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https://www.readbyqxmd.com/read/28447323/observation-of-clinically-relevant-drug-interaction-in-chimeric-mice-with-humanized-livers-the-case-of-valproic-acid-and-carbapenem-antibiotics
#1
Eiko Suzuki, Kumiko Koyama, Daisuke Nakai, Ryoya Goda, Hiroshi Kuga, Kan Chiba
BACKGROUND AND OBJECTIVE: Human in vitro and dog in vitro/in vivo researches indicate that the drug-drug interaction (DDI) of decreased plasma valproic acid (VPA) concentration by co-administration of carbapenem antibiotics is caused by inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G) hydrolysis by carbapenems. In this study, we investigated VPA disposition and APEH activities in TK-NOG chimeric mice, whose livers were highly replaced with human hepatocytes, to evaluate the utility of this animal model and the clinical relevance of the DDI mechanism...
April 26, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28446224/immunosuppressive-capacity-of-mesenchymal-stem-cells-correlates-with-metabolic-activity-and-can-be-enhanced-by-valproic-acid
#2
Madeleine C Killer, Philipp Nold, Katharina Henkenius, Lea Fritz, Tabea Riedlinger, Christina Barckhausen, Miriam Frech, Holger Hackstein, Andreas Neubauer, Cornelia Brendel
BACKGROUND: Mesenchymal stem cells (MSCs) have entered the clinic as an Advanced Therapy Medicinal Product and are currently evaluated in a wide range of studies for tissue regeneration or in autoimmune disorders. Various efforts have been made to standardize and optimize expansion and manufacturing processes, but until now reliable potency assays for the final MSC product are lacking. Because recent findings suggest superior therapeutic efficacy of freshly administered MSCs in comparison with frozen cells, we sought to correlate the T-cell suppressive capacity of MSCs with their metabolic activity...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446180/physical-activity-when-riding-an-electric-assisted-bicycle
#3
Sveinung Berntsen, Lena Malnes, Aleksander Langåker, Elling Bere
BACKGROUND: The objectives of the present study were to compare time spent cycling, exercise intensity, and time spent in moderate- (MPA) and vigorous intensity physical activity (VPA) when cycling on an E-bike and a conventional bicycle on two "cycling-to-work" routes with differences in topography, defined as a hilly and a flat route. METHODS: Eight adults (23-54 years, two women) cycled outdoors on a conventional bicycle and an E-bike, on a flat (8.2 km) and a hilly (7...
April 26, 2017: International Journal of Behavioral Nutrition and Physical Activity
https://www.readbyqxmd.com/read/28445602/identification-of-a-novel-mirna-that-increases-transient-protein-expression-in-combination-with-valproic-acid
#4
Hermann-Josef Meyer, Dorothea Reilly, Scott E Martin, Athena W Wong
Transient gene expression in mammalian cells is an efficient process to produce recombinant proteins for various research applications and large molecule therapeutics development. For the first time, we report a screen to identify human microRNAs (miRNAs) that increase titers after polyethylenimine (PEI) mediated transient transfection of a HEK293 cell line. From a library of 875 miRNAs, we identified 2 miRNAs, miR-26a-5p and miR-337-5p, that increased human IgG1 (huIgG1) yields by 50% and 25%, respectively...
April 26, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28441341/a-long-term-treatment-with-arachidonyl-2-chloroethylamide-combined-with-valproate-increases-neurogenesis-in-a-mouse-pilocarpine-model-of-epilepsy
#5
Marta Andres-Mach, Mirosław Zagaja, Agnieszka Haratym-Maj, Radosław Rola, Maciej Maj, Joanna Haratym, Monika Dudra-Jastrzębska, Jarogniew J Łuszczki
Rational polytherapy in the treatment of refractory epilepsy has been the main therapeutic modality for several years. In treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected based on their high anticonvulsant properties, minimal side effects, and impact on the formation of new neurons. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28438715/impact-of-physical-exercise-on-visceral-adipose-tissue-fatty-acid-profile-and-inflammation-in-response-to-a-high-fat-diet-regimen
#6
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Inês O Gonçalves, Ana Moreira, Elisabete Maciel, Sónia Santos, Maria R Domingues, Gema Frühbeck, António Ascensão, José Magalhães
PURPOSE: Studies associate specific fatty-acids (FA) with the pathophysiology of inflammation. We aimed to analyze the impact of exercise on adipose tissue FA profile in response to a high-fat diet (HFD) and to ascertain whether these exercise-induced changes in specific FA have repercussions on obesity-related inflammation. METHODS: Sprague-Dawley rats were assigned into sedentary, voluntary physical-activity (VPA) and endurance training (ET) groups fed a standard (S, 35kcal% fat) or high-fat (71kcal% fat) diets...
