bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of three diaminopyrimidines as potent and selective antagonists of P2X3 and P2X2/3 receptors with in vivo efficacy in a pain model
Authors: Ballini E , Virginio C , Medhurst SJ , Summerfield SG , Aldegheri L , Buson A , Carignani C , Chen YH , Giacometti A , Lago I , Powell AJ , Jarolimek W 
Published: March 2011

BACKGROUND AND PURPOSE P2X3 and P2X2/3 receptors are highly localized on the peripheral and central pathways of nociceptive signal transmission. The discovery of A‐317491 allowed their validation as chronic inflammatory and neuropathic pain targets, but this molecule has a very limited oral bioavailability and CNS penetration. Recently, potent P2X3 and P2X2/3 blockers with a diaminopyrimidine core group and better bioavailability were synthesized and represent a new opportunity for the validation of P2X3‐containing receptors as targets for pain. Here we present a characterization of three representative diaminopyrimidines.EXPERIMENTAL APPROACH The activity of compounds was evaluated in intracellular calcium flux and electrophysiological recordings from P2X receptors expressed in mammalian cells and in a in vivo model of inflammatory pain (complete Freund's adjuvant (CFA) in rat paws).KEY RESULTS Compound A potently blocked P2X3 (pIC50 = 7.39) and P2X2/3 (pIC50 = 6.68) and showed no detectable activity at P2X1, P2X2, P2X4 and P2X7 receptors (pIC50 < 4.7). Whole‐cell voltage clamp electrophysiology confirmed these results. Compounds showed good selectivities when tested against a panel of different classes of target. In the CFA model, compound B showed significant anti‐nociceptive effects (57% reversal at 3 mg·kg−1).CONCLUSIONS AND IMPLICATIONS The diaminopyrimidines were potent and selective P2X3 and P2X2/3 receptor antagonists, showing efficacy in vivo and represent useful tools to validate these receptors as targets for inflammatory and neuropathic pain and provide promising progress in the identification of therapeutic tools for the treatment of pain‐related disorders.
Sex‐dependent control of murine emotional‐affective behaviour in health and colitis by peptide YY and neuropeptide Y
Authors: Painsipp Evelin , Herzog Herbert , Sperk Günther , Holzer Peter 
Published: March 2011

BACKGROUND AND PURPOSE Peptide YY (PYY) and neuropeptide Y (NPY) are involved in regulating gut and brain function. Because gastrointestinal inflammation is known to enhance anxiety, we explored whether experimental colitis interacts with genetic deletion (knockout) of PYY and NPY to alter emotional‐affective behaviour.EXPERIMENTAL APPROACH Male and female wild‐type, NPY (NPY−/−), PYY (PYY−/−) and NPY−/−; PYY−/− double knockout mice were studied in the absence and presence of mild colitis induced by ingestion of dextran sulphate sodium (2%) in drinking water. Anxiety‐like behaviour was tested on the elevated plus maze and open field, and depression‐like behaviour assessed by the forced swim test.KEY RESULTS In the absence of colitis, anxiety‐like behaviour was increased by deletion of NPY but not PYY in a test‐ and sex‐dependent manner, while depression‐like behaviour was enhanced in NPY−/− and PYY−/− mice of either sex. The severity of DSS‐induced colitis, assessed by colonic myeloperoxidase content, was attenuated in NPY−/− but not PYY−/− mice. Colitis modified anxiety‐ and depression‐related behaviour in a sex‐, genotype‐ and test‐related manner, and knockout experiments indicated that NPY and PYY were involved in some of these behavioural effects of colitis.CONCLUSIONS AND IMPLICATIONS These data demonstrate sex‐dependent roles of NPY and PYY in regulation of anxiety‐ and depression‐like behaviour in the absence and presence of colitis. Like NPY, the gut hormone PYY has the potential to attenuate depression‐like behaviour but does not share the ability of NPY to reduce anxiety‐like behaviour.
The Behaviors of Long‐Term Cryopreserved Human Hepatocytes on Different Biomaterials
Authors: Lu Jui‐Nan , Wang Chih‐Chi , Young Tai‐Horng 
Published: March 2011

