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https://www.readbyqxmd.com/read/28716575/strategic-targeting-of-multiple-bmp-receptors-prevents-trauma-induced-heterotopic-ossification
#1
Shailesh Agarwal, Shawn J Loder, Christopher Breuler, John Li, David Cholok, Cameron Brownley, Jonathan Peterson, Hsiao H Hsieh, James Drake, Kavitha Ranganathan, Yashar S Niknafs, Wenzhong Xiao, Shuli Li, Ravindra Kumar, Ronald Tompkins, Michael T Longaker, Thomas A Davis, Paul B Yu, Yuji Mishina, Benjamin Levi
Trauma-induced heterotopic ossification (tHO) is a condition of pathologic wound healing, defined by the progressive formation of ectopic bone in soft tissue following severe burns or trauma. Because previous studies have shown that genetic variants of HO, such as fibrodysplasia ossificans progressiva (FOP), are caused by hyperactivating mutations of the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO have been directed primarily toward drugs for this specific receptor...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28643056/deep-neuromuscular-blockade-improves-surgical-conditions-during-low-pressure-pneumoperitoneum-laparoscopic-donor-nephrectomy
#2
D M D Özdemir-van Brunschot, A E Braat, M F P van der Jagt, G J Scheffer, C H Martini, J F Langenhuijsen, R E Dam, V A Huurman, D Lam, F C d'Ancona, A Dahan, M C Warlé
BACKGROUND: Evidence indicates that low-pressure pneumoperitoneum (PNP) reduces postoperative pain and analgesic consumption. A lower insufflation pressure may hamper visibility and working space. The aim of the study is to investigate whether deep neuromuscular blockade (NMB) improves surgical conditions during low-pressure PNP. METHODS: This study was a blinded randomized controlled multicenter trial. 34 kidney donors scheduled for laparoscopic donor nephrectomy randomly received low-pressure PNP (6 mmHg) with either deep (PTC 1-5) or moderate NMB (TOF 0-1)...
June 22, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28611046/autocrine-bmp-4-signaling-is-a-therapeutic-target-in-colorectal-cancer
#3
Yuichiro Yokoyama, Toshiaki Watanabe, Yusuke Tamura, Yoshinobu Hashizume, Kohei Miyazono, Shogo Ehata
Poor prognoses for colorectal cancer (CRC) patients with metastatic lesions have driven demand for the development of novel targeted therapies. Here we demonstrate that expression of bone morphogenetic protein 4 (BMP-4) is universally upregulated in human CRC cells and tissues, resulting in activated BMP signaling. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 elevated expression of the phosphatase DUSP5 in CRC cells, inducing apoptosis via dephosphorylation of Erk MAPK...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608013/quality-of-recovery-after-low-pressure-laparoscopic-donor-nephrectomy-facilitated-by-deep-neuromuscular-blockade-a-randomized-controlled-study
#4
Denise M D Özdemir-van Brunschot, Gert J Scheffer, Michel van der Jagt, Hans Langenhuijsen, Albert Dahan, Janneke E E A Mulder, Simone Willems, Luuk B Hilbrands, Rogier Donders, Cees J H M van Laarhoven, Frank A d'Ancona, Michiel C Warlé
BACKGROUND: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. OBJECTIVE: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). DESIGN, SETTING AND PARTICIPANTS: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure...
June 12, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28607287/does-carbon-dioxide-pneumoperitoneum-affect-the-renal-function-in-donors-following-laparoscopic-donor-nephrectomy-a-prospective-study
#5
Murali Vinodh, Vijaykumar Mohankumar, Arvind Ganpule, Banibrata Mukhopadhyay, Ravindra Sabnis, Mahesh Desai
CONTEXT: Although the technical feasibility of laparoscopic donor nephrectomy (LDN) has been established, concerns have been raised about the impaired renal function resulting from pneumoperitoneum and its short- and long-term effects. AIMS: We used urinary biomarkers of acute kidney injury including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary N-acetyl-beta-D-glucosaminidase (uNAG) to study the injury caused to the donor's retained kidney by pneumoperitoneum...
July 2017: Journal of Minimal Access Surgery
https://www.readbyqxmd.com/read/28591959/-learning-curve-of-retroperitoneal-laparoscopic-donor-nephrectomy-and-risk-analysis-of-intraoperative-complications
#6
Yang Qiu, Tu-Run Song, Zheng-Sheng Rao, Xian-Ding Wang, Zhong-Li Huang, Tao Lin
OBJECTIVES: To investigate the learning curve of retroperitoneal laparoscopic donor nephrectomy (LDN) and evaluate the risk factors of intraoperative complications with data from a single center. METHODS: We evaluated perioperative data of 527 consecutive kidney donors who received retroperitoneal LDN between April 2009 and April 2014. The patients were divided into two groups according to the learning curve which was determined by the operation time:group 1 (on the learning curve) and group 2 (learning curve completed)...
