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https://www.readbyqxmd.com/read/27923259/-established-therapies-and-new-therapeutic-strategies-in-alcoholic-liver-disease
#1
Helmut Karl Seitz, Sebastian Mueller
Chronical alcohol abuse causes more than 200 diseases and/or symptoms and among these alcoholic liver disease (ALD) is of special importance since it occurs frequently and may be life-threatening. In Europe alcohol consumption as well as ALD increased as compared to the rest of the world. It has been estimated that in Europe approximately 500 000 people die every year due to ALD. ALD consists of alcoholic fatty liver, alcoholic steatohepatitis (ASH), alcoholic cirrhosis and hepatocellar cancer (HCC ). Alcohol hepatitis (AH) is a clinical feature with jaundice and liver failure and a high mortality...
December 6, 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27923051/electrophysiological-characteristics-of-human-ipsc-derived-cardiomyocytes-for-the-assessment-of-drug-induced-proarrhythmic-potential
#2
Wataru Yamamoto, Keiichi Asakura, Hiroyuki Ando, Tomohiko Taniguchi, Atsuko Ojima, Takaaki Uda, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Norimasa Miyamoto, Hiroyuki Tashibu, Takashi Yoshinaga, Daiju Yamazaki, Atsushi Sugiyama, Yasunari Kanda, Kohei Sawada, Yuko Sekino
The aims of this study were to (1) characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond to clinical properties such as QT-RR relationship, (2) determine the applicability of QT correction and analysis methods, and (3) determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP). Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA) platform with and without ion channel antagonists in the recording solution...
2016: PloS One
https://www.readbyqxmd.com/read/27922639/mesolimbic-leptin-signaling-negatively-regulates-cocaine-conditioned-reward
#3
M Shen, C Jiang, P Liu, F Wang, L Ma
The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922595/memories-of-opiate-withdrawal-emotional-states-correlate-with-specific-gamma-oscillations-in-the-nucleus-accumbens
#4
Cyril Dejean, Mathieu Sitko, Paul Girardeau, Amine Bennabi, Stéphanie Caillé, Martine Cador, Thomas Boraud, Catherine Le Moine
Affective memories associated with the negative emotional state experienced during opiate withdrawal are central in maintaining drug-taking, seeking and relapse. Nucleus accumbens (NAC) is a key structure both for acute withdrawal and withdrawal memories reactivation, however NAC neuron coding properties underpinning the expression of these memories remain largely unknown. Here we aimed at deciphering the role of NAC neurons in the encoding and retrieval of opiate withdrawal memory. Chronic single neuron and local field potentials recordings were performed in morphine-dependent rats and placebo-controls...
December 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27922548/methylcobalamin-prevents-mutant-superoxide-dismutase-1-induced-motor-neuron-death-in-vitro
#5
Shunsuke Ito, Yukina Izumi, Tetsuhiro Niidome, Yuichi Ono
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model...
December 2, 2016: Neuroreport
https://www.readbyqxmd.com/read/27922542/generalization-of-serotonin-and-dopamine-ligands-to-the-discriminative-stimulus-effects-of-different-doses-of-%C3%A2-3-4-methylenedioxymethamphetamine
#6
Jeremy I Webster, David N Harper, Susan Schenk
Studies that have attributed the discriminative stimulus effects of ±3,4-methylenedioxymethamphetamine (MDMA) to serotonergic mechanisms typically use a relatively low training dose of 1.5 mg/kg. The role of serotonin in the discriminative stimulus effects of higher doses of MDMA is, however, unknown. Separate groups of rats were trained to discriminate MDMA (1.5 or 3.0 mg/kg) from saline using a two-lever, food-reinforced drug-discrimination procedure. Generalization tests were carried out with a range of serotonin and dopamine ligands...
December 2, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27922541/effects-of-the-5-ht1a-receptor-agonists-buspirone-and-8-oh-dpat-on-pupil-size-in-common-marmosets
#7
Manato Kotani, Naoko Urushino, Itaru Natsutani, Yuji Ogi, Kazuhito Ikeda
As pupil size is affected by psychotropic drugs in all mammals, it has been used as a well-established clinical indicator for the preclinical and clinical development of novel drugs. It has been reported that activation of the serotonin (5-HT)1A receptor differently affects pupil response in rodents (mydriasis) and humans (miosis). Thus, it is important to establish a quantitative system for measuring pupil size using other species, such as nonhuman primates. Common marmosets have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field because of handling ease compared with other nonhuman primates and the requirement for small amounts of test drugs...
