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https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#1
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28531297/mechanisms-of-kappa-opioid-receptor-potentiation-of-dopamine-d2-receptor-function-in-quinpirole-induced-locomotor-sensitization-in-rats
#2
Angélica P Escobar, Marcela P González, Rodrigo C Meza, Verónica Noches, Pablo Henny, Katia Gysling, Rodrigo A España, José A Fuentealba, María E Andrés
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of Quinpirole (QNP), a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist (KOR). The mechanism underlying KOR potentiation of QNP-induced locomotor sensitization remains to be elucidated...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28528529/the-influence-of-depolarization-block-on-seizure-like-activity-in-networks-of-excitatory-and-inhibitory-neurons
#3
Christopher M Kim, Duane Q Nykamp
The inhibitory restraint necessary to suppress aberrant activity can fail when inhibitory neurons cease to generate action potentials as they enter depolarization block. We investigate possible bifurcation structures that arise at the onset of seizure-like activity resulting from depolarization block in inhibitory neurons. Networks of conductance-based excitatory and inhibitory neurons are simulated to characterize different types of transitions to the seizure state, and a mean field model is developed to verify the generality of the observed phenomena of excitatory-inhibitory dynamics...
May 20, 2017: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/28528394/a-novel-dual-wavelength-laser-stimulator-to-elicit-transient-and-tonic-nociceptive-stimulation
#4
Xiaoxi Dong, Tianjun Liu, Han Wang, Jichun Yang, Zhuying Chen, Yong Hu, Yingxin Li
This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain...
May 20, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28528287/population-pharmacokinetics-of-oxcarbazepine-and-its-metabolite-10-hydroxycarbazepine-in-healthy-subjects
#5
Natalicia de Jesus Antunes, Sven C van Dijkman, Vera Lucia Lanchote, Lauro Wichert-Ana, Eduardo Barbosa Coelho, Veriano Alexandre Junior, Osvaldo Massaiti Takayanagui, Eduardo Tozatto, Johan G C van Hasselt, Oscar Della Pasqua
Oxcarbazepine is indicated for the treatment of partial or generalized tonic-clonic seizures. The majority of the oxcarbazepine is converted into its active metabolite, 10-hydroxycarbazepine (MHD), which can exist as R-(-)- and S-(+)-MHD enantiomers. Here we describe the influence of the P-glycoprotein (P-gp) inhibitor verapamil, on the disposition of oxcarbazepine and MHD enantiomers, both of which are P-gp substrates. Healthy subjects (n=12) were randomized to oxcarbazepine or oxcarbazepine combined with verapamil at doses of 300mg b...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28526694/measuring-osmosis-and-hemolysis-of-red-blood-cells
#6
Lauren K Goodhead, Frances M MacMillan
Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28526693/a-simple-laboratory-exercise-with-rat-isolated-esophagus-and-stomach-fundus-to-reveal-functional-differences-between-striated-and-smooth-muscle-cells
#7
Francisco José Batista-Lima, Kalinne Kelly Lima Gadelha, Daniel Maia Oliveira, Thiago Brasileiro Vasconcelos, Teresinha Silva Brito, Pedro Jorge Caldas Magalhães
This study describes an undergraduate student laboratory activity using isolated preparations from rat gastrointestinal tissues that possess contractile profiles typically exhibited by striated and smooth muscle cells. While students are introduced to an ex vivo methodology, they can compare differences in trace experiments, twitch aspects, phasic and tonic properties, force-frequency relationships, and pharmacological responsiveness of esophageal (striated) and fundic (smooth muscle) segments. Muscle strips were subjected to electrical field stimulation (EFS) applied by platinum electrodes immersed in the physiological solution...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28524796/improvement-of-visual-field-defects-after-focal-resection-for-occipital-lobe-epilepsy-case-report
#8
Takahiro Yamamoto, Tadashi Hamasaki, Hideo Nakamura, Kazumichi Yamada
Improvement of visual field defects after surgical treatment for occipital lobe epilepsy is rare. Here, the authors report on a 24-year-old man with a 15-year history of refractory epilepsy that developed after he had undergone an occipital craniotomy to remove a cerebellar astrocytoma at the age of 4. His seizures started with an elementary visual aura, followed by secondary generalized tonic-clonic convulsion. Perimetry revealed left-sided incomplete hemianopia, and MRI showed an old contusion in the right occipital lobe...