April 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28437285/monitoring-protein-unbound-valproic-acid-serum-concentrations-in-clinical-practice
#7
Eveline Wallenburg, Bas Klok, Karin de Jong, Monique de Maat, Nielka van Erp, Sonja Stalpers-Konijnenburg, Guus Essink, Matthijs van Luin
BACKGROUND: Valproic acid (VPA) is an effective anti-epileptic drug and mood stabilizer. A key characteristic of VPA is its high and saturable protein binding at higher concentrations. While the unbound concentration of VPA is responsible for its pharmacological activity, total drug concentrations are monitored in routine clinical practice. Therapeutic drug monitoring (TDM) of unbound VPA is recommended for specific clinical situations. The goal of this study was to evaluate TDM requests for unbound VPA in clinical practice...
April 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28436001/gait-instability-in-valproate-treated-patients-call-to-measure-ammonia-levels
#8
S Kipervasser, C E Elger, A D Korczyn, R D Nass, C M Quesada, M Y Neufeld
OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery...
April 23, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28434161/can-valproic-acid-regulate-neurogenesis-from-nestin-cells-in-the-adult-midbrain
#9
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) causes the motor symptoms (e.g. tremor, muscle rigidity, bradykinesia, postural instability) of Parkinson's disease (PD). It is generally agreed that replacing these neurons will provide better motor symptom relief and fewer side effects than current pharmacotherapies. One potential approach to this is up-regulating endogenous DA neurogenesis in SNc. In the present study, we conducted bioinformatics analyses to identify signalling pathways that control expression of Pax6 and Msx1 genes, which have been identified as potentially important neurogenic regulators in the adult midbrain...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28432707/suberoylanilide-hydroxamic-acid-a-novel-histone-deacetylase-inhibitor-improves-the-development-and-acetylation-level-of-miniature-porcine-handmade-cloning-embryos
#10
J M Sun, K Q Cui, Z P Li, X R Lu, Z F Xu, Q Y Liu, B Huang, D S Shi
Histone deacetylase inhibitors (HDACis) can change the histone acetylation and significantly enhance the developmental competence of the pre-implantation SCNT embryo. To select a proper histone deacetylase inhibitor to improve the success rate and potentially developmental ability of handmade cloning (HMC) embryos of miniature porcine, we compared the effect of two histone deacetylase inhibitors (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the expression level of relevant genes...
April 22, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28427452/modeling-environmental-risk-factors-of-autism-in-mice-induces-ibd-related-gut-microbial-dysbiosis-and-hyperserotonemia
#11
Joon Seo Lim, Mi Young Lim, Yongbin Choi, GwangPyo Ko
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD...
April 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28422609/isotemporal-analysis-of-the-association-of-objectively-measured-physical-activity-with-depressive-symptoms-results-from-hispanic-community-health-study-study-of-latinos-hchs-sol
#12
Chad D Rethorst, Ashley E Moncrieft, Marc D Gellman, Elva M Arredondo, Christina Buelna, Shelia F Castañeda, Martha L Daviglus, Unab I Khan, Krista M Perreira, Daniela Sotres-Alvarez, Mark Stoutenberg
BACKGROUND: The burden of depression among Hispanics/Latinos indicates the need to identify factors related to depressive symptoms. This paper examines the relationship of physical activity (PA) and sedentary behavior (SB) with depressive symptoms in Hispanic/Latinos. METHODS: The Hispanic Community Health Study / Study of Latinos (HCHS/SOL) is a population-based, cohort study of Hispanic/Latinos in four United States metropolitan areas. Objectively measured PA was coded into: sedentary behavior (SB), light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity (VPA); and the Center for Epidemiological Studies Depression Scale-10 assessed depressive symptoms...
April 19, 2017: Journal of Physical Activity & Health
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#13
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#14
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28416782/assessment-of-atherosclerotic-risk-among-patients-with-epilepsy-on-valproic-acid-lamotrigine-and-carbamazepine-treatment
#15
Nudrat A Zuberi, Mukhtiar Baig, Shazia Bano, Zehra Batool, Saeeda Haider, Tahira Perveen
OBJECTIVE: To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk. METHODS: The present cross-sectional study was carried out at the Department of Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from 2012 to 2013. We selected 120 adult patients with epilepsy and 40 control subjects. The patients with epilepsy were divided into 3 groups according to the use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40)...
