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https://www.readbyqxmd.com/read/28697406/efficacy-of-pharmacologic-closure-of-patent-ductus-arteriosus-in-small-for-gestational-age-extremely-preterm-infants
#1
Nansi S Boghossian, Barbara T Do, Edward F Bell, John M Dagle, Jane E Brumbaugh, Barbara J Stoll, Betty R Vohr, Abhik Das, Seetha Shankaran, Pablo J Sanchez, Myra H Wyckoff, M Bethany Ball
BACKGROUND: Optimal management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Therefore, studies identifying infants who are most likely to benefit from PDA treatment are needed. AIM: We sought to examine if significant intrauterine growth restriction, defined by birth weight z-score, reduces the efficacy of PDA closure with indomethacin or ibuprofen and thereby increases the need for surgical closure of PDA after pharmacologic treatment...
July 8, 2017: Early Human Development
https://www.readbyqxmd.com/read/28609431/polymorphisms-in-urea-cycle-enzyme-genes-are-associated-with-persistent-pulmonary-hypertension-of-the-newborn
#2
Dinushan C Kaluarachchi, Caitlin J Smith, Jonathan M Klein, Jeffrey C Murray, John M Dagle, Kelli K Ryckman
BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance. Endogenous nitric oxide is critical for regulation of pulmonary vascular resistance. Nitric oxide is generated from L -arginine, supplied by the urea cycle (UC). We hypothesized that polymorphisms in UC enzyme genes and low concentrations of UC intermediates are associated with PPHN. METHODS: We performed a family based candidate gene analysis to study 48 single nucleotide polymorphisms (SNPs) in 6 UC enzyme genes...
June 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28609430/polymorphisms-in-cyp2c9-are-associated-with-response-to-indomethacin-among-neonates-with-patent-ductus-arteriosus
#3
Caitlin J Smith, Kelli K Ryckman, Timothy M Bahr, John M Dagle
BackgroundPatent ductus arteriosus (PDA) is a common complication seen in preterm infants. Indomethacin is routinely used to treat PDA. Evidence suggests that the response of indomethacin is highly heritable. This study investigated the association between single-nucleotide polymorphisms (SNPs) in CYP2C9 and the closure of PDA in response to indomethacin.MethodsSix SNPs in CYP2C9 were analyzed for association with indomethacin response. A case-control analysis was performed among neonates who responded to indomethacin (responders) and among those who required surgical ligation (non-responders)...
July 5, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28589628/chemical-tools-to-modulate-2-ag-biosynthesis
#4
Hui Deng, Mario van der Stelt
2-Arachidonoylglycerol (2-AG) as an important endogenous signaling lipid that activates the cannabinoid receptors (CB1 R and CB2 R), thereby regulating a diverse range of physiological processes including anxiety, appetite, inflammation, memory, pain sensation and nociception. Diacylglycerol lipases (DAGLs) are the principle enzymes responsible for 2-AG biosynthesis. Recently, the (patho)physiological functions of DAGLs have been explored by both genetic methods and chemical tools. This review will focus on the recent efforts to develop highly selective and in vivo active DAGLs inhibitors using activity-based protein profiling...
June 6, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28549792/endocannabinoids-modulate-apoptosis-in-endometriosis-and-adenomyosis
#5
Elif Bilgic, Elif Guzel Meydanli, Sevil Kose, Makbule Cisel Aydin, Eda Karaismailoglu, Irem Akar, Alp Usubutun, Petek Korkusuz
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues...
May 23, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28249118/antenatal-determinants-of-bronchopulmonary-dysplasia-and-late-respiratory-disease-in-preterm-infants
#6
Lindsey A Morrow, Brandie D Wagner, David A Ingram, Brenda B Poindexter, Kurt Schibler, C Michael Cotten, John Dagle, Marci K Sontag, Peter M Mourani, Steven H Abman
Rationale/Objectives: To identify antenatal risk factors associated with increased risk for BPD and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age <34 weeks and birth weights between 500-1250 grams. METHODS: Data included perinatal information and assessments during the NICU admission and longitudinal follow-up by questionnaire until 2 years of age. RESULTS: After adjusting for covariates, maternal smoking prior to preterm birth increased the odds of having an infant with BPD by 2-fold(p=0...