May 19, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28524260/presence-of-ethanol-sensitive-glycine-receptors-in-medium-spiny-neurons-in-the-mouse-nucleus-accumbens
#9
B Förstera, B Muñoz, M K Lobo, R Chandra, D M Lovinger, L G Aguayo
Alcohol abuse causes major social, economic and health-related problems worldwide. Alcohol, like other drugs of abuse, increases levels of dopamine in the nucleus accumbens, facilitating behavioural reinforcement and substance abuse. Previous studies suggested that glycine receptors (GlyRs) are involved in the regulation of accumbal dopamine levels. Here, we investigated the presence of GlyRs in accumbal dopamine receptor medium spiny neurons (MSNs) of C57BL/6J mice, analyzing mRNA expression-levels and immunoreactivity of GlyR subunits, as well as ethanol sensitivity...
May 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28523600/sodium-channel-blockers-in-the-treatment-of-epilepsy
#10
Martin J Brodie
Sodium channel blockers have been the mainstay of the pharmacological management of focal and generalised tonic-clonic seizures for more than 70 years. The focus of this paper will be on phenytoin, carbamazepine, lamotrigine, oxcarbazepine, rufinamide, lacosamide and eslicarbazepine acetate. All these antiepileptic drugs have similar efficacy and share similar dose-dependent, adverse effect profiles, although phenytoin, carbamazepine and oxcarbazepine are more likely to cause idiosyncratic reactions than the others...
May 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28523059/efficacy-and-safety-of-optic-nerve-sheath-fenestration-in-patients-with-raised-intracranial-pressure
#11
Muhammad Amer Yaqub, Mohammad Asim Mehboob, Qamar Ul Islam
OBJECTIVE: To evaluate the efficacy and safety of Optic Nerve Sheath Fenestration (ONSF) in patients with raised intracranial pressure (ICP). METHODS: This Quasi Experimental Study was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi from July 2013 to July 2015. Thirty one eyes of 18 patients who underwent ONSF for raised ICP were followed up for one year to ascertain efficacy and safety of ONSF procedure. RESULTS: Thirteen (72...
March 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28522678/cigarette-smoking-associated-alterations-in-serotonin-adrenalin-signaling-pathways-of-platelets
#12
Curtis Lee Lowery, Clay Elliott, Anthonya Cooper, Coedy Hadden, Roberto N Sonon, Parastoo Azadi, D Keith Williams, James D Marsh, Donna S Woulfe, Fusun Kilic
BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system-mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5-HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28520883/effect-of-isotonic-versus-hypotonic-maintenance-fluid-therapy-on-urine-output-fluid-balance-and-electrolyte-homeostasis-a-crossover-study-in-fasting-adult-volunteers
#13
N Van Regenmortel, T De Weerdt, A H Van Craenenbroeck, E Roelant, W Verbrugghe, K Dams, M L N G Malbrain, T Van den Wyngaert, P G Jorens
Background.: Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload. Methods.: This crossover study consisted of two 48 h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0...
May 16, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28518111/using-enzyme-based-biosensors-to-measure-tonic-and-phasic-glutamate-in-alzheimer-s-mouse-models
#14
Holly C Hunsberger, Sharay E Setti, Ryan T Heslin, Jorge E Quintero, Greg A Gerhardt, Miranda N Reed
Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying Alzheimer's disease, Parkinson's disease, depression, and anxiety. Traditionally, microdialysis has been the most common (lauded) technique to examine neurotransmitter changes that occur in these disorders. But because microdialysis has the ability to measure slow 1-20 minute changes across large areas of tissue, it has the disadvantage of invasiveness, potentially destroying intrinsic connections within the brain and a slow sampling capability...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28513860/cortical-contributions-to-sensory-gating-in-the-ipsilateral-somatosensory-cortex-during-voluntary-activity
#15
Yuming Lei, Monica A Perez
An important principle in the organization of the somatosensory cortex is that it processes afferent information from the contralateral side of the body. The role of the ipsilateral somatosensory cortex (iS1) in sensory gating in humans remains largely unknown. Using electroencephalographic recordings over the iS1 and electrical stimulation of the ulnar nerve at the wrist we examined somatosensory evoked potentials (SSEPs; P14/N20, N20/P25, and P25/N33 components) and paired-pulse SSEPs between (interhemispheric inhibition) and within (intracortical inhibition) the iS1 at rest and during tonic index finger voluntary activity...