AbstractIsolated human hepatocytes have been extensively investigated due to clinical demand and scientific interest. With a limited supply of available liver tissue and the rapid loss of liver‐specific functions in vitro, cryopreservation of human hepatocytes serves as an alternative way to maintain availability of hepatocytes. The purpose of this study was to evaluate the biological behaviors of long‐term (more than 4 years) cryopreserved human hepatocytes on biomaterials, including polyvinyl alcohol (PVA), poly(ethylene‐co‐vinyl alcohol), polyvinylidene fluoride, commercial tissue culture polystyrene (TCPS), and collagen‐coated TCPS. Cell attachment was observed by scanning electron microscopy and quantified by lactate dehydrogenase assay. Cell viability was assayed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide reduction activity. Cell functions were determined by albumin secretion and urea synthesis. Results indicated that human hepatocytes could be cryopreserved for more than 4 years without losing liver‐specific functions. Also, PVA was proposed to serve as an appropriate and promising substrate for culturing long‐term cryopreserved hepatocytes, maintaining high cell attachment and high level of liver‐specific functions.
Safe Neuromuscular Electrical Stimulator Designed for the Elderly
Authors: Krenn Matthias , Haller Michael , Bijak Manfred , Unger Ewald , Hofer Christian , Kern Helmut , Mayr Winfried 
Published: March 2011

AbstractA stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge‐balanced biphasic voltage‐controlled stimulation channels. Additionally, the evoked myoelectric signal (M‐wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand‐alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.
Spinal Involvement and Muscle Cramps in Electrically Elicited Muscle Contractions
Authors: Merletti Roberto , Botter Alberto , Lanfranco Fabio , Minetto Marco A. 
Published: March 2011

AbstractElectrical stimulation of innervated muscles has been investigated for many decades with alternations of high and low clinical interest in the fields of rehabilitation medicine and sports sciences. Early work demonstrated that afferent fibers have lower thresholds and are usually activated first (therefore eliciting an H‐reflex). In the case of nerve trunk stimulation, the order of recruitment is mostly conditioned by the axonal dimension and excitability threshold. In the case of muscle motor point stimulation, the spatial distribution of nerve branches plays a predominant role. Sustained stimulation produces a progressive increase of force that is often maintained in subsequent voluntary activation by stroke patients. This observation suggested a facilitation mechanism at the spinal and/or supraspinal level. Such facilitation has been observed in healthy subjects as well, and may explain the generation of cramps elicited during stimulation and sustained for dozens of seconds after the stimulation has been interrupted. The most recent interpretations of facilitation resulting from peripheral stimulation focused on presynaptic (potentiation of neurotransmitter release from afferent fibers) or postsynaptic (generation of “persistent inward currents” in spinal motor neurons or interneurons) mechanisms. The renewed attention to these phenomena is once more increasing the interest toward electrical stimulation of the neuromuscular system. This is an opportunity for a structured investigation of the field aimed to resolving elements of confusion and controversy that still plague this area of electrophysiology.
A Study on Feedback Error Learning Controller for Functional Electrical Stimulation: Generation of Target Trajectories by Minimum Jerk Model
Authors: Watanabe Takashi , Fukushima Keisuke 
Published: March 2011

