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https://www.readbyqxmd.com/read/28525717/synthesis-and-biological-evaluation-of-novel-neuroprotective-pyridazine-derivatives-as-excitatory-amino-acid-transporter-2-eaat2-activators
#1
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, analysed in comparison with compound 3 in different rat models of oxaliplatin-induced neuropathic pain, showed the better anti-hypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy...
May 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28504556/evolution-of-technique-in-laparoscopic-donor-nephrectomy-a-single-center-experience
#2
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...
May 15, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
March 29, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28342285/development-of-a-human-cadaver-model-for-training-in-laparoscopic-donor-nephrectomy
#10
Erica Sutton, Adrian Billeter, Devin Druen, Henry Roberts, Jonathan Rice, Hiram C Polk
BACKGROUND: The Organ Procurement Network recommends a surgeon record 15 cases as surgeon or assistant for laparoscopic donor nephrectomies (LDN) prior to independent practice. The literature suggests that the learning curve for improved perioperative and patient outcomes is closer to 35 cases. In this article, we describe our development of a model utilizing fresh tissue and objective, quantifiable endpoints to document surgical progress and efficiency in each of the major steps involved in LDN...
March 25, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28270958/laparoscopic-donor-nephrectomy-complications-and-management-a-single-center-experience
#11
Volkan Tuğcu, Selçuk Şahin, İsmail Yiğitbaşı, Nevzat Can Şener, Fatih Gökhan Akbay, Ali İhsan Taşçı
OBJECTIVE: To present our experience with laparoscopic donor nephrectomy (LDN), our complications and management modalities. Material and methods: Fifty-one transperitoneal LDNs performed in our clinic between the years 2011, and 2015, were evaluated retrospectively. Demographic characteristics of the patients, operative and postoperative data and complications were evaluated. RESULTS: Nineteen female and 32 male patients with ages ranging from 24 to 65 years underwent left- (n=44), and right-sided (n=7) LDNs...
March 2017: Turkish Journal of Urology
https://www.readbyqxmd.com/read/28251483/predictive-model-of-1-year-postoperative-renal-function-after-living-donor-nephrectomy
#12
Thibaut Benoit, Xavier Game, Mathieu Roumiguie, Federico Sallusto, Nicolas Doumerc, Jean Baptiste Beauval, Pascal Rischmann, Nassim Kamar, Michel Soulie, Bernard Malavaud
OBJECTIVE: Kidney transplantation from a living donor nephrectomy (LDN) is the best treatment for end-stage renal disease, but decrease in donor renal function is often revealed. The aim of this study was to evaluate the association between preoperative factors and postoperative estimated glomerular filtration rate (eGFR) and test a predictive model to estimate postoperative eGFR, 1 year after LDN. PATIENTS AND METHODS: We reviewed 226 records of consecutive patients who underwent laparoscopic live donor nephrectomy between 2006 and 2014 in a single tertiary center...
March 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28210502/a-single-perioperative-injection-of-dexamethasone-decreases-nausea-vomiting-and-pain-after-laparoscopic-donor-nephrectomy
#13
Shigeyoshi Yamanaga, Andrew Mark Posselt, Chris Earl Freise, Takaaki Kobayashi, Mehdi Tavakol, Sang-Mo Kang
Background. A single dose of perioperative dexamethasone (8-10 mg) reportedly decreases postoperative nausea, vomiting, and pain but has not been widely used in laparoscopic donor nephrectomy (LDN). Methods. We performed a retrospective cohort study of living donors who underwent LDN between 2013 and 2015. Donors who received a lower dose (4-6 mg)  (n = 70) or a higher dose (8-14 mg) of dexamethasone (n = 100) were compared with 111 donors who did not receive dexamethasone (control). Outcomes and incidence of postoperative nausea, vomiting, and pain within 24 h after LDN were compared before and after propensity-score matching...
