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https://www.readbyqxmd.com/read/27890602/the-endocannabinoid-hydrolysis-inhibitor-sa-57-intrinsic-antinociceptive-effects-augmented-morphine-induced-antinociception-and-attenuated-heroin-seeking-behavior-in-mice
#1
Jenny L Wilkerson, Sudeshna Ghosh, Mohammed Mustafa, Rehab A Abdullah, Micah J Niphakis, Roberto Cabrera, Rafael L Maldonado, Benjamin F Cravatt, Aron H Lichtman
Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class...
November 24, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27495153/w44x-mutation-in-the-wwox-gene-causes-intractable-seizures-and-developmental-delay-a-case-report
#2
Loai Elsaadany, Mahmoud El-Said, Rehab Ali, Hussein Kamel, Tawfeg Ben-Omran
BACKGROUND: WW domain containing oxidoreductase (WWOX) gene was cloned in 2000; alteration has been seen in many cancer cells. It acts as a tumor suppresser by blocking cell growth and causing apoptosis. WWOX protein showed different expression of mice brain and spinal cord, for which deletion causes seizure and early death. CASE PRESENTATION: Clinical and molecular characteristics of a consanguineous family show a homozygous mutation of WWOX gene at specific bases, causing a debilitating syndrome characterized by growth retardation, intractable epilepsy, intellectual disability, and early death...
2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27447483/effectiveness-of-a-very-early-stepping-verticalization-protocol-in-severe-acquired-brain-injured-patients-a-randomized-pilot-study-in-icu
#3
Giuseppe Frazzitta, Ilaria Zivi, Roberto Valsecchi, Sara Bonini, Sara Maffia, Katia Molatore, Luca Sebastianelli, Alessio Zarucchi, Diana Matteri, Giuseppe Ercoli, Roberto Maestri, Leopold Saltuari
BACKGROUND AND OBJECTIVE: Verticalization was reported to improve the level of arousal and awareness in patients with severe acquired brain injury (ABI) and to be safe in ICU. We evaluated the effectiveness of a very early stepping verticalization protocol on their functional and neurological outcome. METHODS: Consecutive patients with Vegetative State or Minimally Conscious State were enrolled in ICU on the third day after an ABI. They were randomized to undergo conventional physiotherapy alone or associated to fifteen 30-minute sessions of verticalization, using a tilt table with robotic stepping device...
2016: PloS One
https://www.readbyqxmd.com/read/27297242/day-of-surgery-impacts-outcome-rehabilitation-utilization-on-hospital-length-of-stay-in-patients-undergoing-elective-meningioma-resection
#4
Christopher A Sarkiss, Joseph A Papin, Amy Yao, James Lee, Roberta K Sefcik, Eric K Oermann, Errol L Gordon, Kalmon D Post, Joshua B Bederson, Raj K Shrivastava
OBJECTIVE/BACKGROUND: Meningiomas account for approximately one third of all brain tumors in the United States. In high-volume medical centers, the average length of stay (LOS) for a patient is 6.8 days compared with 8.8 days in low-volume centers with median total admission charges equaling approximately $55,000. To our knowledge, few studies have evaluated day of surgery and its effect on hospital LOS. Our primary goal was to analyze patient outcome as a direct result of surgical date, as well as to characterize the individual variables that may impact their hospital course, early access to rehabilitation, and long-term functional status...