April 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/28413671/paraneoplastic-limbic-encephalitis-in-a-patient-with-extensive-disease-small-cell-lung-cancer
#16
Sebastian Ochenduszko, Bartosz Wilk, Joanna Dabrowska, Izabela Herman-Sucharska, Anna Dubis, Miroslawa Puskulluoglu
Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently accompanying malignancy, coexisting in ~50% of the cases with small-cell lung cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated, with production of specific anti-Hu antibodies and activation of T-cells directed against onconeural antigens present on both tumor cells and neurons. We herein report the case of a 50-year-old male patient who, prior to being diagnosed with SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive dysfunction with severe memory impairment, anxiety and hallucinations)...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28411969/valproate-induced-hyperammonemic-encephalopathy-in-general-hospital-patients-with-one-or-more-psychiatric-disorders
#17
Chandani Lewis, George E Tesar, Roman Dale
BACKGROUND: Divalproex sodium/valproic acid (VPA) is an antiepileptic drug approved for use in epilepsy and bipolar disorder. Valproate-induced hyperammonemia occurs in up to 50% of VPA-treated patients, some of whom may become encephalopathic. Valproate-induced hyperammonemic encephalopathy (VHE) is thought to be rare, and for a variety of reasons, the diagnosis requires a high index of suspicion. OBJECTIVE: The study's goals are to determine how common VHE is, and the quality of treatment provided when diagnosed...
February 24, 2017: Psychosomatics
https://www.readbyqxmd.com/read/28408298/antidepressant-like-effect-of-valproic-acid-possible-involvement-of-pi3k-akt-mtor-pathway
#18
Isabel Vieira de Assis Lima, Ana Flávia Almeida-Santos, Talita Hélen Ferreira-Vieira, Daniele Cristina Aguiar, Fabíola Mara Ribeiro, Alline Cristina de Campos, Antônio Carlos Pinheiro de Oliveira
RATIONALE: Few studies suggest that antidepressants exert their effects by activating some signaling pathways, including the phosphatidylinositol 3-kinase (PI3K). Moreover, valproic acid (VPA) activates the PI3K pathway. Thus, here we investigated the antidepressant-like effect of VPA and if its effect is related to PI3K/Akt/mTOR activation. METHODS: C57Bl/6 (WT) and PI3Kγ(-/-) mice received VPA injections (30, 100 or 300mg/kg, i.p.) and 30minutes after they were submitted to the forced swimming (FS), tail suspension (TS) and open field (OF) tests...
April 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28408291/altered-expression-of-circadian-rhythm-and-extracellular-matrix-genes-in-the-medial-prefrontal-cortex-of-a-valproic-acid-rat-model-of-autism
#19
Nikkie F M Olde Loohuis, Gerard J M Martens, Hans van Bokhoven, Barry B Kaplan, Judith R Homberg, Armaz Aschrafi
Autism spectrum disorders (ASD) are a highly heterogeneous group of neurodevelopmental disorders caused by complex interplay between various genes and environmental factors during embryonic development. Changes at the molecular, cellular and neuroanatomical levels are especially evident in the medial prefrontal cortex (mPFC) of ASD patients and are particularly contributing to social impairments. In the present study we tested the hypothesis that altered neuronal development and plasticity, as seen in the mPFC of ASD individuals, may result from aberrant expression of functionally connected genes...
April 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28407839/-effect-of-histone-acetylation-deacetylation-imbalances-on-key-gene-of-planar-cell-polarity-pathway
#20
Hong-Yu Duan, Yi Zhang, Kai-Yu Zhou, Chuan Wang, DA-Jian Qiu, Yi-Min Hua
OBJECTIVE: To investigate the effect of histone acetylation/deacetylation imbalances on embryonic hearts of mice and its effect on key genes of planar cell polarity (PCP) pathway-Vangl2, Scrib and Rac1 in H9C2 cells. METHODS: Forty pregnant C57/B6 mice were randomly assigned into three groups: blank group (n=10), vehicle group (n=10), and valproic acid (VPA)-treated group (n=20). In the VPA-treated group, VPA, a histone deacetylase (HDAC) inhibitor, was administered to each individual dam intraperitoneally at a single dose of 700 mg/kg on embryonic day 10...
April 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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