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Gene therapy pain

Vibeke Strand, Eun Bong Lee, Roy Fleischmann, Rieke E Alten, Tamas Koncz, Samuel H Zwillich, David Gruben, Bethanie Wilkinson, Sriram Krishnaswami, Gene Wallenstein
OBJECTIVES: To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. METHODS: In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36])...
2016: RMD Open
Aliye Uc, Dana K Andersen, Melena D Bellin, Jason I Bruce, Asbjørn M Drewes, John F Engelhardt, Christopher E Forsmark, Markus M Lerch, Mark E Lowe, Brent A Neuschwander-Tetri, Stephen J OʼKeefe, Tonya M Palermo, Pankaj Pasricha, Ashok K Saluja, Vikesh K Singh, Eva M Szigethy, David C Whitcomb, Dhiraj Yadav, Darwin L Conwell
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology, (2) exocrine complications, (3) endocrine complications, and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation...
November 2016: Pancreas
Cherry Yin-Yi Chang, Ming-Tsung Lai, Yi Chen, Ching-Wen Yang, Hui-Wen Chang, Cheng-Chan Lu, Chih-Mei Chen, Carmen Chan, Ching Chung, Chun-Cheng Tseng, Tritium Hwang, Jim Jinn-Chyuan Sheu, Fuu-Jen Tsai
Aberrant miRNA expression has been reported in endometriosis and miRNA gene polymorphisms have been linked to cancer. Because certain ovarian cancers arise from endometriosis, we genotyped seven cancer-related miRNA single nucleotide polymorphisms (MiRSNPs) to investigate their possible roles in endometriosis. Genetic variants in MIR196A2 (rs11614913) and MIR100 (rs1834306) were found to be associated with endometriosis development and related clinical phenotypes, such as infertility and pain. Downstream analysis of the MIR196A2 risk allele revealed upregulation of rRNA editing and protein synthesis genes, suggesting hyper-activation of ribosome biogenesis as a driving force for endometriosis progression...
September 15, 2016: Oncotarget
K V Firsov, A S Kotov
Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Manuel P Pereira, Sebastian Mühl, Esther M Pogatzki-Zahn, Konstantin Agelopoulos, Sonja Ständer
In recent years, measurement of the intraepidermal nerve fiber (IENF) density has gained relevance in the diagnostics of chronic pruritus. This method allows the objectification and quantification of a small-fiber neuropathy, which may manifest clinically with pruritus, pain or dysesthetic sensory symptoms, such as burning, stinging and tingling sensations or numbness. Upon suspicion of a small-fiber neuropathy as a cause for chronic pruritus, targeted diagnostic procedures are essential for the early detection of the neuroanatomical changes...
October 11, 2016: Dermatology and Therapy
Vanessa Lima Cavalcante de Oliveira, José Antonio Silva, Andrey Jorge Serra, Rodney Capp Pallotta, Evela Aparecida Pereira da Silva, Anna Cristina de Farias Marques, Regiane Dos Santos Feliciano, Rodrigo Labat Marcos, Ernesto Cesar Pinto Leal-Junior, Paulo de Tarso Camillo de Carvalho
The objective of this study was to evaluate the effects of photobiomodulation therapy (PBMT) on inflammatory indicators, i.e., inflammatory mediators (TNF-α and CINC-1), and pain characterized by hyperalgesia and B1 and B2 receptor activation at 6, 24, and 48 h after papain-induced osteoarthritis (OA) in rats. Fifty-four rats were subjected to hyperalgesia evaluations and then divided randomly into three groups-a control group and two groups OA and OA PBMT group by using laser parameters at wavelength (808 nm), output power (50 mW), energy per point (4 Joules), power density (1...
October 10, 2016: Lasers in Medical Science
Michael P Whyte, Katherine L Madson, Dawn Phillips, Amy L Reeves, William H McAlister, Amy Yakimoski, Karen E Mack, Kim Hamilton, Kori Kagan, Kenji P Fujita, David D Thompson, Scott Moseley, Tatjana Odrljin, Cheryl Rockman-Greenberg
Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s...
June 16, 2016: JCI Insight
C Kibaly, H H Loh, P-Y Law
Treatment of chronic pain has created a "silent epidemic," a term that describes the serious public health problem of the abuse of opioid painkillers and other prescription drugs. Conventional pharmacotherapy is limited by the loss of effectiveness in the long-term and by potentially lethal side effects. Efforts need to be focused on the development of nonpharmacological approaches. As significant progress is made in the viral vector technology, gene therapy involving recombinant viruses as vehicles may become a viable alternative for treatment of severe pain...
2016: International Review of Cell and Molecular Biology
Chia-Kai Liu, Wen-Tzu Liao, Yu-Chi Chu, Chien-Hui Yang, Kuan-Hung Chen, Chih-Hsien Wu, Chung-Ren Lin
BACKGROUND:  Pulsed radiofrequency (PRF) treatment offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA)-induced inflammatory pain. Epigenetic modification of potassium-chloride cotransporter 2 (KCC2) gene expression was examined to elucidate the potential contributing mechanism. METHODS:  Male Sprague-Dawley rats were injected with CFA into the plantar surface of the left hind paw to induce inflammation...