September 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27128792/trans-nasal-zolmitriptan-novasomes-in-vitro-preparation-optimization-and-in-vivo-evaluation-of-brain-targeting-efficiency
#5
Radwa M A Abd-Elal, Rehab N Shamma, Hassan M Rashed, Ehab R Bendas
Migraine attack is a troublesome physiological condition associated with throbbing, intense headache, in one half of the head. Zolmitriptan is a potent second-generation triptan, prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. The absolute bioavailability of zolmitriptan is about 40% for oral administration; due to hepatic first metabolism. Nasal administration would circumvent the pre-systemic metabolism thus increasing the bioavailability of zolmitriptan. In addition, due to the presence of microvilli and high vasculature, the absorption is expected to be faster compared to oral route...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/26726854/positive-psychotherapy-in-abi-rehab-popstar-a-pilot-randomised-controlled-trial
#6
Breda Cullen, Jaycee Pownall, Joanne Cummings, Satu Baylan, Niall Broomfield, Caroline Haig, Denyse Kersel, Heather Murray, Jonathan J Evans
Psychological distress is common following acquired brain injury (ABI), but the evidence base for psychotherapeutic interventions is small and equivocal. Positive psychotherapy aims to foster well-being by increasing experiences of pleasure, engagement and meaning. In this pilot trial, we investigated the feasibility and acceptability of brief positive psychotherapy in adults with ABI and emotional distress. Participants were randomised to brief positive psychotherapy plus usual treatment, or usual treatment only...
January 4, 2016: Neuropsychological Rehabilitation
https://www.readbyqxmd.com/read/26644915/vitamin-d-and-the-skin-focus-on-a-complex-relationship-a-review
#7
REVIEW
Wedad Z Mostafa, Rehab A Hegazy
The "sunshine" vitamin is a hot topic that attracted ample attention over the past decades, specially that a considerable proportion of the worldwide population are deficient in this essential nutrient. Vitamin D was primarily acknowledged for its importance in bone formation, however; increasing evidence point to its interference with the proper function of nearly every tissue in our bodies including brain, heart, muscles, immune system and skin. Thereby its deficiency has been incriminated in a long panel of diseases including cancers, autoimmune diseases, cardiovascular and neurological disorders...
November 2015: Journal of Advanced Research
https://www.readbyqxmd.com/read/26541329/endocannabinoid-regulation-of-nausea-is-mediated-by-2-arachidonoylglycerol-2-ag-in-the-rat-visceral-insular-cortex
#8
Martin A Sticht, Cheryl L Limebeer, Benjamin R Rafla, Rehab A Abdullah, Justin L Poklis, Winnie Ho, Micah J Niphakis, Benjamin F Cravatt, Keith A Sharkey, Aron H Lichtman, Linda A Parker
Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown. Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea. In the present study, we assessed whether inhibiting the primary endocannabinoid hydrolytic enzymes in the VIC reduces acute lithium chloride (LiCl)-induced conditioned gaping, a rat model of nausea...
March 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26241752/novel-self-assembled-nano-tubular-mixed-micelles-of-pluronics-p123-pluronic-f127-and-phosphatidylcholine-for-oral-delivery-of-nimodipine-in-vitro-characterization-ex-vivo-transport-and-in-vivo-pharmacokinetic-studies
#9
Emad B Basalious, Rehab N Shamma
Subarachnoid hemorrhage (SAH) is a major cause of death in patients suffering from stroke. Nimodipine (NM) is the only FDA-approved drug for treating SAH-induced vasospasm. However, NM suffers from poor oral bioavailability (5-13%) due to its low aqueous solubility, extensive first pass metabolism and short elimination half-life (1-2h). The objective of this study was to develop NM-loaded Pluronic/phosphatidylcholine/polysorbate 80 mixed micelles (PPPMM) that can solubilize NM in aqueous media even after dilution, prolong its circulation time, improve its bioavailability and eventually help in targeting it to the brain tissue...
September 30, 2015: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/26077850/high-diagnostic-yield-of-clinical-exome-sequencing-in-middle-eastern-patients-with-mendelian-disorders
#10
Tarunashree Yavarna, Nader Al-Dewik, Mariam Al-Mureikhi, Rehab Ali, Fatma Al-Mesaifri, Laila Mahmoud, Noora Shahbeck, Shenela Lakhani, Mariam AlMulla, Zafar Nawaz, Patrik Vitazka, Fowzan S Alkuraya, Tawfeg Ben-Omran
Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qatar with suspected Mendelian, mainly neurocognitive phenotypes, underwent CES from July 2012 to June 2014. Intellectual disability and global developmental delay were the most common clinical presentations but our cohort displayed other phenotypes, such as epilepsy, dysmorphism, microcephaly and other structural brain anomalies and autism...
