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https://www.readbyqxmd.com/read/28970359/investigation-of-diacylglycerol-lipase-alpha-inhibition-in-the-mouse-lipopolysaccharide-inflammatory-pain-model
#1
Jenny L Wilkerson, Giulia Donvito, Travis W Grim, Rehab A Abdullah, Daisuke Ogasawara, Benjamin F Cravatt, Aron H Lichtman
Diacylglycerol lipase (DAGL) α and β, the major biosynthetic enzymes of the endogenous cannabinoid (endocannabinoid) 2-arachidonylglycerol (2-AG), are highly expressed in the nervous system and immune system, respectively. Genetic deletion or pharmacological inhibition of DAGL-β protects against lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages, and reverses LPS-induced allodynia in mice. In order to gain insight into the contribution of DAGL-α in LPS-induced allodynia, we tested global knockout mice as well as DO34, a dual DAGL-α/-β inhibitor...
October 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28940097/expanding-the-genetic-heterogeneity-of-intellectual-disability
#2
Shams Anazi, Sateesh Maddirevula, Vincenzo Salpietro, Yasmine T Asi, Saud Alsahli, Amal Alhashem, Hanan E Shamseldin, Fatema AlZahrani, Nisha Patel, Niema Ibrahim, Firdous M Abdulwahab, Mais Hashem, Nadia Alhashmi, Fathiya Al Murshedi, Adila Al Kindy, Ahmad Alshaer, Ahmed Rumayyan, Saeed Al Tala, Wesam Kurdi, Abdulaziz Alsaman, Ali Alasmari, Selina Banu, Tipu Sultan, Mohammed M Saleh, Hisham Alkuraya, Mustafa A Salih, Hesham Aldhalaan, Tawfeg Ben-Omran, Fatima Al Musafri, Rehab Ali, Jehan Suleiman, Brahim Tabarki, Ayman W El-Hattab, Caleb Bupp, Majid Alfadhel, Nada Al Tassan, Dorota Monies, Stefan T Arold, Mohamed Abouelhoda, Tammaryn Lashley, Henry Houlden, Eissa Faqeih, Fowzan S Alkuraya
Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families...
September 22, 2017: Human Genetics
https://www.readbyqxmd.com/read/28884048/expression-levels-of-%C3%AE-catenin-and-galectin-3-in-meningioma-and-their-effect-on-brain-invasion-and-recurrence-a-tissue-microarray-study
#3
Rehab Allah Ahmed, Abdelhadi M Shebl, Hany Onsy Habashy
OBJECTIVE: Meningiomas are neoplasms that arise from the meninges of the central nervous system (CNS). They constitute about 25.6% of CNS tumors diagnosed in Egypt. Some morphological variants of meningiomas display aggressive behavior, leading to brain-invasive growth pattern. Although meningiomas are usually treated by complete surgical excision, the risk of postoperative recurrence remains. Hence, additional biomarkers for predicting aggressive behavior must be discovered. This study aims to explore the clinical and biological relevance of the protein expression levels of β-catenin and galectine-3 in meningioma and to understand the pathobiology of this neoplasm...
August 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28832656/involvement-of-insulin-resistance-in-d-galactose-induced-age-related-dementia-in-rats-protective-role-of-metformin-and-saxagliptin
#4
Sara Kenawy, Rehab Hegazy, Azza Hassan, Siham El-Shenawy, Nawal Gomaa, Hala Zaki, Amina Attia
Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggest that impaired insulin signaling is the major contributor in the development of Alzheimer's dementia (AD), which is the most common type of senile dementia. In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days)...
2017: PloS One
https://www.readbyqxmd.com/read/28807194/the-impact-of-glasgow-coma-scale-age-prognosis-score-on-geriatric-traumatic-brain-injury-outcomes
#5
Muhammad Khan, Terence O'Keeffe, Faisal Jehan, Narong Kulvatunyou, Abdullah Kattaa, Lynn Gries, Andrew Tang, Bellal Joseph
BACKGROUND: As the population ages, increasing number of geriatric patients sustain traumatic brain injury (TBI). Communication of accurate prognostic information is crucial for making informed decisions on behalf of such patients. Therefore, the aim of our study was to develop a simple and clinically applicable tool that accurately predicts the prognosis in geriatric TBI patients. METHODS: We performed a 1-y (2011) retrospective analysis of isolated geriatric TBI patients (age ≥65 y, head abbreviated injury score [AIS] ≥ 3, and other body AIS < 3) in the National Trauma Data Bank...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28715363/decompressive-craniectomy-vs-craniotomy-only-for-intracranial-hemorrhage-evacuation-a-propensity-matched-study
#6
Faisal Jehan, Asad Azim, Peter Rhee, Muhammad Khan, Lynn Gries, Terence OʼKeeffe, Narong Kulvatunyou, Andrew Tang, Bellal Joseph
BACKGROUND: Decompressive craniectomy (DC) is often performed in conjunction with evacuation of intracranial hemorrhage (ICH) to control intracranial pressure (ICP) in patients with a traumatic brain injury (TBI). The efficacy of DC in lowering ICP is well established, however, its effect on clinical outcomes remains controversial. The aim of our study is to assess outcomes in TBI patients undergoing decompressive craniectomy (DC) vs. craniotomy only (CO) for the evacuation of intracranial hemorrhage...
July 15, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28177688/hepato-and-neuro-protective-influences-of-biopropolis-on-thioacetamide-induced-acute-hepatic-encephalopathy-in-rats
#7
Rasha E Mostafa, Abeer A A Salama, Rehab F Abdel-Rahman, Hanan A Ogaly
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days...
May 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28156162/contribution-of-both-olfactory-and-systemic-pathways-for-brain-targeting-of-nimodipine-loaded-lipo-pluronics-micelles-in-vitro-characterization-and-in-vivo-biodistribution-study-after-intranasal-and-intravenous-delivery
#8
COMPARATIVE STUDY
Hassan M Rashed, Rehab N Shamma, Emad B Basalious
Nimodipine (NM) is the only FDA-approved drug for treating subarachnoid hemorrhage induced vasospasm. NM has poor oral bioavailability (5-13%) due to its low aqueous solubility, and extensive first pass metabolism. The objective of this study is to develop radiolabeled NM-loaded LPM and to test its ability prolong its circulation time, reduce its frequency of administration and eventually target it to the brain tissue. NM was radiolabeled with (99m)Tc by direct labeling method using sodium dithionite. Different reaction conditions that affect the radiolabeling yield were studied...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/27997619/intranasal-chromium-induces-acute-brain-and-lung-injuries-in-rats-assessment-of-different-potential-hazardous-effects-of-environmental-and-occupational-exposure-to-chromium-and-introduction-of-a-novel-pharmacological-and-toxicological-animal-model
#9
Abeer Salama, Rehab Hegazy, Azza Hassan
Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats...
2016: PloS One
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
#10
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...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27495153/w44x-mutation-in-the-wwox-gene-causes-intractable-seizures-and-developmental-delay-a-case-report
#11
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...
August 5, 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
#12
RANDOMIZED CONTROLLED TRIAL
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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