AbstractThe Feedback Error Learning controller was found to be applicable to functional electrical stimulation control of wrist joint movements in control with subjects and computer simulation tests in our previous studies. However, sinusoidal trajectories were only used for the target joint angles and the artificial neural network (ANN) was trained for each trajectory. In this study, focusing on two‐point reaching movement, target trajectories were generated by the minimum jerk model. In computer simulation tests, ANNs trained with different number of target trajectories under the same total number of control iterations (50 control trials) were compared. The inverse dynamics model (IDM) of the controlled limb realized by the trained ANN decreased the output power of the feedback controller and improved tracking performance to unlearned target trajectories. The IDM performed most effectively when target trajectory was changed every one control trial during ANN training.
Comparison of Verbal Learning and Memory in Children With Heavy Prenatal Alcohol Exposure or Attention‐Deficit/Hyperactivity Disorder
Authors: Crocker Nicole , Vaurio Linnea , Riley Edward P. , Mattson Sarah N. 
Published: March 2011

Background:  Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning and recall. However, the specificity of these deficits has not been adequately tested. In the current study, verbal learning and memory performance of children with heavy prenatal alcohol exposure was compared to children with attention‐deficit/hyperactivity disorder (ADHD), a disorder commonly seen in alcohol‐exposed children.Methods:  Performance on the California Verbal Learning Test—Children’s Version (CVLT‐C) was examined in 3 groups of children (N = 22/group): (i) heavy prenatal alcohol exposure and ADHD (ALC), (ii) nonexposed with ADHD (ADHD), and (iii) nonexposed typically developing (CON). Groups were matched on age, sex, race, ethnicity, handedness, and socioeconomic status (SES).Results:  Group differences were noted on learning trials (CON > ADHD > ALC). On the delayed recall trial, CON children performed better than both clinical groups, who did not differ from each other. Children in the ALC group demonstrated poorer recognition than children in the CON and ADHD groups, who did not differ from each other. Marginally significant group differences were noted on retention of previously learned material. Post hoc analyses indicated that ADHD children showed worse retention relative to the CON group, whereas retention in the ALC children remained intact.Conclusions:  These data suggest that children with heavy prenatal alcohol exposure and nonexposed children with ADHD show differential patterns of deficit on the CVLT‐C. Performance of alcohol‐exposed children reflects inefficient encoding of verbal material, whereas performance of the ADHD group may be better characterized by a deficit in retrieval of learned material. Differences noted between clinical groups add to a growing neurobehavioral profile of FASD that may aid in differential diagnosis.
The Effect of Naltrexone on Alcohol’s Stimulant Properties and Self‐Administration Behavior in Social Drinkers: Influence of Gender and Genotype
Authors: Setiawan Elaine , Pihl Robert O. , Cox Sylvia M. L. , Gianoulakis Christina , Palmour Roberta M. , Benkelfat Chawki , Leyton Marco 
Published: March 2011

Background:  Few pharmacological treatments for alcohol dependence are available. Moreover, the best supported treatment, naltrexone hydrochloride, appears to work for only some.Methods:  To investigate potential predictors of these differential responses, 40 social drinkers (20 women) were administered 6 days of treatment with naltrexone vs. placebo in a double‐blind, counterbalanced, crossover design. At the end of each treatment period, participants received a single dose of their preferred alcoholic beverage followed by the opportunity to work for additional alcohol units using a progressive ratio (PR) breakpoint paradigm. All subjects but one were genotyped for the A118G polymorphism of the mu opioid receptor gene (OPRM1).Results:  Naltrexone decreased the ethanol‐induced ‘euphoria’ to a priming dose of alcohol in two subgroups: (i) in women, and (ii) in subjects with the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone did not decrease motivation to work for additional alcoholic beverages on the PR task regardless of gender or genotype.Conclusions:  The results add to the evidence that naltrexone decreases positive subjective effects of alcohol, with preferential effects in distinct subgroups. Similar effects in heavier drinkers might decrease alcohol use.
Age at First Drink Moderates the Impact of Current Stressful Life Events on Drinking Behavior in Young Adults
Authors: Blomeyer Dorothea , Buchmann Arlette F. , Schmid Brigitte , Jennen‐Steinmetz Christine , Schmidt Martin H. , Banaschewski Tobias , Laucht Manfred 
Published: March 2011