September 2015: Human Genetics
https://www.readbyqxmd.com/read/26058501/vagus-nerve-stimulation-delivered-with-motor-training-enhances-recovery-of-function-after-traumatic-brain-injury
#11
David T Pruitt, Ariel N Schmid, Lily J Kim, Caroline M Abe, Jenny L Trieu, Connie Choua, Seth A Hays, Michael P Kilgard, Robert L Rennaker
Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly 2 million people every year. The effects of TBI, including weakness and loss of coordination, can be debilitating and last years after the initial injury. Recovery of motor function is often incomplete. We have developed a method using electrical stimulation of the vagus nerve paired with forelimb use by which we have demonstrated enhanced recovery from ischemic and hemorrhagic stroke. Here we have tested the hypothesis that vagus nerve stimulation (VNS) paired with physical rehabilitation could enhance functional recovery after TBI...
May 1, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/26015920/a-study-of-blood-serotonin-and-serotonin-transporter-promoter-variant-5-httlpr-polymorphism-in-egyptian-autistic-children
#12
Nagwa A Meguid, Ola H Gebril, Rehab O Khalil
BACKGROUND: Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders...
2015: Advanced Biomedical Research
https://www.readbyqxmd.com/read/25998048/full-fatty-acid-amide-hydrolase-inhibition-combined-with-partial-monoacylglycerol-lipase-inhibition-augmented-and-sustained-antinociceptive-effects-with-reduced-cannabimimetic-side-effects-in-mice
#13
Sudeshna Ghosh, Steven G Kinsey, Qing-Song Liu, Lenka Hruba, Lance R McMahon, Travis W Grim, Christina R Merritt, Laura E Wise, Rehab A Abdullah, Dana E Selley, Laura J Sim-Selley, Benjamin F Cravatt, Aron H Lichtman
Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception but with minimal cannabimimetic side effects. Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents another challenge in this potential therapeutic strategy...
August 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/25972803/critical-periods-after-stroke-study-translating-animal-stroke-recovery-experiments-into-a-clinical-trial
#14
Alexander W Dromerick, Matthew A Edwardson, Dorothy F Edwards, Margot L Giannetti, Jessica Barth, Kathaleen P Brady, Evan Chan, Ming T Tan, Irfan Tamboli, Ruth Chia, Michael Orquiza, Robert M Padilla, Amrita K Cheema, Mark E Mapstone, Massimo S Fiandaca, Howard J Federoff, Elissa L Newport
INTRODUCTION: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans...
2015: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/25803957/acute-stroke-unit-improves-stroke-management-four-years-on-from-inasc
#15
E Shanahan, R Keenan, N Cunningham, G O'Malley, M O'Connor, D Lyons, C Peters
The Irish Heart Foundation carried out the Irish National Audit of Stroke Care (INASC) in 2008. Management practices were significantly poorer than those in the UK Sentinel audits. Since then an acute stroke unit has been established in University Hospital Limerick. A stroke database was established. 12 key indicators of stroke management audited by INASC were identified. Results were compared to those in INASC. 89 stroke patients were admitted. 8 of the 12 key indicators scored significantly better than in INASC...
February 2015: Irish Medical Journal
https://www.readbyqxmd.com/read/25762694/selective-monoacylglycerol-lipase-inhibitors-antinociceptive-versus-cannabimimetic-effects-in-mice
#16
Bogna Ignatowska-Jankowska, Jenny L Wilkerson, Mohammed Mustafa, Rehab Abdullah, Micah Niphakis, Jenny L Wiley, Benjamin F Cravatt, Aron H Lichtman
The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) plays an important role in a variety of physiologic processes, but its rapid breakdown by monoacylglycerol lipase (MAGL) results in short-lived actions. Initial MAGL inhibitors were limited by poor selectivity and low potency. In this study, we tested JZL184 [4-nitrophenyl 4-[bis(2H-1,3-benzodioxol-5-yl)(hydroxy)methyl]piperidine-1-carboxylate] and MJN110 [2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate], MAGL inhibitors that possess increased selectivity and potency, in mouse behavioral assays of neuropathic pain [chronic constriction injury (CCI) of the sciatic nerve], interoceptive cannabimimetic effects (drug-discrimination paradigm), and locomotor activity in an open field test...
