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Gene therapy pain

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https://www.readbyqxmd.com/read/29781145/core-outcome-set-for-gene-therapy-in-haemophilia-results-of-the-corehem-multistakeholder-project
#1
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/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#2
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29763613/neuroprotective-effect-of-duloxetine-in-a-mouse-model-of-diabetic-neuropathy-role-of-glia-suppressing-mechanisms
#3
Mona K Tawfik, Seham A Helmy, Dahlia I Badran, Sawsan A Zaitone
AIMS: Painful diabetic neuropathy (PDN) is one of the most frequent complications of diabetes and the current therapies have limited efficacy. This study aimed to study the neuroprotective effect of duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), in a mouse model of diabetic neuropathy. MAIN METHODS: Nine weeks after developing of PDN, mice were treated with either saline or duloxetine (15 or 30 mg/kg) for four weeks. The effect of duloxetine was assessed in terms of pain responses, histopathology of sciatic nerve and spinal cord, sciatic nerve growth factor (NGF) gene expression and on the spinal expression of astrocytes (glial fibrillary acidic protein, GFAP) and microglia (CD11 b)...
May 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29750992/transcriptome-analysis-of-dorsal-root-ganglia-s-diabetic-neuropathy-reveals-mechanisms-involved-in-pain-and-regeneration
#4
Maria Carolina Pedro Athie, Andre Schwambach Vieira, Juliana Maia Teixeira, Gilson Gonçalves Dos Santos, Elayne Vieira Dias, Claudia Herrera Tambeli, Cesar Renato Sartori, Carlos A Parada
Peripheral diabetic neuropathy (DN) manifests in nearly 60% of diabetic patients, being pain its most debilitating symptom. Although electrophysiological and morphological aspects are well described, little is known about its development and progression, undermining effective therapies. Hyperglycemia and insulin signaling impairment are considered the triggering events of oxidative stress observed in the dying nerves, however there are still many gaps in the knowledge of intracellular plastic changes it generates...
May 8, 2018: Life Sciences
https://www.readbyqxmd.com/read/29745371/microrna-194-inhibits-lipopolysaccharide-induced-inflammatory-response-in-nucleus-pulposus-cells-of-the-intervertebral-disc-by-targeting-tnf-receptor-associated-factor-6-traf6
#5
Lili Kong, Mingxiao Sun, Zhaofu Jiang, Liming Li, Bing Lu
BACKGROUND The dramatic increase of intervertebral disc degeneration (IDD) is considered to be a major cause of discogenic low back pain. The current study focused on the regulatory function of microRNA-194 (miR-194) on lipopolysaccharide (LPS)-induced inflammatory response in nucleus pulposus (NP) cells. MATERIAL AND METHODS LPS was used to treat NP cells to induce inflammatory responses. MiRNA and gene expression were detected by quantitative PCR. Proteins and protein expression levels were detected by Western blot and ELISA kit...
May 10, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29739272/notochordal-cell-matrix-as-a-therapeutic-agent-for-intervertebral-disc-regeneration
#6
Stefan de Vries, Marina van Doeselaar, Björn Meij, Marianna A Tryfonidou, Keita Ito
Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2...
May 9, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29731970/elevated-seminal-plasma-estradiol-and-epigenetic-inactivation-of-esr1-and-esr2-is-associated-with-cp-cpps
#7
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
#8
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/29691490/cgrp-as-the-target-of-new-migraine-therapies-successful-translation-from-bench-to-clinic
#9
REVIEW
Lars Edvinsson, Kristian Agmund Haanes, Karin Warfvinge, Diana N Krause
Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects...
April 24, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29690597/liu-jun-zi-tang-a-potential-multi-herbal-complementary-therapy-for-chemotherapy-induced-neurotoxicity
#10
Chun-Tang Chiou, Kaw-Chen Wang, Ying-Chen Yang, Chuen-Lin Huang, Sien-Hung Yang, Yao-Haur Kuo, Nai-Kuei Huang
Liu Jun Zi Tang (LJZT) has been used to treat functional dyspepsia and depression, suggesting its effects on gastrointestinal and neurological functions. LJZT is currently used as a complementary therapy to attenuate cisplatin-induced side effects, such as dyspepsia. However, its effect on chemotherapy-induced neuropathic pain or neurotoxicity has rarely been studied. Thus, we explored potential mechanisms underlying LJZT protection against cisplatin-induced neurotoxicity. We observed that LJZT attenuated cisplatin-induced thermal hyperalgesia in mice and apoptosis in human neuroblastoma SH-SY5Y cells...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29681086/a-novel-homozygous-mutation-in-the-slco2a1-gene-causing-pachydermoperiostosis-efficacy-of-hydroxychloroquine-treatment
#11
Annalisa Alessandrella, Roberto Della Casa, Maria Alessio, Jorge Puente Prieto, Pietro Strisciuglio, Daniela Melis
Pachydermoperiostosis (PDP), otherwise known as primary hypertrophic osteoarthropathy, is characterized by digital clubbing, pachydermia and subperiosteal new bone formation. Joint pain, polyarthritis, cutis verticis gyrata, seborrhea, and hyperhidrosis are frequently associated to this condition. We report a 17-year-old boy presented with pain and swelling of knees and ankles, and progressive thickening of skin face with seborrhea from about 4 years. At the admission he also showed digital clubbing of both hands and feet and palmoplantar hyperhidrosis...