Background:  Recent evidence from animal experiments and studies in humans suggests that early age at first drink (AFD) may lead to higher stress‐induced drinking. The present study aimed to extend these findings by examining whether AFD interacted with stressful life events (SLE) and/or with daily hassles regarding the impact on drinking patterns among young adults.Method:  In 306 participants of an epidemiological cohort study, AFD was assessed together with SLE during the past 3 years, daily hassles in the last month, and drinking behavior at age 22. As outcome variables, 2 variables were derived, reflecting different aspects of alcohol use: the amount of alcohol consumed in the last month and the drinking frequency, indicated by the number of drinking days in the last month.Results:  Linear regression models revealed an interaction effect between the continuous measures of AFD and SLE on the amount of alcohol consumed. The earlier young adults had their first alcoholic drink and the higher the levels of SLE they were exposed to, the disproportionately more alcohol they consumed. Drinking frequency was not affected by an interaction of these variables, while daily hassles and their interaction with AFD were unrelated to drinking behavior.Conclusions:  These findings highlight the importance of early age at drinking onset as a risk factor for later heavy drinking under high load of SLE. Prevention programs should aim to raise age at first contact with alcohol. Additionally, support in stressful life situations and the acquisition of effective coping strategies might prevent heavy drinking in those with earlier drinking onset.
No Longer Undertreated? Depression Diagnosis and Antidepressant Therapy in Elderly Long‐Stay Nursing Home Residents, 1999 to 2007
Authors: Gaboda Dorothy , Lucas Judith , Siegel Michele , Kalay Ece , Crystal Stephen 
Published: March 2011

OBJECTIVES: To examine the evolution of depression identification and use of antidepressants in elderly long‐stay nursing home residents from 1999 through 2007 and the associated sociodemographic and facility characteristics.DESIGN: Annual cross‐sectional analysis of merged resident assessment data from the Minimum Data Set (MDS) and facility characteristics from the Online Survey Certification and Reporting data.SETTING: Nursing homes in eight states (5,445 facilities).PARTICIPANTS: Long‐stay nursing home residents aged 65 and older (2,564,687 assessments).MEASUREMENTS: Physician‐documented depression diagnoses recorded in the MDS were used to identify residents with depression; antidepressant use was measured using MDS information about residents' receipt of an antidepressant in the 7 days before assessment.RESULTS: Diagnosis of depression and antidepressant therapy in residents diagnosed increased at a rapid rate. By 2007, 51.8% of residents were diagnosed with depression, 82.8% of whom received an antidepressant. Adjusted odds of treatment were higher for younger residents, whites, and those with moderate impairment of cognitive function.CONCLUSION: This study demonstrates striking increases in depression diagnosis and treatment with antidepressant medications, but disparities persist without clear evidence about underlying mechanisms. More research is needed to assess effectiveness of antidepressant prescribing.
Patients Treated with Catheter Ablation for Atrial Fibrillation Have Long‐Term Rates of Death, Stroke, and Dementia Similar to Patients Without Atrial Fibrillation
Authors: BUNCH T. JARED , CRANDALL BRIAN G. , WEISS J. PETER , MAY HEIDI T. , BAIR TAMI L. , OSBORN JEFFREY S. , ANDERSON JEFFREY L. , MUHLESTEIN JOSEPH B. , HORNE BENJAMIN D. , LAPPE DONALD L. , DAY JOHN D. 
Published: March 2011