May 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/25398241/%C3%AE-9-tetrahydrocannabinol-and-endocannabinoid-degradative-enzyme-inhibitors-attenuate-intracranial-self-stimulation-in-mice
#17
Jason M Wiebelhaus, Travis W Grim, Robert A Owens, Matthew F Lazenka, Laura J Sim-Selley, Rehab A Abdullah, Micah J Niphakis, Robert E Vann, Benjamin F Cravatt, Jenny L Wiley, S Stevens Negus, Aron H Lichtman
A growing body of evidence implicates endogenous cannabinoids as modulators of the mesolimbic dopamine system and motivated behavior. Paradoxically, the reinforcing effects of Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, have been difficult to detect in preclinical rodent models. In this study, we investigated the impact of THC and inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on operant responding for electrical stimulation of the medial forebrain bundle [intracranial self-stimulation (ICSS)], which is known to activate the mesolimbic dopamine system...
February 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/25085768/effect-of-selective-inhibition-of-monoacylglycerol-lipase-magl-on-acute-nausea-anticipatory-nausea-and-vomiting-in-rats-and-suncus-murinus
#18
Linda A Parker, Micah J Niphakis, Rachel Downey, Cheryl L Limebeer, Erin M Rock, Martin A Sticht, Heather Morris, Rehab A Abdullah, Aron H Lichtman, Benjamin F Cravatt
RATIONALE: To determine the role of the endocannabinoid, 2-arachodonyl glycerol (2-AG), in the regulation of nausea and vomiting. OBJECTIVE: We evaluated the effectiveness of the potent selective monoacylglycerol lipase (MAGL) inhibitor, MJN110, which selectively elevates the endocannabinoid 2-AG, to suppress acute nausea and vomiting, as well as anticipatory nausea in rat and shrew models. METHODS: The rat gaping models were used to evaluate the potential of MJN110 (5, 10, and 20 mg/kg, intraperitoneally [IP]) to suppress acute nausea produced by LiCl and of MJN110 (10 and 20 mg/kg, IP) to suppress anticipatory nausea elicited by a LiCl-paired context...
February 2015: Psychopharmacology
https://www.readbyqxmd.com/read/24907849/mutations-in-zinc-finger-407-znf407-cause-a-unique-autosomal-recessive-cognitive-impairment-syndrome
#19
Marios Kambouris, Rachid C Maroun, Tawfeg Ben-Omran, Yasser Al-Sarraj, Khaoula Errafii, Rehab Ali, Hala Boulos, Patrick A Curmi, Hatem El-Shanti
BACKGROUND: A consanguineous Arab family is affected by an apparently novel autosomal recessive disorder characterized by cognitive impairment, failure-to-thrive, hypotonia and dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally. METHODS: The family was studied by homozygosity mapping, candidate gene mutation screening and whole Exome Next Generation Sequencing of a single affected member to identify the offending gene and mutation...
2014: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/24849924/prolonged-monoacylglycerol-lipase-blockade-causes-equivalent-cannabinoid-receptor-type-1-receptor-mediated-adaptations-in-fatty-acid-amide-hydrolase-wild-type-and-knockout-mice
#20
Joel E Schlosburg, Steven G Kinsey, Bogna Ignatowska-Jankowska, Divya Ramesh, Rehab A Abdullah, Qing Tao, Lamont Booker, Jonathan Z Long, Dana E Selley, Benjamin F Cravatt, Aron H Lichtman
Complementary genetic and pharmacological approaches to inhibit monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), the primary hydrolytic enzymes of the respective endogenous cannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine, enable the exploration of potential therapeutic applications and physiologic roles of these enzymes. Complete and simultaneous inhibition of both FAAH and MAGL produces greatly enhanced cannabimimetic responses, including increased antinociception, and other cannabimimetic effects, far beyond those seen with inhibition of either enzyme alone...
August 2014: Journal of Pharmacology and Experimental Therapeutics
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