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Maja Johansson, Maria Månsson, Lars-Eric Lins, Bruce Scharschmidt, Magnus Doverskog, Torbjörn Bäckström
RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans. METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs...
February 28, 2018: Psychopharmacology
Kohei Kawakami, Kazuo Yamada, Takaya Yamada, Toru Nabika, Masato Nomura
'Haiibuki' is a giant embryo rice cultivar that contains abundant γ-aminobutyric acid (GABA) compared with conventional rice cultivars. Here, we performed a functional evaluation of 'GABA-enriched brown rice' (GEBR) prepared by modifying the 'Haiibuki' cultivar to contain more GABA. Study 1: Spontaneously hypertensive rats were divided into three groups [control (cornstarch), normal brown rice, and GEBR] and fed an orally administered diet for 4 wk. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group as compared with the other groups...
2018: Journal of Nutritional Science and Vitaminology
Peter Good
Because certain hereditary diseases show autistic behavior, and autism often runs in families, researchers seek genes underlying the pathophysiology of autism, thus core behaviors. Other researchers argue environmental factors are decisive, citing compelling evidence of an autism epidemic in the United States beginning about 1980. Recognition that environmental factors influence gene expression led to synthesis of these views - an 'epigenetic epidemic' provoked by pervasive environmental agents altering expression of vulnerable genes, inducing characteristic autistic biochemistries in many mothers and infants...
February 2018: Clinical Nutrition ESPEN
Katy Vincent, Andrew Baranowski, Siladitya Bhattacharya, Judy Birch, Ying Cheong, Roman Cregg, Jane Daniels, Catherine A Hewitt, Gary J Macfarlane, Lee Middleton, Wojciech Szubert, Irene Tracey, Amanda C de C Williams, Andrew W Horne
INTRODUCTION: Chronic pelvic pain (CPP) affects more than 1 million UK women with associated healthcare costs of £158 million annually. Current evidence supporting interventions when no underlying pathology is identified is very limited and treatment is frequently inadequate. Gabapentin (a GABA analogue) is efficacious and often well tolerated in other chronic pain conditions. We have completed a successful pilot randomised controlled trial Gabapentin for Pelvic Pain 1 (GaPP1) and here describe the protocol for our definitive multicentre trial to assess the efficacy of gabapentin in the management of CPP in women Gabapentin for Pelvic Pain 2 (GaPP2)...
January 31, 2018: BMJ Open
Yi Zhang, Yajun Lian, Nanchang Xie
RATIONALE: Early onset epileptic encephalopathy (EOEE) is one of the most serious early onset epilepsies. The etiopathology of this condition remains unclear, and recent evidence indicated that gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 (GABRB3) gene mutations might be associated with EOEE. Furthermore, the therapeutic regimen for EOEE has yet to be well elucidated. Herein, we reported the clinical and genetic features of a case with GABRB3-related EOEE. PATIENT CONCERNS: A 6-year-old girl developed epileptic seizures 3 days after birth...
December 2017: Medicine (Baltimore)
Zubia Begum, Ishrat Younus
The current study was designed with the aim to investigate anti-anxiety potential of Hibiscus rosa sinensis roots and its possible mechanism of action. For this purpose hole board test, elevated plus maze test and light/dark exploration test were employed. The ethanol extract of plant was administered orally at two different doses i.e. 100 and 500 mg/kg for consecutive 14 days. The results of present investigation indicate that plant extract significantly (p < 0.05) increased the number of head dips and rearings as compared to control on respective days of observation...
January 25, 2018: Metabolic Brain Disease
André L Teixeira, Plinio Santos Ramos, Milena Samora, Jeann L Sabino-Carvalho, Djalma Rabelo Ricardo, Eduardo Colombari, Lauro C Vianna
Previous studies indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. Based on previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset is primarily mediated by muscle mechanoreceptors afferents. Therefore, in this study we sought to determine if central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Eman Abd-Elrasheed, Sara Nageeb El-Helaly, Manal M El-Ashmoony, Salwa Salah
Intranasal Zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 23full factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied...
December 13, 2017: Drug Development and Industrial Pharmacy
Anna Leonte, Lorenza S Colzato, Laura Steenbergen, Bernhard Hommel, Elkan G Akyürek
In a randomized, double-blind, and placebo-controlled experiment, the acute effects of gamma-aminobutyric acid (GABA) supplementation on temporal and spatial attention in young healthy adults were investigated. A hybrid two-target rapid serial visual presentation task was used to measure temporal attention and integration. Additionally, a visual search task was used to measure the speed and accuracy of spatial attention. While temporal attention depends primarily on the distribution of limited attentional resources across time, spatial attention represents the engagement and disengagement by relevant and irrelevant stimuli across the visual field...