July 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28570212/vascular-control-during-laparoscopic-kidney-donation
#7
Thomas B McGregor, Premal Patel, Alp Sener, Gabriel Chan
Laparoscopic donor nephrectomy (LDN) is the gold standard for kidney donation. Recent literature has led to considerable debate regarding the safest route to provide vascular control during this procedure. The most common devices used for vascular control during LDN are staplers and surgical clips. Opinions regarding the safety of these devices vary, as both are prone to dysfunction. Certain clips have already been contraindicated for use on the donor artery owing to reports of catastrophic complications of falling off...
June 2017: Canadian Journal of Surgery. Journal Canadien de Chirurgie
https://www.readbyqxmd.com/read/28569204/tgf%C3%AE-1-induced-smad2-3-and-smad1-5-phosphorylation-are-both-alk5-kinase-dependent-in-primary-chondrocytes-and-mediated-by-tak1-kinase-activity
#8
Arjan van Caam, Wojciech Madej, Amaya Garcia de Vinuesa, Marie-José Goumans, Peter Ten Dijke, Esmeralda Blaney Davidson, Peter van der Kraan
BACKGROUND: Dysregulated transforming growth factor β (TGFβ) signaling is implicated in osteoarthritis development, making normalizing TGFβ signaling a possible therapy. Theoretically, this can be achieved with small molecule inhibitors specifically targeting the various TGFβ receptors and downstream mediators. In this study we explore in primary chondrocytes the use of small molecule inhibitors to target TGFβ-induced pSmad1/5/9-, pSmad2/3- and TGFβ-activated kinase 1 (TAK1)-dependent signaling...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28558263/the-role-of-traffic-noise-on-the-association-between-air-pollution-and-children-s-lung-function
#9
Meredith Franklin, Scott Fruin
Although it has been shown that traffic-related air pollution adversely affects children's lung function, few studies have examined the influence of traffic noise on this association, despite both sharing a common source. Estimates of noise exposure (Ldn, dB), and freeway and non-freeway emission concentrations of oxides of nitrogen (NOx, ppb) were spatially assigned to children in Southern California who were tested for forced vital capacity (FVC, n=1345), forced expiratory volume in 1s, (FEV1, n=1332), and asthma...
August 2017: Environmental Research
https://www.readbyqxmd.com/read/28549538/processing-of-word-stress-related-acoustic-information-a-multi-feature-mmn-study
#10
Ferenc Honbolygó, Orsolya Kolozsvári, Valéria Csépe
In the present study, we investigated the processing of word stress related acoustic features in a word context. In a passive oddball multi-feature MMN experiment, we presented a disyllabic pseudo-word with two acoustically similar syllables as standard stimulus, and five contrasting deviants that differed from the standard in that they were either stressed on the first syllable or contained a vowel change. Stress was realized by an increase of f0, intensity, vowel duration or consonant duration. The vowel change was used to investigate if phonemic and prosodic changes elicit different MMN components...
May 23, 2017: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/28536359/reduced-pro-inflammatory-cytokines-after-eight-weeks-of-low-dose-naltrexone-for-fibromyalgia
#11
Luke Parkitny, Jarred Younger
Fibromyalgia (FM) is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN). We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF)...
April 18, 2017: Biomedicines
https://www.readbyqxmd.com/read/28525717/synthesis-and-biological-evaluation-of-novel-neuroprotective-pyridazine-derivatives-as-excitatory-amino-acid-transporter-2-eaat2-activators
#12
Alessia Chelini, Simone Brogi, Marco Paolino, Angela Di Capua, Andrea Cappelli, Gianluca Giorgi, Mersedeh Farzad, Lorenzo Di Cesare Mannelli, Laura Micheli, Carla Ghelardini, Maurizio Anzini
LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the normal clearance of glutamate and providing neuronal protection. Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropathic pain, we synthesized novel activators (4a-f) of EAAT2. Among them 4f, analyzed in comparison with 3 by different paradigms in a rat model of oxaliplatin-induced neuropathic pain, showed the better antihypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy...
May 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28504556/evolution-of-technique-in-laparoscopic-donor-nephrectomy-a-single-center-experience
#13
Davide Cintorino, Duilio Pagano, Pasquale Bonsignore, Fabrizio di Francesco, Sergio Li Petri, Calogero Ricotta, Salvatore Gruttadauria
BACKGROUND: Renal transplantation is the most successful therapy for improving survival and quality of life for end-stage renal disease (ESRD). Living donor kidney transplantation (LDKTx) has been used as an alternative to reduce the stay on the waiting list of patients with ESRD. Laparoscopic donor nephrectomy (LDN) has become the standard procedure for LDKTx. OBJECTIVE: This study aims to describe evolution of surgical technique with LDN at our institute. MATERIALS AND METHODS: We retrospectively analyzed our experience with LDN performed from January, 2003 to November, 2016, focusing on describing modifications of the surgical technique and devices made during those years...