March 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28106377/chemical-proteomics-maps-brain-region-specific-activity-of-endocannabinoid-hydrolases
#7
Marc P Baggelaar, Annelot C M van Esbroeck, Eva J van Rooden, Bogdan I Florea, Herman S Overkleeft, Giovanni Marsicano, Francis Chaouloff, Mario van der Stelt
The biosynthetic and catabolic enzymes of the endocannabinoids tightly regulate endocannabinoid-mediated activation of the cannabinoid CB1 receptor. Monitoring the activities of these endocannabinoid hydrolases in different brain regions is, therefore, key to gaining insight into spatiotemporal control of CB1 receptor-mediated physiology. We have employed a comparative chemical proteomics approach to quantitatively map the activity profile of endocannabinoid hydrolases in various mouse brain regions at the same time...
March 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28069688/upregulation-of-cb2-receptors-in-reactive-astrocytes-in-canine-degenerative-myelopathy-a-disease-model-of-amyotrophic-lateral-sclerosis
#8
María Fernández-Trapero, Francisco Espejo-Porras, Carmen Rodríguez-Cueto, Joan R Coates, Carmen Pérez-Díaz, Eva de Lago, Javier Fernández-Ruiz
Targeting of the CB2 receptor results in neuroprotection in the SOD1(G93A) mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1)...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27992221/triazole-ureas-act-as-diacylglycerol-lipase-inhibitors-and-prevent-fasting-induced-refeeding
#9
Hui Deng, Sander Kooijman, Adrianus M C H van den Nieuwendijk, Daisuke Ogasawara, Tom van der Wel, Floris van Dalen, Marc P Baggelaar, Freek J Janssen, Richard J B H N van den Berg, Hans den Dulk, Benjamin F Cravatt, Herman S Overkleeft, Patrick C N Rensen, Mario van der Stelt
Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold...
December 19, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27893720/a-functional-atg16l1-t300a-variant-is-associated-with-necrotizing-enterocolitis-in-premature-infants
#10
Venkatesh Sampath, Vineet Bhandari, Jessica Berger, Daniel Merchant, Liyun Zhang, Mihoko Ladd, Heather Menden, Jeffery Garland, Namasivayam Ambalavanan, Neil Mulrooney, Michael Quasney, John Dagle, Pascal M Lavoie, Pippa Simpson, Mary Dahmer
BACKGROUND: The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) and autophagy (ATG) genes modulate vulnerability to NEC. METHODS: We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8, and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis...
April 2017: Pediatric Research
https://www.readbyqxmd.com/read/27784678/oxyradical-stress-increases-the-biosynthesis-of-2-arachidonoylglycerol-involvement-of-nadph-oxidase
#11
Anberitha T Matthews, Jung Hwa Lee, Abdolsamad Borazjani, Lee C Mangum, Xiang Hou, Matthew K Ross
NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-β (DAGL-β), the 2-AG biosynthetic enzyme...
December 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27778288/competitive-abpp-of-serine-hydrolases-a-case-study-on-dagl-alpha
#12
Marc P Baggelaar, Mario Van der Stelt
Competitive activity-based protein profiling is a highly efficient chemical biology technique to determine target engagement and selectivity profiles of enzyme inhibitors in complex proteomes. Fluorophosphonate-based fluorescent inhibitors are widely used as broad-spectrum probes for serine hydrolases. However, diacylglycerol lipase-α is not labeled by fluorophosphonate-based probes. To overcome this problem, we have developed a tailor-made activity-based probe that reacts with diacylglycerol lipase-α. Here we describe a case study in which we apply competitive activity-based protein profiling using a broad-spectrum and a tailor-made activity-based probe to establish selectivity and activity profiles of inhibitors targeting diacylglycerol lipase-α in the mouse brain proteome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27766867/therapeutic-potential-of-fatty-acid-amide-hydrolase-monoacylglycerol-lipase-and-n-acylethanolamine-acid-amidase-inhibitors
#13
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27552286/fabp1-a-novel-hepatic-endocannabinoid-and-cannabinoid-binding-protein
#14
Huan Huang, Avery L McIntosh, Gregory G Martin, Danilo Landrock, Sarah Chung, Kerstin K Landrock, Lawrence J Dangott, Shengrong Li, Ann B Kier, Friedhelm Schroeder
Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG)...