May 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29661045/recent-approaches-for-targeted-drug-delivery-in-rheumatoid-arthritis-diagnosis-and-treatment
#12
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/29625594/the-first-case-of-smarcb1-ini1-deficient-squamous-cell-carcinoma-of-the-pleura-a-case-report
#13
Kazushi Yoshida, Yutaka Fujiwara, Yasushi Goto, Takashi Kohno, Akihiko Yoshida, Koji Tsuta, Yuichiro Ohe
BACKGROUND: SMARCB1 (INI1) is a tumor-suppressor gene located at 22q11.2. Loss of SMARCB1 protein expression has been reported to be associated with atypical teratoid/rhabdoid tumors and malignant rhabdoid tumors of the kidney and extrarenal tissues. To date, however, SMARCB1-deficient carcinoma of the pleura has not been reported. We report the first case of SMARCB1- deficient squamous cell carcinoma of the pleura. CASE PRESENTATION: The case was a 33-year-old female...
April 7, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29622035/ccl17-blockade-as-a-therapy-for-osteoarthritis-pain-and-disease
#14
Ming-Chin Lee, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Irmgard Förster, John A Hamilton, Andrew D Cook
BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We identified previously a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can also be linked with this pathway. Here we investigated the involvement of the pathway in OA pain and disease development using the GM-CSF-dependent collagenase-induced OA (CiOA) model...
April 5, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29620655/clinical-characteristics-and-treatment-outcomes-in-camurati-engelmann-disease-a-case-series
#15
Yoon-Myung Kim, Eungu Kang, Jin-Ho Choi, Gu-Hwan Kim, Han-Wook Yoo, Beom Hee Lee
BACKGROUND: Camurati-Engelmann disease is an extremely rare disease characterized by hyperostosis of multiple long bones. This condition is caused by heterozygous mutations in the TGFB1 gene. METHODS: We describe the clinical and genetic characteristics of 4 Korean patients with this rare disease diagnosed at Asan Medical Center in Korea between June 2012 and May 2016, to increase awareness about this condition among general physicians and orthopedists. The presenting features, biochemical findings, radiographic and nuclear imaging findings, molecular analysis, and treatment outcomes of 4 patients were reviewed retrospectively...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29620650/durable-remission-in-a-patient-of-mixed-phenotype-acute-leukemia-with-philadelphia-chromosome-positive-treated-with-nilotinib-and-lenalidomide-a-case-report
#16
Binbin Lai, Qitian Mu, Huiling Zhu, Yi Wang, Yi Zhang, Kaihong Xu, Lixia Sheng, Guifang Ouyang
RATIONALE: Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph+ MPAL) is a rare type of leukemia with poor prognosis. Tyrosine kinase inhibitors (TKIs) in combination with chemotherapy have significantly improved its remission rate. However, relapse remains the major obstacle to achieve long survival. Lenalidomide is a second-generation oral immunomodulatory drug that has been broadly applied in the treatment of various hematological malignancies. PATIENT CONCERNS: A 54-year-old Chinese male patient who complained of chest pain and fatigue for 20 days...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29618309/genetics-and-gene-therapy-of-anderson-fabry-disease
#17
Irene Simonetta, Antonino Tuttolomondo, Tiziana Di Chiara, Salvatore Miceli
Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by demonstration of absence or reduced alpha galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay alone in women is inconclusive...
April 4, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29616830/cgrp-a-target-for-acute-therapy-in-migraine-clinical-data
#18
Roberta Messina, Peter J Goadsby
Background A better understanding of the mechanisms underlying the migraine attack has reinforced the concept that migraine is a complex brain disease, and has paved the way for the development of new migraine specific acute treatments. In recent years, targeting the calcitonin gene-related peptide and its receptors has been one of the most promising pharmacological strategies for both acute and preventive treatment of migraine. Findings Randomized double-blind placebo-controlled trials have demonstrated the superiority of small molecule calcitonin gene-related peptide receptor antagonists (gepants) over placebo in treating acute migraine attacks measured as the two-hour pain free endpoint...
January 1, 2018: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29616344/novel-pharmacological-nonopioid-therapies-in-chronic-pain
#19
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
#20
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
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