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https://www.readbyqxmd.com/read/28238856/gemcitabine-kills-proliferating-endothelial-cells-exclusively-via-acid-sphingomyelinase-activation
#1
Albert J van Hell, Adriana Haimovitz-Friedman, Zvi Fuks, William D Tap, Richard Kolesnick
Gemcitabine is a widely-used anti-cancer drug with a well-defined mechanism of action in normal and transformed epithelial cells. However, its effect on endothelial cells is largely unknown. Acid sphingomyelinase (ASMase) is highly expressed in endothelial cells, converting plasma membrane sphingomyelin to pro-apoptotic ceramide upon activation by diverse stresses. In the current study, we investigated gemcitabine impact in primary cultures of endothelial cells. We find baseline ASMase increases markedly in bovine aortic endothelial cells (BAEC) as they transit from a proliferative to a confluent growth-arrested state...
February 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28237034/machine-learning-and-docking-models-for-mycobacterium-tuberculosis-topoisomerase-i
#2
Sean Ekins, Adwait Anand Godbole, György Kéri, Lászlo Orfi, János Pato, Rajeshwari Subray Bhat, Rinkee Verma, Erin K Bradley, Valakunja Nagaraja
There is a shortage of compounds that are directed towards new targets apart from those targeted by the FDA approved drugs used against Mycobacterium tuberculosis. Topoisomerase I (Mttopo I) is an essential mycobacterial enzyme and a promising target in this regard. However, it suffers from a shortage of known inhibitors. We have previously used computational approaches such as homology modeling and docking to propose 38 FDA approved drugs for testing and identified several active molecules. To follow on from this, we now describe the in vitro testing of a library of 639 compounds...
March 2017: Tuberculosis
https://www.readbyqxmd.com/read/28225710/chronic-stress-exacerbates-neuropathic-pain-via-the-integration-of-stress-affect-related-information-with-nociceptive-information-in-the-central-nucleus-of-the-amygdala
#3
Ming-Jia Li, Ling-Yu Liu, Lin Chen, Jie Cai, You Wan, Guo-Gang Xing
Exacerbation of pain by chronic stress and co-morbidity of pain with stress-related psychiatric disorders including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim (FS) stress-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that chronic FS stress (CFSS) indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats...
December 29, 2016: Pain
https://www.readbyqxmd.com/read/28167465/co-treatment-with-imipramine-averted-haloperidol-instigated-tardive-dyskinesia-association-with-serotonin-in-brain-regions
#4
Noreen Samad, Farzana Yasmin, Darakhshan Jabeen Haleem
Outcome of imipramine (IMI) treatment was scrutinized on progression of haloperidol instigated tardive dyskinesia (TD). 0.2 mg/kg/rat dosage of haloperidol provided orally to rats for 2 weeks enhanced vacuous chewing movements that escalated when the process proceeded for 5 weeks. Following 2 weeks co-injection 5 mg/kg dosage of IMI was diminished haloperidol-instigated VCMs and fully averted following five weeks. The potency of 8-OH-DPAT-instigated locomotor activity exhibited higher in saline+haloperidol treated rats while not observed in IMI+ haloperidol treated rats...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28142101/ionic-liquid-impregnated-agarose-film-two-phase-micro-electrodriven-membrane-extraction-il-af-%C3%AE-eme-for-the-analysis-of-antidepressants-in-water-samples
#5
Nor Suhaila Mohamad Hanapi, Mohd Marsin Sanagi, Abd Khamim Ismail, Wan Aini Wan Ibrahim, Nor'ashikin Saim, Wan Nazihah Wan Ibrahim
The aim of this study was to investigate and apply supported ionic liquid membrane (SILM) in two-phase micro-electrodriven membrane extraction combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for pre-concentration and determination of three selected antidepressant drugs in water samples. A thin agarose film impregnated with 1-hexyl-3-methylimidazolium hexafluorophosphate, [C6MIM] [PF6], was prepared and used as supported ionic liquid membrane between aqueous sample solution and acceptor phase for extraction of imipramine, amitriptyline and chlorpromazine...
January 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28102110/evaluation-of-the-antidepressant-and-anxiolytic-like-effects-of-a-hydrophilic-extract-from-the-green-seaweed-ulva-sp-in-rats
#6
Nicolas Violle, Pascale Rozan, Hervé Demais, Pi Nyvall Collen, Jean-François Bisson
OBJECTIVES: The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans. METHODS: After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST)...