September 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27516570/metabolism-of-endocannabinoids
#15
REVIEW
Michał Biernacki, Elżbieta Skrzydlewska
Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown...
August 11, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27448020/orexins-contribute-to-restraint-stress-induced-cocaine-relapse-by-endocannabinoid-mediated-disinhibition-of-dopaminergic-neurons
#16
Li-Wei Tung, Guan-Ling Lu, Yen-Hsien Lee, Lung Yu, Hsin-Jung Lee, Emma Leishman, Heather Bradshaw, Ling-Ling Hwang, Ming-Shiu Hung, Ken Mackie, Andreas Zimmer, Lih-Chu Chiou
Orexins are associated with drug relapse in rodents. Here, we show that acute restraint stress in mice activates lateral hypothalamic (LH) orexin neurons, increases levels of orexin A and 2-arachidonoylglycerol (2-AG) in the ventral tegmental area (VTA), and reinstates extinguished cocaine-conditioned place preference (CPP). This stress-induced reinstatement of cocaine CPP depends on type 1 orexin receptors (OX1Rs), type 1 cannabinoid receptors (CB1Rs) and diacylglycerol lipase (DAGL) in the VTA. In dopaminergic neurons of VTA slices, orexin A presynaptically inhibits GABAergic transmission...
2016: Nature Communications
https://www.readbyqxmd.com/read/27394666/inhibitors-of-diacylglycerol-lipases-in-neurodegenerative-and-metabolic-disorders
#17
REVIEW
Freek J Janssen, Mario van der Stelt
2-Arachidonoylglycerol (2-AG) is an endocannabinoid that activates the cannabinoid receptors type 1 and 2. It also serves as an important lipid precursor for the eicosanoid signaling pathway. Consequently, 2-AG is involved in many physiological functions, including anxiety, food intake, inflammation, memory, pain sensation and neurotransmission. Diacylglycerol lipases (DAGLs) are the main biosynthetic enzymes for 2-AG and their role in several pathophysiological conditions is currently under investigation. In this Digest we review all DAGL inhibitors reported to date and their effects in preclinical models of neurodegeneration and metabolic disorders...
August 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27355428/age-related-changes-in-retinoic-docosahexaenoic-and-arachidonic-acid-modulation-in-nuclear-lipid-metabolism
#18
Virginia L Gaveglio, Ana C Pascual, Norma M Giusto, Susana J Pasquaré
The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity...
August 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27344223/genetic-modifiers-of-patent-ductus-arteriosus-in-term-infants
#19
Priti M Patel, Allison M Momany, Kendra L Schaa, Paul A Romitti, Charlotte Druschel, Margaret E Cooper, Mary L Marazita, Jeffrey C Murray, John M Dagle
OBJECTIVE: To identify single-nucleotide polymorphisms (SNPs) in specific candidate genes associated with patent ductus arteriosus in term infants. STUDY DESIGN: We conducted an initial family-based, candidate gene study to analyze genotype data from DNA samples obtained from 171 term infants and their parents enrolled in the National Birth Defects Prevention Study (NBDPS). We performed transmission disequilibrium testing (TDT) using a panel of 55 SNPs in 17 genes...
September 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27327781/the-endocannabinoid-system-in-the-baboon-papio-spp-as-a-complex-framework-for-developmental-pharmacology
#20
Iram P Rodriguez-Sanchez, Josee Guindon, Marco Ruiz, M Elizabeth Tejero, Gene Hubbard, Laura E Martinez-de-Villarreal, Hugo A Barrera-Saldaña, Edward J Dick, Anthony G Comuzzie, Natalia E Schlabritz-Loutsevitch
INTRODUCTION: The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha)...
November 2016: Neurotoxicology and Teratology
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