2017: Journal of Transplantation
https://www.readbyqxmd.com/read/28207159/the-critical-role-of-the-znf217-oncogene-in-promoting-breast-cancer-metastasis-to-the-bone
#14
Aurélie Bellanger, Caterina F Donini, Julie A Vendrell, Jonathan Lavaud, Irma Machuca-Gayet, Maëva Ruel, Julien Vollaire, Evelyne Grisard, Balázs Győrffy, Ivan Bièche, Olivier Peyruchaud, Jean-Luc Coll, Isabelle Treilleux, Véronique Maguer-Satta, Véronique Josserand, Pascale A Cohen
Bone metastasis affects >70% of patients with advanced breast cancer. However, the molecular mechanisms underlying this process remain unclear. On the basis of analysis of clinical datasets, and in vitro and in vivo experiments, we report that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis. Patients with high ZNF217 mRNA expression levels in primary breast tumours had a higher risk of developing bone metastases. MDA-MB-231 breast cancer cells stably transfected with ZNF217 (MDA-MB-231-ZNF217) showed the dysregulated expression of a set of genes with bone-homing and metastasis characteristics, which overlapped with two previously described 'osteolytic bone metastasis' gene signatures, while also highlighting the bone morphogenetic protein (BMP) pathway...
May 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28151933/specific-anti-glycan-antibodies-are-sustained-during-and-after-parasite-clearance-in-schistosoma-japonicum-infected-rhesus-macaques
#15
Y Y Michelle Yang, Xiao Hong Li, Katarzyna Brzezicka, Niels-Christian Reichardt, R Alan Wilson, Angela van Diepen, Cornelis H Hokke
BACKGROUND: Human immunity to Schistosoma infection requires many years of exposure, and multiple infections and treatments to develop. Unlike humans, rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection. In macaques, schistosome egg production decreases after 8 weeks post-infection and by week 22, physiological impairment of the worm caused by unclarified antibody-mediated processes is observed. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28099658/background-noise-analysis-in-urban-airport-surroundings-of-brazilian-cities-congonhas-airport-s%C3%A3-o-paulo
#16
Fabio Scatolini, Cláudio Jorge Pinto Alves
OBJECTIVE: To perform a quantitative analysis of the background noise at Congonhas Airport surroundings based on large sampling and measurements with no interruption. METHODS: Measuring sites were chosen from 62 and 72 DNL (day-night-level) noise contours, in urban sites compatible with residential use. Fifteen sites were monitored for at least 168 hours without interruption or seven consecutive days. Data compilation was based on cross-reference between noise measurements and air traffic control records, and results were validated by airport meteorological reports...
December 22, 2016: Revista de Saúde Pública
https://www.readbyqxmd.com/read/28087899/increasing-dietary-nitrate-has-no-effect-on-cancellous-bone-loss-or-fecal-microbiome-in-ovariectomized-rats
#17
Melissa N Conley, Cooper Roberts, Thomas J Sharpton, Urszula T Iwaniec, Norman G Hord
SCOPE: Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age-related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. METHODS AND RESULTS: Six-month-old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham-operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low-dose nitrate (LDN, 0...
May 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28052036/angiomotin-regulates-prostate-cancer-cell-proliferation-by-signaling-through-the-hippo-yap-pathway
#18
Hao Zeng, Angelica Ortiz, Peng-Fei Shen, Chien-Jui Cheng, Yu-Chen Lee, Guoyu Yu, Song-Chang Lin, Chad J Creighton, Li-Yuan Yu-Lee, Sue-Hwa Lin
Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3, DU145, and BPH1 cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28029219/defining-the-tipping-point-in-surgical-performance-for-laparoscopic-donor-nephrectomy-among-transplant-surgery-fellows-a-risk-adjusted-cumulative-summation-learning-curve-analysis
#19
O K Serrano, A S Bangdiwala, D M Vock, D Berglund, T B Dunn, E B Finger, T L Pruett, A J Matas, R Kandaswamy
The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship...
December 28, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28005976/relationship-of-transportation-noise-and-annoyance-for-two-metropolitan-cities-in-korea-population-based-study
#20
Joo Hyun Sung, Jiho Lee, Sang Jin Park, Chang Sun Sim
Transportation noise is known to have negative impact on both public health and life quality. This study evaluated the relationship between transportation noise and annoyance levels, and also the difference of annoyance levels in two metropolitan cities based on epidemiologic surveys. Two thousand adult subjects living in Seoul and Ulsan were enrolled by stratified random sampling on the basis of noise maps from July 2015 to January 2016. Individual annoyance in accordance with transportation noise levels in two metropolitan cities were surveyed using an 11-point visual analog scale questionnaire...
2016: PloS One
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