreza Esmaeilzadeh
An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29130055/gene-therapy-with-hsv-encoding-p55tnfr-gene-for-hiv-neuropathic-pain-an-evidence-based-mini-review
#10
Hirotsugu Kanda, Shue Liu, Megumi Kanao, Hyun Yi, Takafumi Iida, Wan Huang, Takayuki Kunisawa, David A Lubarsky, Shuanglin Hao
While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain...
2017: Translational Perioperative and Pain Medicine
https://www.readbyqxmd.com/read/29113923/effects-of-spinal-non-viral-interleukin-10-gene-therapy-formulated-with-d-mannose-in-neuropathic-interleukin-10-deficient-mice-behavioral-characterization-mrna-and-protein-analysis-in-pain-relevant-tissues
#11
Arden G Vanderwall, Shahani Noor, Melody S Sun, Jacob E Sanchez, Xuexian O Yang, Lauren L Jantzie, Nikolaos Mellios, Erin D Milligan
Studies show that spinal (intrathecal; i.t.) interleukin-10 (IL-10) gene therapy reverses neuropathic pain in animal models, and co-administration with the mannose receptor (MR; CD206) ligand d-mannose (DM) greatly improves therapeutic efficacy. However, the actions of endogenous IL-10 may be required for enduring pain control observed following i.t. IL-10 gene therapy, potentially narrowing the application of this non-viral transgene delivery approach. Here, we show that i.t. application of naked plasmid DNA expressing the IL-10 transgene co-injected with DM (DM/pDNA-IL-10) for the treatment of peripheral neuropathic pain in IL-10 deficient (IL-10 KO) mice results in a profound and prolonged bilateral pain suppression...
November 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29093260/-a-case-of-gitelman-syndrome-with-physical-retardation
#12
Juan Huang, Xiangrong Zheng, Dandan Guo, Guoyuan Zhang, Xia Wang, Chentao Liu
Gitelman syndrome is a rare disease. It is easy to be misdiagnosed and missed diagnosis due to the diverse clinical symptoms. A girl with long-term hypokalemia, who presented with intermittent pain of lower limb muscle and physical retardation, was treated in Xiangya Hospital, Central South University. Laboratory examination confirmed the severe hypokalemia and metabolic alkalosis. Gene sequencing indicated SLC12A3 gene mutation and the patient was finally diagnosed as Gitelman syndrome. Patients with chronic hypokalemia and metabolic alkalosis need to conduct gene sequencing to confirm the diagnosis...
October 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29084074/clinical-and-symptom-scores-are-significantly-correlated-with-fecal-microbiota-features-in-patients-with-symptomatic-uncomplicated-diverticular-disease-a-pilot-study
#13
Charlotte L Kvasnovsky, Lex E X Leong, Jocelyn M Choo, Guy C J Abell, Savvas Papagrigoriadis, Kenneth D Bruce, Geraint B Rogers
BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis. OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis. PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing...
October 27, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29075135/dnmt3a-methylation-in-neuropathic-pain
#14
Cuijie Shao, Yong Gao, Dan Jin, Xin Xu, Shuying Tan, Hui Yu, Qingxiang Zhao, Li Zhao, Wansheng Wang, Deqiang Wang
BACKGROUND: Mu opioid receptor (MOR) plays a crucial role in mediating analgesic effects of opioids and is closely associated with the pathologies of neuropathic pain. Previous studies have reported that peripheral nerve injury downregulates MOR expression, but the epigenetic mechanisms remain unknown. OBJECTIVE: Therefore, we investigated DNA methyltransferase3a (DNMT3a) expression or methylation changes within MOR promoter in the spinal cord in a neuropathic pain induced by a chronic constriction injury (CCI) mouse model and further determined whether these injury-associated changes are reversible by pharmacological interventions...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29057994/effects-of-herpes-simplex-virus-vectors-encoding-poreless-trpv1-or-protein-phosphatase-1%C3%AE-in-a-rat-cystitis-model-induced-by-hydrogen-peroxide
#15
S Takai, T Majima, B Reinhart, W F Goins, Y Funahashi, M Gotoh, P Tyagi, J C Glorioso, N Yoshimura
Enhanced afferent excitability is considered to be an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS). In addition, transient receptor potential vanilloid-1 (TRPV1) receptors are known to be involved in afferent sensitization. Animals with hydrogen peroxide (HP)-induced cystitis have been used as a model exhibiting pathologic characteristics of chronic inflammatory condition of the bladder. This study investigated the effect of gene therapy with replication-defective herpes simplex virus (HSV) vectors encoding poreless TRPV1 (PL) or protein phosphatase 1 α (PP1α), a negative regulator of TRPV1, using a HP-induced rat model of cystitis...
October 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29046485/dimethyl-fumarate-increases-fetal-hemoglobin-provides-heme-detoxification-and-corrects-anemia-in-sickle-cell-disease
#16
Sriram Krishnamoorthy, Betty Pace, Dipti Gupta, Sarah Sturtevant, Biaoru Li, Levi Makala, Julia Brittain, Nancy Moore, Benjamin F Vieira, Timothy Thullen, Ivan Stone, Huo Li, William E Hobbs, David R Light
Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)-like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell-derived erythroid progenitors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29032938/the-jak-stat-signaling-pathway-and-photobiomodulation-in-chronic-wound-healing
#17
Sandy W Jere, Heidi Abrahamse, Nicolette N Houreld
Wound healing is a physiological process that occurs in overlapping phases namely hemostasis, inflammation, proliferation, and remodeling. Chronic wounds fail to proceed through these reparative processes to achieve the functional integrity within the expected time. Wound healing relies upon growth factors and cytokines for the precise and accurate regulation of cellular responses. These are achieved through the use of complex growth factor/cytokine induced signaling pathways. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transmits extracellular signals to the nucleus for the transcription of genes involved in proliferation and differentiation, to name but a few...
October 6, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#18
Manel Ben Aissa, Alycia F Tipton, Zachariah Bertels, Ronak Gandhi, Laura S Moye, Madeline Novack, Brian M Bennett, Yueting Wang, Vladislav Litosh, Sue H Lee, Irina N Gaisina, Gregory Rj Thatcher, Amynah A Pradhan
Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29021995/tumor-induced-osteomalacia
#19
Pablo Florenzano, Rachel I Gafni, Michael T Collins
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23) that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/28967365/hypermobility-the-ehlers-danlos-syndromes-and-chronic-pain
#20
REVIEW
Delfien Syx, Inge De Wandele, Lies Rombaut, Fransiska Malfait
Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes...
September 2017: Clinical and Experimental Rheumatology
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