Outcomes in Patients With AF. Introduction: Atrial fibrillation (AF) adversely impacts mortality, stroke, heart failure, and dementia. AF ablation eliminates AF in most patients. We evaluated the long‐term impact of AF ablation on mortality, heart failure (HF), stroke, and dementia in a large system‐wide patient population. Methods: A total of 4,212 consecutive patients who underwent AF ablation were compared (1:4) to 16,848 age/gender matched controls with AF (no ablation) and 16,848 age/gender matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain AF study and were followed for at least 3 years. Results: Of the 37,908 patients, mean age 65.0 ± 13 years, 5,667 (14.9%) died, 1,296 (3.4%) had a stroke, and 1,096 (2.9%) were hospitalized for HF over >3 years of follow‐up. AF ablation patients were less likely to have diabetes, but were more likely to have hypertension, HF, and significant valvular heart disease. AF ablation patients had a lower risk of death and stroke in comparison to AF patients without ablation. Alzheimer's dementia occurred in 0.2% of the AF ablation patients compared to 0.9% of the AF no ablation patients and 0.5% of the no AF patients (P < 0.0001). Other forms of dementia were also reduced significantly in those treated with ablation. Compared to patients with no AF, AF ablation patients had similar long‐term rates of death, dementia, and stroke. Conclusions: AF ablation patients have a significantly lower risk of death, stroke, and dementia in comparison to AF patients without ablation. AF ablation may eliminate the increased risk of death and stroke associated with AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 839‐845, August 2011)
Erratum
Authors: Luoto R , Matomäki J , Isolauri E , Lehtonen L 
Published: March 2011

‘Incidence of necrotizing enterocolitis in very‐low‐birth‐weight infants related to the use of Lactobacillus GG’ published in Acta Paediatrica (2010;99:1135–8)Our recent article, examining retrospectively the incidence of necrotizing enterocolitis (NEC) in all five university hospital NICUs in Finland in relation to the use of LGG, demonstrated that the incidence of NEC was 4.6% vs. 3.3% vs. 1.8% in the prophylactic LGG group, the no probiotics group and the probiotics ‘on demand’ group, respectively; p = 0.0090, Chi‐Square. This is correctly presented in the result section of the manuscript. Unfortunately in the abstract the latter two groups, i.e. the no probiotics group and the probiotics ‘on demand’ group, were reported in wrong order.We wish this type of error, kindly brought to our attention only recently by colleagues from Australia and Denmark, to be corrected. Further, we find this correction of most importance for the readers paying more attention to the abstracts than to the articles.The conclusion of our paper remains, however, unchanged: more randomized clinical trials of the specific probiotic strains on the prevention of NEC in the premature infants is urgently needed.
Morphological spectrum of primary epidermal laminae in the forehoof of Thoroughbred horses
Authors: FARAMARZI B. 
Published: March 2011

SummaryReasons for performing the study: Hoof health is a major concern of horse owners as well as the equine industry. However, many questions remain concerning regional variations of laminar junction and its potential to remodel.Hypothesis: To examine regional variations in the morphology of the laminar junction and thickness of the hoof wall in Thoroughbred horses.Methods: The forefeet of 25 Thoroughbred cadavers were examined. Each hoof was divided into 20 blocks through 4 proximodistal slices (below the coronary band, each 1 cm apart) and 5 circumferential positions (toe, medial and lateral quarters and heels). In each block, 25 central primary epidermal laminae (PEL) were considered. Orientation of each lamina in relation to the hoof wall (LO), degree of bending (IA) and the spaces between the adjacent laminae (LS) were measured. Thickness of the hoof wall and number of branched PEL were also measured. Data were analysed using a split‐block design in ANOVA.Results: There were significant differences between the 2 proximal and 2 distal slices in LO and IA data, but not in LS data. Circumferentially, toe blocks were different from heel and quarters blocks. Lateral and medial heels as well as the quarters were mostly different. The hoof wall was slightly thicker laterally than medially. There were more branched PEL on the lateral side of the left hooves and on the medial side of the right hooves.Conclusions: These data add to the circumstantial evidence supporting the hypothesis of adaptive remodelling in the laminar junction. Results of this study signify the capability of PEL to remodel in response to applied stress to the regions of the hoof.Potential relevance: A deeper understanding of the gross and cellular processes of laminar remodelling may well prove to be complementary to an understanding of their failure in laminitis.