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https://www.readbyqxmd.com/read/28741622/in-vivo-detection-of-cpp-115-target-engagement-in-human-brain
#1
Andrew P Prescot, Steven R Miller, Gary Ingenito, Rebekah S Huber, Douglas G Kondo, Perry F Renshaw
CPP-115, a next-generation γ-amino butyric acid (GABA)-aminotransferase (AT) inhibitor, shows comparable pharmacokinetics, improved safety and tolerability, and a more favorable toxicity profile when compared to vigabatrin. The pharmacodynamic characteristics of CPP-115 remain to be evaluated. The present study employed state-of-the-art proton magnetic resonance spectroscopy techniques to measure changes in brain GABA+ (the composite resonance of GABA, homocarnosine, and macromolecules) concentrations in healthy subjects receiving oral daily doses of CPP-115 or placebo...
July 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28596511/effect-of-alprazolam-on-redox-status-in-renal-transplantation-donors-and-recipients
#2
Meltem Güner Can, Özgen Ilgaz Koçyiğit, Uğur Aksu, Ali Özer, Fevzi Toraman
BACKGROUND Benzodiazepines are the most popular premedication drugs thought to act through the GABA/benzodiazepine receptor complex and alprazolam is one of the most potent benzodiazepines that have a quick onset. While there is a growing body of evidence supporting alprazolam in the amelioration of redox status in animals, no study has been performed concerning its antioxidant activity in humans. The purpose of this investigation was to determine the effect of alprazolam on redox status. MATERIAL AND METHODS This study was a four-group randomized controlled trial...
June 9, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28485217/gaba-promotes-elastin-synthesis-and-elastin-fiber-formation-in-normal-human-dermal-fibroblasts-hdfs
#3
Eriko Uehara, Hideki Hokazono, Mariko Hida, Takako Sasaki, Hidekatsu Yoshioka, Noritaka Matsuo
The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner...
June 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28456544/gastroprotective-effect-of-gamma-aminobutyric-acid-against-ethanol-induced-gastric-mucosal-injury
#4
Min Xie, Haihong Chen, Shaoping Nie, Wei Tong, Junyi Yin, Mingyong Xie
The present study aimed to investigate the gastroprotective effect of gamma-aminobutyric acid (GABA) on ethanol-induced gastric mucosal injury and gastric epithelial cells injury. Rats were divided into the control group, vehicle group and GABA-treated groups (10, 20 and 40 mg/kg/day). After GABA ingestion for 14 days, rats except the control group were given 1 mL pure ethanol by oral gavage in order to induce acute gastric mucosal lesion. The human gastric epithelial cell line GES-1 was incubated with GABA (100, 200 and 400 μM) for 24 h, followed by treatment with 8% ethanol for 3 h to induce cell injury...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28418172/analgesic-effect-of-clobazam-in-chronic-low-back-pain-but-not-in-experimentally-induced-pain
#5
J Schliessbach, P H Vuilleumier, A Siegenthaler, L Bütikofer, A Limacher, P Juni, H U Zeilhofer, L Arendt-Nielsen, M Curatolo
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests...
April 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27927951/effects-of-the-selective-%C3%AE-5-gabaar-antagonist-s44819-on-excitability-in-the-human-brain-a-tms-emg-and-tms-eeg-phase-i-study
#6
RANDOMIZED CONTROLLED TRIAL
Ghazaleh Darmani, Carl M Zipser, Gabriele M Böhmer, Karine Deschet, Florian Müller-Dahlhaus, Paolo Belardinelli, Matthias Schwab, Ulf Ziemann
Alpha-5 gamma-aminobutyric acid type A receptors (α5-GABAARs) are located extrasynaptically, regulate neuronal excitability through tonic inhibition, and are fundamentally important for processes such as plasticity and learning. For example, pharmacological blockade of α5-GABAAR in mice with ischemic stroke improved recovery of function by normalizing exaggerated perilesional α5-GABAAR-dependent tonic inhibition. S44819 is a novel competitive selective antagonist of the α5-GABAAR at the GABA-binding site...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27548190/acceptability-safety-and-efficacy-of-oral-administration-of-extracts-of-black-or-red-maca-lepidium-meyenii-in-adult-human-subjects-a-randomized-double-blind-placebo-controlled-study
#7
Carla Gonzales-Arimborgo, Irma Yupanqui, Elsa Montero, Dulce E Alarcón-Yaquetto, Alisson Zevallos-Concha, Lidia Caballero, Manuel Gasco, Jianping Zhao, Ikhlas A Khan, Gustavo F Gonzales
The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels...