September 28, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Karin Pichler, Daniela Karall, Dieter Kotzot, Elisabeth Steichen-Gersdorf, Alexandra Rümmele-Waibel, Laureane Mittaz-Crettol, Julia Wanschitz, Luisa Bonafé, Kathrin Maurer, Andrea Superti-Furga, Sabine Scholl-Bürgi
Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a rare inherited progressive skeletal disorder caused by mutations in the matrix metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present successful bisphosphonate therapy in three affected patients. Patients were treated with bisphosphonates (either pamidronate or zoledronate) for different time periods. The following outcome variables were assessed: skeletal pain, range of motion, bone densitometry, internal medical problems as well as neurocognitive function...
September 30, 2016: Scientific Reports
Simon Wan, Samantha Borland, Stephen M Richardson, Catherine L R Merry, Alberto Saiani, Julie E Gough
: Cell-based therapies for regeneration of intervertebral discs are regarded to hold promise for degenerative disc disease treatment, a condition that is strongly linked to lower back pain. A de novo self-assembling peptide hydrogel (SAPH), chosen for its biocompatibility, tailorable properties and nanofibrous architecture, was investigated as a cell carrier and scaffold for nucleus pulposus (NP) tissue engineering. Oscillatory rheology determined that the system would likely be deliverable via minimally invasive procedure and mechanical properties could be optimised to match the stiffness of the native human NP...
September 24, 2016: Acta Biomaterialia
Ana M Peiró, Beatriz Planelles, Gabriella Juhasz, György Bagdy, Frédéric Libert, Alain Eschalier, Jérôme Busserolles, Beata Sperlagh, Adrián Llerena
The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter-individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics...
September 1, 2016: Drug Metabolism and Personalized Therapy
Adrienne E Borrie, Richard B Kim
INTRODUCTION: Aromatase inhibitors (AIs) are routinely used for the adjuvant treatment of women with hormone receptor-positive early breast cancer. AIs are widely prescribed in the postmenopausal setting, as they are effective at preventing recurrence. However, their use is complicated by significant adverse effects, particularly arthralgia, noted in up to 50% of treated patients, and thereby affects quality of life and AI compliance. The mechanism by which AIs cause arthralgia is largely unknown, although there is a growing body of literature which suggests that there may be multiple intersecting mechanisms...
September 16, 2016: Expert Opinion on Drug Metabolism & Toxicology
C Gils, M-C Eckhardt, P E Nielsen, M Nybo
Background. Congenital chloride diarrhea (CCD) is an autosomal recessive disorder caused by mutations in the genes encoding the intestinal Cl(-)/HCO3 (-) exchanger and is clinically characterized by watery, profound diarrhea, electrolyte disturbances, and metabolic alkalosis. The CCD diagnosis is based on the clinical symptoms and measurement of high chloride concentration in feces (>90 mmol/L) and is confirmed by DNA testing. Untreated CCD is lethal, while long-term clinical outcome improves when treated correctly...
2016: Case Reports in Pediatrics
Nirali N Shah, David M Loeb, Hahn Khuu, David Stroncek, Tolu Ariyo, Mark Raffeld, Cindy Delbrook, Crystal L Mackall, Alan S Wayne, Terry J Fry
Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues...
September 12, 2016: Biology of Blood and Marrow Transplantation
Li-Na Dai, Ying-Wei Chen, Wei-Hui Yan, Li-Na Lu, Yi-Jing Tao, Wei Cai
BACKGROUND: Hereditary pancreatitis (HP) is quite rare and is distinguished by incomplete penetrance presentation as early-onset relapsing pancreatitis, usually beginning in childhood. HP is now known to be commonly relevant to mutations in the PRSS1 (gene-encoding cationic trypsinogen), SPINK1 (serine protease inhibitor, Kazal type 1), CFTR (cystic fibrosis), carboxypeptidase A1 (CPA1), and chymotrypsin C (CTRC) genes as reported in some Caucasian studies. HP has a variable spectrum of severity and may develop complications...
September 2016: Medicine (Baltimore)
Shirley P Yu, David J Hunter
INTRODUCTION: Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. AREAS COVERED: Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy...
October 2016: Expert Opinion on Pharmacotherapy
Yee-Chin Wong, Moataz Abd El Ghany, Raeece Naeem, Kok-Wei Lee, Yung-Chie Tan, Arnab Pain, Sheila Nathan
Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing) as a genome-wide screening tool to facilitate the identification of B...
2016: Frontiers in Microbiology
Mónica Furlano, Yaima Barreiro, Teresa Martí, Carme Facundo, César Ruiz-García, Iara DaSilva, Nadia Ayasreh, Cristina Cabrera-López, José Ballarín, Elisabet Ars, Roser Torra
We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis (TS) and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML), which are common benign tumours in patients with TS. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding...
August 29, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Chunsheng Hu, Zhenzhen Cai, Yuxin Lu, Xiaochen Cheng, Zuze Wu, Qinglin Zhang
We investigated the antinociceptive effect of local intramuscular injection of a plasmid encoding human proenkephalin (pVAX1-hPPE) on postoperative pain in rats. Male Sprague-Dawley rats with incision-induced pain were intramuscularly injected into injured plantaris muscle with empty vector (pVAX1) or pVAX1-hPPE, respectively. Paw mechanical threshold and thermal latency in the 200μg pVAX1-hPPE treated rats were significantly higher at 6h and on 1day, and lasted until day 7 after intramuscular administration, respectively...
October 6, 2016: Neuroscience Letters
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