January 19, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28096878/reversion-of-bdnf-akt-and-creb-in-hippocampus-of-chronic-unpredictable-stress-induced-rats-effects-of-phytochemical-bacopa-monnieri
#7
Somoday Hazra, Sourav Kumar, Goutam Kumar Saha, Amal Chandra Mondal
OBJECTIVE: The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. METHODS: We examined the effects of chronic administration of BME on CUS exposed rats for 28 days...
January 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28093219/a-mixed-glucocorticoid-mineralocorticoid-receptor-modulator-dampens-endocrine-and-hippocampal-stress-responsivity-in-male-rats
#8
Elizabeth T Nguyen, Joshua Streicher, Sarah Berman, Jody L Caldwell, Valentina Ghisays, Christina M Estrada, Aynara C Wulsin, Matia B Solomon
Aberrant glucocorticoid secretion is implicated in the pathophysiology of stress-related disorders (i.e., depression, anxiety). Glucocorticoids exert biological effects via mineralocorticoid (MR) and glucocorticoid (GR) receptors. Previous data from our laboratory indicate that GR antagonism/modulation (i.e., mifepristone, CORT 108297) regulate endocrine, behavioral, and central stress responses. Because of the dynamic interplay between MR and GR on HPA axis regulation and emotionality, compounds targeting both receptors are of interest for stress-related pathology...
January 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#9
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28071711/transient-anhedonia-phenotype-and-altered-circadian-timing-of-behaviour-during-night-time-dim-light-exposure-in-per3-mice-but-not-wildtype-mice
#10
Bruno Jacson Martynhak, Alexandra L Hogben, Panos Zanos, Polymnia Georgiou, Roberto Andreatini, Ian Kitchen, Simon N Archer, Malcolm von Schantz, Alexis Bailey, Daan R van der Veen
Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3(-/-) mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3(-/-)) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063625/regulation-of-insulin-receptor-phosphorylation-in-the-brains-of-prenatally-stressed-rats-new-insight-into-the-benefits-of-antidepressant-drug-treatment
#11
Katarzyna Głombik, Joanna Ślusarczyk, Ewa Trojan, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
A growing body of evidence supports the involvement of disturbances in the brain insulin pathway in the pathogenesis of depression. On the other hand, data concerning the impact of antidepressant drug therapy on brain insulin signaling remain scare and insufficient. We determinated the influence of chronic treatment with antidepressant drugs (imipramine, fluoxetine and tianeptine) on the insulin signaling pathway of the brain of adult prenatally stressed rats. 3-month-old prenatally stressed and control rats were treated for 21 days with imipramine, fluoxetine or tianeptine (10mg/kg/day i...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28063309/qualitative-and-quantitative-changes-in-phospholipids-and-proteins-investigated-by-spectroscopic-techniques-in-animal-depression-model
#12
J Depciuch, M Sowa-Kucma, G Nowak, M Papp, P Gruca, P Misztak, M Parlinska-Wojtan
Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum...
December 28, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28012396/antidepressant-like-effects-of-hydrolysable-tannins-of-terminalia-catappa-leaf-extract-via-modulation-of-hippocampal-plasticity-and-regulation-of-monoamine-neurotransmitters-subjected-to-chronic-mild-stress-cms
#13
Y Chandrasekhar, E M Ramya, K Navya, G Phani Kumar, K R Anilakumar
Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28003827/when-the-patient-believes-that-the-organs-are-destroyed-manifestation-of-cotard-s-syndrome
#14
Leonardo Machado, Luiz Evandro de Lima Filho, Liliane Machado
Cotard's Syndrome (CS) is a rare clinical event described for the first time in 1880 by the neurologist and psychiatrist Jules Cotard and characterized by negation delusions (or nihilists). Immortality and hypochondriac delusions are also typical. Nowadays, it is known that CS can be associated with many neuropsychiatric conditions. In this article, we describe the case of a patient that believed not having more organs and having the body deformed and whose CS was associated with a bigger depressive disorder...