July 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/28458020/signaling-by-growth-differentiation-factor-5-through-the-bone-morphogenetic-protein-receptor-type-ib-protects-neurons-against-kainic-acid-induced-neurodegeneration
#14
Yuanzheng Zhao, Min Zhang, Hengfang Liu, Jianping Wang
Growth/differentiation factor-5 (GDF-5), a member of the transforming growth factor-beta (TGF-β) superfamily, has been shown to protect rat dopaminergic neurons against insult both in embryonic neuronal culture and in Parkinson's disease models. However, whether GDF-5 exerts neuroprotective effects in hippocampal neurons is unclear. Here, we show that both mRNA levels and protein levels of GDF-5 are decreased in the mouse hippocampus upon kainic acid (KA) treatment. KA induced dramatic neuronal loss specifically in the cornu ammonis 1 (CA1) and CA3 areas of the mouse hippocampus, while intracerebral infusion of GDF-5 prevented this neuronal loss...
April 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28445472/unsuspected-osteochondroma-like-outgrowths-in-the-cranial-base-of-hereditary-multiple-exostoses-patients-and-modeling-and-treatment-with-a-bmp-antagonist-in-mice
#15
Sayantani Sinha, Christina Mundy, Till Bechtold, Federica Sgariglia, Mazen M Ibrahim, Paul C Billings, Kristen Carroll, Eiki Koyama, Kevin B Jones, Maurizio Pacifici
Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths-called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28419135/an-organotypic-slice-culture-to-study-the-formation-of-calyx-of-held-synapses-in-vitro
#16
Elin Kronander, Nicolas Michalski, Cécile Lebrand, Jean-Pierre Hornung, Ralf Schneggenburger
The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zones, is possibly the largest nerve terminal in the mammalian CNS. Studying its initial growth in-vitro might provide insights into the specification of synaptic connection size in the developing brain. However, attempts to maintain calyces of Held in organotypic cultures have not been fruitful in past studies. Here, we describe an organotypic slice culture method in which calyces of Held form in-vitro. We made coronal brainstem slices with an optimized slice angle using newborn mice in which calyces have not yet formed; the presynaptic bushy cells were genetically labeled using the Math5 promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28410920/potential-drug-interaction-with-opioid-agonist-in-the-setting-of-chronic-low-dose-opioid-antagonist-use
#17
James B Leonard, Vidya Nair, Christopher J Diaz, Jonathan B Penoyar, Penelope A Goode
Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis...
April 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28393916/production-and-glyco-engineering-of-immunomodulatory-helminth-glycoproteins-in-plants
#18
Ruud H P Wilbers, Lotte B Westerhof, Kim van Noort, Katja Obieglo, Nicole N Driessen, Bart Everts, Sonja I Gringhuis, Gabriele Schramm, Aska Goverse, Geert Smant, Jaap Bakker, Hermelijn H Smits, Maria Yazdanbakhsh, Arjen Schots, Cornelis H Hokke
Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminth-derived glycoproteins for the treatment of immune-related diseases, like allergies and autoimmune diseases. Studies are however hampered by the limited availability of native parasite-derived proteins. Moreover, recombinant protein production systems have thus far been unable to reconstitute helminth-like glycosylation essential for the functionality of some helminth glycoproteins...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28390716/management-practices-physically-effective-fiber-and-ether-extract-are-related-to-bulk-tank-milk-de-novo-fatty-acid-concentration-on-holstein-dairy-farms
#19
M E Woolpert, H M Dann, K W Cotanch, C Melilli, L E Chase, R J Grant, D M Barbano
The objective of this study was to evaluate the relationship of management practices and dietary factors with de novo fatty acid concentration in bulk tank milk from commercial dairy farms milking Holstein cows. Farms were selected based on de novo fatty acid concentration during the 6 mo before the farm visit and were categorized as high de novo (HDN; 24.61 ± 0.75 g/100 g of fatty acids, mean ± standard deviation; n = 19) or low de novo (LDN; 23.10 ± 0.88 g/100 g of fatty acids; n = 20). Farms were visited once in February, March, or April 2015 and evaluated based on management and facility design known to affect cow behavior, physical and chemical characteristics of the diet, and ration formulation and forage analyses obtained from the farm's nutritionist...
April 5, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28370746/low-dose-naltrexone-and-opioid-consumption-a-drug-utilization-cohort-study-based-on-data-from-the-norwegian-prescription-database
#20
Guttorm Raknes, Lars Småbrekke
PURPOSE: Low-dose naltrexone (LDN) is used in a wide range of conditions, including chronic pain and fibromyalgia. Because of the opioid antagonism of naltrexone, LDN users are probably often warned against concomitant use with opioids. In this study, based on data from the Norwegian prescription database, we examine changes in opioid consumption after starting LDN therapy. METHODS: We included all Norwegian patients (N = 3775) with at least one recorded LDN prescription in 2013 and at least one dispensed opioid prescription during the 365 days preceding the first LDN prescription...
June 2017: Pharmacoepidemiology and Drug Safety
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