February 2018: Brain and Cognition
Hee-Eun Kim, Baek-Il Kim
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Establishment of a new marginal plaque index with high sensitivity for changes in oral hygiene. Deinzer R, Jahns S, Harnacke D. J Periodontol 2014; 85(12):1730-8. SOURCE OF FUNDING: The study was supported by a sponsorship from GABA International, Therwil, Switzerland. TYPE OF STUDY/DESIGN: Observational case-control study.
December 2017: Journal of Evidence-based Dental Practice
Eman Abd-Elrasheed, Sara Nageeb El-Helaly, Manal M El-Ashmoony, Salwa Salah
BACKGROUND: Zaleplon is a pyrazolopyrimidin derivative hypnotic drug indicated for the short-term management of insomnia. Zaleplon belongs to Class II drugs, according to the biopharmaceutical classification system (BCS), showing poor solubility and high permeability. It undergoes extensive first-pass hepatic metabolism after oral absorption, with only 30% of Zaleplon being systemically available. It is available in tablet form which is unable to overcome the previous problems. OBJECTIVE: The aim of this study is to enhance solubility and bioavailability via utilizing nanotechnology in the formulation of intranasal Zaleplon nano-emulsion (ZP-NE) to bypass the barriers and deliver an effective therapy to the brain...
November 30, 2017: Current Drug Delivery
Camilo de la Fuente-Sandoval, Francisco Reyes-Madrigal, Xiangling Mao, Pablo León-Ortiz, Oscar Rodríguez-Mayoral, Helgi Jung-Cook, Rodolfo Solís-Vivanco, Ariel Graff-Guerrero, Dikoma C Shungu
BACKGROUND: Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. METHODS: Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study...
October 10, 2017: Biological Psychiatry
Yibin Zhu, Rudian Zhang, Bei Zhang, Tongyan Zhao, Penghua Wang, Guodong Liang, Gong Cheng
Mosquitoes are hematophagous insects that carry-on and transmit many human viruses. However, little information is available regarding the common mechanisms underlying the infection of mosquitoes by these viruses. In this study, we reveal that the hematophagous nature of mosquitoes contributes to arboviral infection after a blood meal, which suppresses antiviral innate immunity by activating the GABAergic pathway. dsRNA-mediated interruption of the GABA signaling and blockage of the GABAA receptor by the specific inhibitors both significantly impaired arbovirus replication...
November 2, 2017: Nature Communications
Jae Hyeon Yoo, Tae-Woo Ha, Jin Tae Hong, Ki-Wan Oh
Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice...
November 1, 2017: Biomolecules & Therapeutics
Haofeng Li, Jingcheng Xiao, Xinuo Li, Huimin Chen, Dian Kang, Yuhao Shao, Boyu Shen, Zhangpei Zhu, Xiaoxi Yin, Lin Xie, Guangji Wang, Yan Liang
A bidirectional route of communication between the gastrointestinal tract and the central nervous system, termed the "gut-brain axis", is becoming increasingly relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is extremely popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although their plasma and cerebral exposure levels were extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown. In the present study, the neuroprotective effects of PNE are systematically studied via investigating the regulation of PNE on gastrointestinal microbial community and gamma aminobutyric acid (GABA) receptors...
October 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Ludovico Mineo, Carmen Concerto, Dhaval Patel, Tyrone Mayorga, Michael Paula, Eileen Chusid, Eugenio Aguglia, Fortunato Battaglia
BACKGROUND: Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS)...
October 17, 2017: Neuropsychobiology
Manar A Nader, Hayam Ateyya, Mohamed El-Shafey, Nagla A El-Sherbeeny
The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination...
October 11, 2017: Neurochemistry International
Y Zhang, K Wang, L Arendt-Nielsen, B E Cairns
BACKGROUND: In burning mouth patients, analgesia after oral administration of clonazepam may result from modulation of peripheral γ-aminobutyric acid (GABA) receptors. METHODS: The effect of oral administration of test solutions (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated for the amelioration of pain and sensitivity induced by application of capsaicin (1%, 2 min) to the tongue of thirty healthy male and female subjects in this four-session, randomized, placebo-controlled, double-blinded, cross-over study...
October 11, 2017: European Journal of Pain: EJP
Jide Tian, Hoa Dang, Angela Hu, Willem Xu, Daniel L Kaufman
The activation of β-cell's A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS). Lesogaberan (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD) that appears to be safe for human use...
2017: Journal of Diabetes Research
B Gómez-Giménez, V Felipo, A Cabrera-Pastor, A Agustí, V Hernández-Rabaza, M Llansola
It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin)...
October 3, 2017: Neurotoxicity Research
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