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Shi-Xun Ma, Seung-Hwan Kwon, Jee-Yeon Seo, Ji-Young Hwang, Sa-Ik Hong, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Transient receptor potential vanilloid type 1 (TRPV1), the archetypal member of the vanilloid TRP family, was initially identified as the receptor for capsaicin, the pungent ingredient in hot chili peppers. We previously demonstrated that TRPV1 in the dorsal striatum significantly contributes to morphine reward by using the conditioned place preference paradigm in mice; however, it is unknown whether TRPV1 has the same effect in other reward models. In this study, we investigated the role of TRPV1 in morphine reward by using a self-administration paradigm in rats...
October 11, 2016: Addiction Biology
Yao Wang, Ping Huang, Minxi Hu, Wei Huang, Xinyuan Zhu, Deyue Yan
The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effectively. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio...
October 10, 2016: Bioconjugate Chemistry
Mark A Smith, Gaylen E Fronk, Huailin Zhang, Charlotte P Magee, Andrea M Robinson
Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration...
October 5, 2016: Pharmacology, Biochemistry, and Behavior
Anthony L Desbien
A clear index for a response to adjuvants is a change in the cellular composition of lymph nodes draining the site of adjuvant injection (Didierlaurent et al., J Immunol 183:6186-6197, 2009; Caproni et al., J Immunol 188:3088-98, 2012; Desbien et al., Eur J Immunol 1-11, 2014). During the steady state, lymph nodes (LNs) are composed of a fixed ratio of innate and adaptive cells awaiting activation signals from tissue draining lymph. Upon exposure to innate stimulants, lymph nodes undergo dramatic changes. The most apparent change to the lymph node is an increase in size...
2017: Methods in Molecular Biology
Emma Yhnell, Stephen B Dunnett, Simon P Brooks
Huntington's disease (HD) is characterised by motor symptoms which are often preceded by cognitive and behavioural changes, that can significantly contribute to disease burden for people living with HD. Numerous knock-in mouse models of HD are currently available for scientific research. However, before their use, they must be behaviourally characterised to determine their suitability in recapitulating the symptoms of the human condition. Thus, we sought to longitudinally characterise the nature, severity and time course of cognitive and behavioural changes observed in HdhQ111 heterozygous knock-in mice...
2016: PloS One
Scott T Barrett, Trevor N Geary, Amy N Steiner, Rick A Bevins
RATIONALE: Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. OBJECTIVES: The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach...
October 1, 2016: Psychopharmacology
Luyi Zhou, Haley Andersen, Adrian C Arreola, Jill R Turner, Pavel I Ortinski
Withdrawal from cocaine regulates expression of distinct glutamate re-uptake transporters in the nucleus accumbens (NAc). In this study, we examined the cumulative effect of glutamate re-uptake by multiple excitatory amino acid transporters (EAATs) on drug-seeking at two different stages of withdrawal from self-administered cocaine. Rats were trained on fixed ratio 1 (FR1), progressing to FR5 schedule of reinforcement. After one day of withdrawal, microinfusion of a broad non-transportable EAAT antagonist, DL-threo-beta-benzyloxyaspartate (DL-TBOA), into the NAc shell dose-dependently attenuated self-administration of cocaine...
2016: PloS One
Tjard R Schermer, Bas Robberts, Alan J Crockett, Bart P Thoonen, Annelies Lucas, Joke Grootens, Ivo J Smeele, Cindy Thamrin, Helen K Reddel
Clinical guidelines indicate that a chronic obstructive pulmonary disease (COPD) diagnosis is made from a single spirometry test. However, long-term stability of diagnosis based on forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) ratio has not been reported. In primary care subjects at risk for COPD, we investigated shifts in diagnostic category (obstructed/non-obstructed). The data were from symptomatic 40+ years (ex-)smokers referred for diagnostic spirometry, with three spirometry tests, each 12±2 months apart...
September 29, 2016: NPJ Primary Care Respiratory Medicine
Claudia Campos, Yanerys Leon, Andressa Sleiman, Beatriz Urcuyo
One potential limitation of functional communication training (FCT) is that after the functional communication response (FCR) is taught, the response may be emitted at high rates or inappropriate times. Thus, schedule thinning is often necessary. Previous research has demonstrated that multiple schedules can facilitate schedule thinning by establishing discriminative control of the communication response while maintaining low rates of problem behavior. To date, most applied research evaluating the clinical utility of multiple schedules has done so in the context of behavior maintained by positive reinforcement (e...
September 27, 2016: Behavior Modification
Vanita R Aroda, Julio Rosenstock, Carol Wysham, Jeffrey Unger, Diego Bellido, Guillermo González-Gálvez, Akane Takami, Hailing Guo, Elisabeth Niemoeller, Elisabeth Souhami, Richard M Bergenstal
OBJECTIVE: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m(2)) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5...
September 20, 2016: Diabetes Care
Lisa R Gerak, Gregory T Collins, Charles P France
Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C (5-HT2C) receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion)...