May 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28513083/screen-printed-ambulatory-electrode-set-enables-accurate-diagnostics-of-sleep-bruxism
#16
Tomi Miettinen, Katja Myllymaa, Anu Muraja-Murro, Susanna Westeren-Punnonen, Taina Hukkanen, Juha Töyräs, Reijo Lappalainen, Esa Mervaala, Kirsi Sipilä, Sami Myllymaa
Currently, definite diagnosis of sleep bruxism requires polysomnography. However, it is restrictedly available, and too cumbersome and expensive for the purpose. The aim of this study was to introduce an ambulatory electrode set and evaluate its feasibility for more cost-effective diagnostics of sleep bruxism. Six self-assessed bruxers (one male, five females; aged 21-58 years) and six healthy controls (four males, two females, aged 21-25 years) underwent a standard polysomnographic study and a concurrent study with the ambulatory electrode set...
May 17, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28513054/is-there-a-common-motor-dysregulation-in-sleepwalking-and-rem-sleep-behaviour-disorder
#17
Mehdi Haridi, Sebastian Weyn Banningh, Marion Clé, Smaranda Leu-Semenescu, Marie Vidailhet, Isabelle Arnulf
This study sought to determine if there is any overlap between the two major non-rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings...
May 17, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28511630/corpus-callosotomy-for-intractable-epilepsy-revisited-the-children-s-hospital-of-michigan-series
#18
Aimee F Luat, Eishi Asano, Ajay Kumar, Harry T Chugani, Sandeep Sood
Corpus callosotomy is a palliative procedure performed to reduce the severity of drug-resistant epilepsy. The authors assessed its efficacy on different seizure types in 20 subjects (age range 5-19 years); 8 with active vagus nerve stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had anterior 2/3 followed later by complete callosotomy. Ten had endoscopic approach. In all, 65% had ≥ 50% reduction of generalized seizures leading to falls (atonic, tonic, myoclonic); 35% became seizure-free (follow-up period: 6 months to 9 years; mean 3 years)...
June 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28510066/the-delta-opioid-receptor-in-pain-control
#19
Khaled Abdallah, Louis Gendron
Nowadays, the delta opioid receptor (DOPr) represents a promising target for the treatment of chronic pain and emotional disorders. Despite the fact that they produce limited antinociceptive effects in healthy animals and in most acute pain models, DOPr agonists have shown efficacy in various chronic pain models. In this chapter, we review the progresses that have been made over the last decades in understanding the role played by DOPr in the control of pain. More specifically, the distribution of DOPr within the central nervous system and along pain pathways is presented...
May 17, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28509118/anti-glomerular-basement-membrane-disease-accompanied-by-systemic-lupus-erythematosus-presenting-central-nervous-system-involvement
#20
Hirohito Sugawara, Hideki Takizawa, Yoshinosuke Shimamura, Norihito Moniwa, Koichi Hasegawa, Yayoi Ogawa
We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (GBM) disease accompanied by systemic lupus erythematosus (SLE) presenting central nervous system involvement in a 32-year-old Japanese male. He was admitted to our hospital because of a 3-week history of fever and rapidly failing renal function requiring hemodialysis (HD). Laboratory tests showed anti-GBM antibody elevation with a value of 16,385 units/ml. On day 85, he had generalized tonic-clonic seizure...
May 2017: CEN Case Reports
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