December 2, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#8
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#9
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27921140/cocaine-administration-dose-dependently-increases-sexual-desire-and-decreases-condom-use-likelihood-the-role-of-delay-and-probability-discounting-in-connecting-cocaine-with-hiv
#10
Matthew W Johnson, Evan S Herrmann, Mary M Sweeney, Robert S LeComte, Patrick S Johnson
OBJECTIVES: Although cocaine use has been linked to sexual HIV risk behavior for decades, the direct effects of cocaine on sexual desire and sexual decision-making are unexamined. Research suggests delay discounting (devaluation of future outcomes) and probability discounting (devaluation of uncertain outcomes) play roles in condom use decisions. This study examined the effect of cocaine administration on sexual desire, hypothetical condom use, and discounting tasks. METHODS: This double-blind, within-subjects study compared the effects of 0, 125, and 250 mg/70 kg oral cocaine HCl in 12 cocaine users...
December 5, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27921039/clinical-manifestation-and-management-of-adpkd-in-western-countries
#11
REVIEW
Claudia Sommerer, Martin Zeier
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease in Western countries. The prevalence is between 2.4/10,000 and 3.9/10,000. ADPKD represents a systemic disease resulting in deterioration in renal function. Until now, mutations in two genes (PKD1 and PKD2) have been identified. Recently, the European Medicines Agency (EMA) approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency connected with ADPKD in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27921038/the-clinical-manifestation-and-management-of-autosomal-dominant-polycystic-kidney-disease-in-china
#12
REVIEW
Cheng Xue, Chen-Chen Zhou, Ming Wu, Chang-Lin Mei
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27920802/the-role-of-drugs-in-bone-pain
#13
REVIEW
Francesco Marras, Paolo Tranquilli Leali
: Painful symptomatology in the skeletal system can be found in various pathological conditions and can be either localised or diffused. Bone tenderness is common in those who are of an elderly age. TREATMENT STRATEGY: Patients should be informed of the possible causes of their pain and the different therapies that could alleviate it; furthermore they should be encouraged to have an active role in their therapy. It is necessary to prevent the onset of the pain (by the clock) by considering the biological half-life, the bioavailability and the duration of action of the therapy...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27920723/sex-dependent-anti-stress-effect-of-an-%C3%AE-5-subunit-containing-gabaa-receptor-positive-allosteric-modulator
#14
Sean C Piantadosi, Beverly J French, Michael M Poe, Tamara Timić, Bojan D Marković, Mohan Pabba, Marianne L Seney, Hyunjung Oh, Beverley A Orser, Miroslav M Savić, James M Cook, Etienne Sibille
Rationale: Current first-line treatments for stress-related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "α5-PAM"), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27920558/monitoring-the-effects-of-doxorubicin-on-3d-spheroid-tumor-cells-in-real-time
#15
NamHuk Baek, Ok Won Seo, MinSung Kim, John Hulme, Seong Soo A An
Recently, increasing numbers of cell culture experiments with 3D spheroids presented better correlating results in vivo than traditional 2D cell culture systems. 3D spheroids could offer a simple and highly reproducible model that would exhibit many characteristics of natural tissue, such as the production of extracellular matrix. In this paper numerous cell lines were screened and selected depending on their ability to form and maintain a spherical shape. The effects of increasing concentrations of doxorubicin (DXR) on the integrity and viability of the selected spheroids were then measured at regular intervals and in real-time...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27920504/gender-and-age-related-treatment-compliance-in-patients-with-osteoporosis-in-germany
#16
Peyman Hadji, Louis Jacob, Karel Kostev
AIM: The purpose of this study was to analyze treatment compliance in osteoporotic patients treated with osteoporosis medications in Germany. METHODS: Patients included in the analysis had been diagnosed with osteoporosis with or without fractures and started anti-osteoporotic therapy (bisphosphonates, denosumab, or strontium ranelate) between 2011 and 2014 in a general (GP) or orthopedic practice (OP) setting in Germany. Data pertaining to 6,221 individuals followed in GP and 4,044 individuals followed in OP were analyzed retrospectively...
2016: Patient Preference and Adherence
https://www.readbyqxmd.com/read/27920432/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#17
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920312/dental-care-and-medicare-beneficiaries-access-gaps-cost-burdens-and-policy-options
#18
Amber Willink, Cathy Schoen, Karen Davis
Despite the wealth of evidence that oral health is related to physical health, Medicare explicitly excludes dental care from coverage, leaving beneficiaries at risk for tooth decay and periodontal disease and exposed to high out-of-pocket spending. To profile these risks, we examined access to dental care across income groups and types of insurance coverage in 2012. High-income beneficiaries were almost three times as likely to have received dental care in the previous twelve months, compared to low-income beneficiaries-74 percent of whom received no dental care...
December 1, 2016: Health Affairs
https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#19
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919957/simultaneous-administration-of-statins-and-pioglitazone-limits-tumor-growth-in-a-rat-model-of-malignant-glioma
#20
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
December 2016: Anticancer Research
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