September 20, 2016: Journal of Pharmacology and Experimental Therapeutics
Katherine M Serafine, Kenner C Rice, Charles P France
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0...
September 2016: Journal of the Experimental Analysis of Behavior
James Winearls, Michael Reade, Helen Miles, Andrew Bulmer, Don Campbell, Klaus Görlinger, John F Fraser
Hemorrhage in the setting of severe trauma is a leading cause of death worldwide. The pathophysiology of hemorrhage and coagulopathy in severe trauma is complex and remains poorly understood. Most clinicians currently treating trauma patients acknowledge the presence of a coagulopathy unique to trauma patients-trauma-induced coagulopathy (TIC)-independently associated with increased mortality. The complexity and incomplete understanding of TIC has resulted in significant controversy regarding optimum management...
October 2016: Anesthesia and Analgesia
Jin-Young Jang, Taesung Park, Selyeong Lee, Yongkang Kim, Seung Yeoun Lee, Sun-Whe Kim, Song-Cheol Kim, Ki-Byung Song, Masakazu Yamamoto, Takashi Hatori, Seiko Hirono, Sohei Satoi, Tsutomu Fujii, Satoshi Hirano, Yasushi Hashimoto, Yashuhiro Shimizu, Dong Wook Choi, Seong Ho Choi, Jin Seok Heo, Fuyuhiko Motoi, Ippei Matsumoto, Woo Jung Lee, Chang Moo Kang, Ho-Seong Han, Yoo-Seok Yoon, Masayuki Sho, Hiroaki Nagano, Goro Honda, Sang Geol Kim, Hee Chul Yu, Jun Chul Chung, Yuichi Nagakawa, Hyung Il Seo, Hiroki Yamaue
OBJECTIVES: This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. BACKGROUND: Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. METHODS: Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan...
September 6, 2016: Annals of Surgery
Samy Figueiredo, Audrey Tantot, Jacques Duranteau
Viscoelastic haemostatic assays (VHAs), mainly thromboelastography (TEG) and the rotational thromboelastometry (ROTEM), provide global information on clot formation and dissolution at patient bedside, allowing fast identification of coagulation disorders. In trauma patients, VHAs are able to predict massive transfusion and mortality. These devices might also be used for applying targeted administration of procoagulant factors (e.g. fibrinogen concentrate) as an alternative to or in addition to using predefined fixed ratios of red blood cells: platelets: fresh frozen plasma/cryoprecipitate...
September 8, 2016: Minerva Anestesiologica
Tyra P Sellers, Kristen Kelley, Thomas S Higbee, Katie Wolfe
Young children with autism may fail to mand using a range of frames (e.g., "I want," "May I have," "Please give me"). We examined the effects of simultaneous script training and script fading on acquisition and maintenance of varied mand frames with six preschool children with autism. For participants who did not demonstrate increased mand variability under fixed-ratio (FR) 1 conditions, we assessed the effects of post script-training extinction on response variability. Following training of up to four different mand frames, three of six participants emitted more varied mands under FR1 conditions relative to baseline...
June 2016: Analysis of Verbal Behavior
Stefan Karrasch, Irene Brüske, Maia P Smith, Barbara Thorand, Cornelia Huth, Karl-Heinz Ladwig, Florian Kronenberg, Joachim Heinrich, Rolf Holle, Annette Peters, Holger Schulz
BACKGROUND: There is an ongoing debate about the appropriate spirometric criterion for airway obstruction to detect COPD. Furthermore, the association of different criteria with comorbidity prevalence and inflammatory biomarkers in advanced age is unclear. MATERIALS AND METHODS: Spirometry was performed in a population-based study (n=2,256) covering an age range of 41-90 years. COPD was spirometrically determined either by a fixed ratio (FR) of <0.7 for forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) or by FEV1/FVC below the lower limit of normal (LLN)...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Sarah L Anderson, Jennifer M Trujillo
IN BRIEF The combination of basal insulin and a glucagon-like peptide 1 receptor agonist is becoming increasingly common and offers several potential benefits to patients with type 2 diabetes. Clinical studies have demonstrated improved glycemic control and low risks of hypoglycemia and weight gain with the combination, which provides a safe and effective alternative to basal-bolus insulin with less treatment burden. Fixed-ratio combination products that administer both agents in a single injection are in the pipeline and will offer additional options for clinicians and patients...
August 2016: Diabetes Spectrum: a Publication of the American Diabetes Association
M F Lazenka, J A Suyama, C T Bauer, M L Banks, S S Negus
3,4-methylenedioxymethamphetamine (MDMA) is a substrate for the dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats...
August 23, 2016: Pharmacology, Biochemistry, and Behavior
Marsida Kallupi, Giulia Scuppa, Giordano de Guglielmo, Girolamo Calò, Friedbert Weiss, Michael A Statnick, Linda M Rorick-Kehn, Roberto Ciccocioppo
The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0...
August 26, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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