August 18, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27247854/exogenous-dopamine-reduces-gaba-receptor-availability-in-the-human-brain
#8
Hans C Lou, Astrid Rosenstand, David J Brooks, Dirk Bender, Steen Jakobsen, Jakob U Blicher, Kim V Hansen, Arne Møller
BACKGROUND: While it has recently been shown that dopamine release stimulates conscious self-monitoring through the generation of gamma oscillations in medial prefrontal/anterior cingulate cortex, and that the GABAergic system is effective in producing such oscillations, interaction of the two transmitter systems has not been demonstrated in humans. We here hypothesize that dopamine challenge stimulates the GABA system directly in the medial prefrontal/anterior cingulate region in the human brain...
July 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27222045/proliferative-effects-of-gamma-amino-butyric-acid-on-oral-squamous-cell-carcinoma-cells-are-associated-with-mitogen-activated-protein-kinase-signaling-pathways
#9
Jing Ma, Yan Zhang, Jun Wang, Tianyu Zhao, Ping Ji, Jinlin Song, Hongmei Zhang, Wenping Luo
Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system, has been reported to play an important physiological role in peripheral non-neuronal tissues, such as tumors. However, whether deregulated GABA is associated with oral squamous cell carcinoma (OSCC) is currently unknown. In this study, we investigated the effects of GABA on the proliferation of the OSCC cell line, Tca8113. Immunohistochemical analyses were performed to examine the expression of GABA A type receptor pi subunit (GABRP) in human OSCC tissues, and reverse transcription polymerase chain reaction, immunofluorescence staining and western blot analysis were performed to examine the expression of GABRP in Tca8113 cells...
July 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27062388/carnosine-and-anserine-homeostasis-in-skeletal-muscle-and-heart-is-controlled-by-%C3%AE-alanine-transamination
#10
Laura Blancquaert, Shahid P Baba, Sebastian Kwiatkowski, Jan Stautemas, Sanne Stegen, Silvia Barbaresi, Weiliang Chung, Adjoa A Boakye, J David Hoetker, Aruni Bhatnagar, Joris Delanghe, Bert Vanheel, Maria Veiga-da-Cunha, Wim Derave, Inge Everaert
KEY POINTS: Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β-alanine, which is in turn controlled by degradation of β-alanine in liver and kidney...
September 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27028535/ketamine-a-review-of-clinical-pharmacokinetics-and-pharmacodynamics-in-anesthesia-and-pain-therapy
#11
REVIEW
Marko A Peltoniemi, Nora M Hagelberg, Klaus T Olkkola, Teijo I Saari
Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers. It undergoes oxidative metabolism, mainly to norketamine by cytochrome P450 (CYP) 3A and CYP2B6 enzymes. The use of S-ketamine is increasing worldwide, since the S(+)-enantiomer has been postulated to be a four times more potent anesthetic and analgesic than the R(-)-enantiomer and approximately two times more effective than the racemic mixture of ketamine...
September 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/26450608/probiotic-attributes-antioxidant-anti-inflammatory-and-neuromodulatory-effects-of-enterococcus-faecium-cfr-3003-in-vitro-and-in-vivo-evidence
#12
G Divyashri, G Krishna, Muralidhara, S G Prapulla
Accumulating evidence suggests that probiotic bacteria play a vital role in modulating various aspects integral to the health and well-being of humans. In the present study, probiotic attributes and the antioxidant, anti-inflammatory and neuromodulatory potential of Enterococcus faecium CFR 3003 were investigated by employing suitable model systems. E. faecium exhibited robust resistance to gastrointestinal stress conditions as it could withstand acid stress at pH 1.5, 2 and 3. The bacterium also survived at a bile salt concentration of 0...
December 2015: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/26226414/immunological-gabaergic-interactions-and-therapeutic-applications-in-autoimmune-diseases
#13
REVIEW
Gérald J Prud'homme, Yelena Glinka, Qinghua Wang
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. However, it is also produced in other sites; notably by pancreatic β cells and immune cells. The function of GABA in the immune system is at an early stage of study, but it exerts inhibitory effects that are relevant to autoimmune diseases. The study of GABAergic interactions in the immune system has centered on three main aspects: 1) the expression of GABA and the relevant GABAergic molecular machinery; 2) the in vitro response of immune cells; and 3) therapeutic applications in autoimmune diseases...
November 2015: Autoimmunity Reviews
https://www.readbyqxmd.com/read/26052150/the-improvement-of-sleep-by-oral-intake-of-gaba-and-apocynum-venetum-leaf-extract
#14
Atsushi Yamatsu, Yusuke Yamashita, Isafumi Maru, Jinwei Yang, Jin Tatsuzaki, Mujo Kim
The effects of two food materials, γ-aminobutyric acid (GABA) produced by natural fermentation and Apocynum venetum leaf extract (AVLE), on the improvement of sleep were investigated in humans. The electroencephalogram (EEG) test revealed that oral administration of GABA (100 mg) and AVLE (50 mg) had beneficial effects on sleep. GABA shortened sleep latency by 5.3 min and AVLE increased non-rapid eye movement (REM) sleep time by 7.6%. Simultaneous intake of GABA and AVLE shortened sleep latency by 4.3 min and increased non-REM sleep time by 5...