2016: Case Reports in Medicine
https://www.readbyqxmd.com/read/27997040/clinical-pharmacogenetics-implementation-consortium-guideline-cpic%C3%A2-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-tricyclic-antidepressants-2016-update
#15
J Kevin Hicks, Katrin Sangkuhl, Jesse J Swen, Vicki L Ellingrod, Daniel J Müller, Kazutaka Shimoda, Jeffrey R Bishop, Evan D Kharasch, Todd C Skaar, Andrea Gaedigk, Henry M Dunnenberger, Teri E Klein, Kelly E Caudle, Julia C Stingl
CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants...
December 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27975170/neuroprotective-effects-of-antidepressants-via-upregulation-of-neurotrophic-factors-in-the-mptp-model-of-parkinson-s-disease
#16
Sina Shadfar, Yu-Gyeong Kim, Nikita Katila, Sabita Neupane, Uttam Ojha, Sunil Bhurtel, Sunil Srivastav, Gil-Saeng Jeong, Pil-Hoon Park, Jin Tae Hong, Dong-Young Choi
Neurotrophic factors are essential for neuronal survival, plasticity, and development and have been implicated in the action mechanism of antidepressants. In this study, we assessed the neurotrophic factor-inducing and neuroprotective properties of antidepressants. In the first part of the study, we found that fluoxetine, imipramine, and milnacipran (i.p., 20 mg/kg/day for 1 week or 3 weeks) upregulated brain-derived neurotrophic factor in the striatum and substantia nigra both at 1 week and 3 weeks. In contrast, an increase in the glial-derived neurotrophic factor was more obvious at 3 weeks after the antidepressants treatment...
December 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27960559/investigational-drugs-for-treating-major-depressive-disorder
#17
Ashish Dhir
Treatment of patients suffering from major depression could be highly challenging for psychiatrists. Intractability as well as relapse is commonly seen among these patients, leading to functional impairment and poor quality of life. The present review discusses some of the novel investigational drugs that are under pre-clinical or clinical phases in the treatment of major depression. Areas covered: Molecules belonging to different classes such as triple reuptake inhibitors, opioid receptors, ionotropic and metabotropic glutamate receptors, and neurotrophin in the treatment of major depression are covered in this article...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27894924/antidepressant-like-effects-exerted-by-the-intranasal-administration-of-a-glucagon-like-peptide-2-derivative-containing-cell-penetrating-peptides-and-a-penetration-accelerating-sequence-in-mice
#18
Sachie Sasaki-Hamada, Ryuji Nakamura, Yusuke Nakao, Toshiki Akimoto, Emi Sanai, Mio Nagai, Michiko Horiguchi, Chikamasa Yamashita, Jun-Ichiro Oka
The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine-resistant depression-model mice. In order to utilize GLP-2 as a clinical treatment tool for depression, we herein focused on the intranasal delivery that is non-invasive approach, because the i.c.v. administration is invasive and impractical. In the present study, we prepared a GLP-2 derivative containing cell penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS-CPPs-GLP-2) for the intranasal (i...
January 2017: Peptides
https://www.readbyqxmd.com/read/27886774/analysis-of-tricyclic-antidepressants-in-human-plasma-using-online-restricted-access-molecularly-imprinted-solid-phase-extraction-followed-by-direct-mass-spectrometry-identification-quantification
#19
Mariane Gonçalves Santos, Isabela Maria Campos Tavares, Adriano Francisco Barbosa, Jefferson Bettini, Eduardo Costa Figueiredo
The use of a new class of hybrid materials, called restricted access molecularly imprinted polymers (RAMIPs) seems to present a good strategy for the sample preparation of complex matrices, since these materials combine good protein elimination capacity with high degree selectivity. Mass spectrometers (MS) have been successfully used for polar drug identification and quantification. In order to combine the advantages of both RAMIPs and mass spectrometry, we proposed a study that joins these properties in a single system, where we could analyse tricyclic antidepressants from human plasma, without offline extraction or chromatographic separation...
January 15, 2017: Talanta
https://www.readbyqxmd.com/read/27878807/manic-switches-induced-by-antidepressants-an-umbrella-review-comparing-randomized-controlled-trials-and-observational-studies
#20
N Allain, C Leven, B Falissard, J-S Allain, J-M Batail, E Polard, F Montastruc, D Drapier, F Naudet
OBJECTIVE: We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials (RCTs) compared to observational studies (OSs). METHOD: Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode...
February 2017: Acta Psychiatrica Scandinavica
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