2015: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/26028828/maxillofacial-injuries-due-to-animal-bites
#15
REVIEW
Shruti Chhabra, Naveen Chhabra, Shivani Gaba
INTRODUCTION: Animal bites are a significant public health problem, with the majority of bites coming from dogs, cats and humans. These may present as punctures, abrasions, tears, or avulsions. The force and relative bluntness of the teeth also increases the possibility of a crush injury with devitalized tissue .The clinical presentation and appropriate treatment of infected bite wounds vary according to the animal and causative organisms. These wounds have always been considered complex injuries contaminated with a unique polymicrobial inoculum...
June 2015: Journal of Maxillofacial and Oral Surgery
https://www.readbyqxmd.com/read/25892751/review-article-health-benefits-of-some-physiologically-active-ingredients-and-their-suitability-as-yoghurt-fortifiers
#16
REVIEW
A E Fayed
The article is concerned with health benefits of two main physiologically active ingredients namely, Isoflavones and γ-Aminobutyric acid, with emphasis on their fitness for fortification of yoghurt to be consumed as a functional food. Isoflavones (ISO) are part of the diphenol compounds, called "phytoestrogens," which are structurally and functionally similar to estradiol, the human estrogen, but much less potent. Because of this similarity, ISO were suggested to have preventive effects for many kinds of hormone-dependent diseases...
May 2015: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/25835611/-borneol-alleviates-mechanical-hyperalgesia-in-models-of-chronic-inflammatory-and-neuropathic-pain-in-mice
#17
Jun Jiang, Ying Ying Shen, Jun Li, Yu Hui Lin, Chun Xia Luo, Dong Ya Zhu
Chronic pain is a major public health problem categorized as inflammatory or neuropathic, each involving impaired GABAergic control in the spinal cord of mammals. (+)-Borneol, a bicyclic monoterpene present in the essential oil of plants, is used for analgesia and anesthesia in traditional Chinese medicine. It has been reported that (+)-borneol directly potentiates GABA activity at recombinant human GABAA receptors. Although borneol has antinociceptive effect on acute pain models, little is known about its effect on chronic pain and its mechanism...
June 15, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/25811291/a-bioaccessible-fraction-of-parboiled-germinated-brown-rice-exhibits-a-higher-anti-inflammatory-activity-than-that-of-brown-rice
#18
COMPARATIVE STUDY
Siriporn Tuntipopipat, Chawanphat Muangnoi, Parunya Thiyajai, Warangkana Srichamnong, Somsri Charoenkiatkul, Kemika Praengam
Parboiled germinated brown rice (PGBR) has been suggested as a functional food because it is relatively rich in a number of nutrients and health promoting compounds. Here we compared the bioaccessibility of several of the bioactive compounds in cooked PGBR and brown rice (BR) by simulating oral, gastric and small intestinal digestion. The uptake and retention of bioactive compounds from a bioaccessible fraction also was determined using Caco-2 human intestinal cells. The anti-inflammatory activity of the bioaccessible fraction from digested BR and PGBR was then assessed with Caco-2 cells that were activated with H2O2 + IL-1β...
May 2015: Food & Function
https://www.readbyqxmd.com/read/25742870/%C3%A2-h-and-%C3%A2-%C3%A2-c-nmr-spectroscopy-of-thy-1-appsl-mice-brain-extracts-indicates-metabolic-changes-in-alzheimer-s-disease
#19
A Doert, U Pilatus, F Zanella, W E Müller, G P Eckert
Biochemical alterations underlying the symptoms and pathomechanisms of Alzheimer's disease (AD) are not fully understood. However, alterations of glucose metabolism and mitochondrial dysfunction certainly play an important role. (1)H- and (13)C-NMR spectroscopy exhibits promising results in providing information about those alterations in vivo in patients and animals, especially regarding the mitochondrial tricarboxylic acid (TCA) cycle. Accordingly, transgenic mice expressing mutant human amyloid precursor protein (APP(SL))-serving as a model of neuropathological changes in AD-were examined with in vitro 1D (1)H- and 2D (1)H-(13)C-HSQC-NMR spectroscopy after oral administration of 1-(13)C-glucose and acquisition of brain material after 30 min...
April 2015: Journal of Neural Transmission
https://www.readbyqxmd.com/read/25577325/alterations-of-neurotransmitter-norepinephrine-and-gamma-aminobutyric-acid-correlate-with-murine-behavioral-perturbations-related-to-bisphenol-a-exposure
#20
Hiroshi Ogi, Kyoko Itoh, Hiroshi Ikegaya, Shinji Fushiki
AIM: Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes. METHODS: C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams...
September 2015: Brain & Development
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