bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arachidonic acid metabolites and enzyme transcripts in asthma are altered by cigarette smoking
Authors: Thomson N. C. , Chaudhuri R. , Spears M. , Messow C. M. , Jelinsky S. , Miele G. , Nocka K. , Takahashi E. , Hilmi O. J. , Shepherd M. C. , Miller D. K. , McSharry C. 
Published: February 2014

AbstractBackgroundArachidonic acid metabolites are implicated in the pathogenesis of asthma although only limited information is available on the impact of current smoking history on these metabolites. The aim of the study was to examine the effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations and relevant enzyme transcripts in asthma.MethodsIn 108 smokers and never smokers with asthma and 45 healthy controls [smokers and never smokers], we measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4, induced sputum fluid LTB4, LTE4, PGD2, and PGE2, plasma secretory phospholipase A2 (sPLA2), and 11β prostaglandin F2α (11βPGF2α), and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA expression levels of arachidonic acid metabolic enzymes.ResultsSmokers with asthma had higher urinary LTE4; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012 concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157) vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4(P = 0.013), and plasma 11βPGF2α(P = 0.032), concentrations, respectively, were increased in smokers with asthma compared with healthy smokers. Asthma‐specific and smoking‐related increases (>1.5‐fold expression) in arachidonate 15‐lipoxygenase and gamma‐glutamyltransferase transcripts were demonstrated.ConclusionsSeveral arachidonic acid metabolites and enzyme transcripts involving both lipoxygenase and cyclooxygenase pathways are increased in smokers with asthma and differ from never smokers with asthma. Possibly targeting specific lipoxygenase and cyclooxygenase pathways that are activated by asthma and cigarette smoking may optimize therapeutic responses.
Association between low blood glucose increase during glucose tolerance tests in pregnancy and impaired fetal growth
Authors: Rogne Tormod , Jacobsen Geir W. 
Published: February 2014

AbstractObjectiveTo evaluate how different levels of increase in maternal blood glucose from a fasting state to 2 h after an oral glucose challenge in late pregnancy are associated with fetal growth, with special emphasis on those with a low increase.DesignProspective cohort study.SubjectsWe followed 855 women, of whom 70% had an increased risk for carrying lighter babies.Study design and methodsUltrasound was used to estimate fetal growth in gestational weeks 25, 33 and 37. In week 37 the women had a 75‐g oral glucose tolerance test, and fasting and 2‐h capillary glucose values were recorded with the difference between these two called delta (∆) glucose. Three groups were constructed from the ∆ glucose distribution: Low below the 10th centile; Medium between the 10th and 90th centiles; and High above the 90th centile. Missing data were imputed. Linear and Poisson regression models were applied.Outcome measuresEstimated fetal weight, percent deviation from expected fetal weight and anthropometric measures at birth.ResultsThe Low group carried the lightest fetuses and the High group the heaviest. The fetal growth in the Low group deviated increasingly more in a negative direction from week 25 to 37 than in the other groups.ConclusionIn a high‐risk population, a positive relation between ∆ glucose and fetal growth was found. The Low group demonstrated impaired growth. More attention should be paid to pregnant women with an insufficient increase in glucose after a glucose challenge. Future studies should challenge our findings in high‐risk and low‐risk populations.
Dietary mannanase‐hydrolyzed copra meal improves growth and increases muscle weights in growing broiler chickens
Authors: Ibuki Masahisa , Yoshimoto Yu , Inui Mariko , Fukui Kensuke , Yonemoto Hiroko , Saneyasu Takaoki , Honda Kazuhisa , Kamisoyama Hiroshi 
Published: February 2014

AbstractThe utilization of copra meal as a feed ingredient is limited because it contains a high level of mannan. However, recent findings indicate that the effect of copra meal on growth performance in broiler chickens can be improved by the supplementation of mannanase in the diet. In the present study, we examined the effect of mannanase‐hydrolyzed copra meal (MCM) on growth performance and muscle protein metabolism in growing broiler chickens (Gallus gallus domesticus). Forty 8‐day‐old male broiler chicks were assigned to two groups (four birds in each pen, five replicates) and fed either a commercial diet (as a control diet) or a diet containing MCM at 0.2% until 22 days of age. Dietary MCM significantly increased the weights of body, breast muscle, and thighs in chickens, whereas the weights of abdominal adipose tissue and liver were not affected. Cumulative feed intake was significantly increased by MCM. Dietary MCM significantly decreased plasma 3‐methylhistidine level. The messenger RNA and protein levels of muscle protein metabolism‐related factors were not altered by MCM. These findings suggest that the growth‐promoting effect of MCM is related to the suppression of muscle proteolysis in growing broiler chickens.
Modelling headache and migraine and its pharmacological manipulation
Authors: Erdener S E , Dalkara T 
Published: February 2014

Similarities between laboratory animals and humans in anatomy and physiology of the cephalic nociceptive pathways have allowed scientists to create successful models that have significantly contributed to our understanding of headache. They have also been instrumental in the development of novel anti‐migraine drugs different from classical pain killers. Nevertheless, modelling the mechanisms underlying primary headache disorders like migraine has been challenging due to limitations in testing the postulated hypotheses in humans. Recent developments in imaging techniques have begun to fill this translational gap. The unambiguous demonstration of cortical spreading depolarization (CSD) during migraine aura in patients has reawakened interest in studyingCSDin animals as a noxious brain event that can activate the trigeminovascular system.CSD‐based models, including transgenics and optogenetics, may more realistically simulate pain generation in migraine, which is thought to originate within the brain. The realization that behavioural correlates of headache and migrainous symptoms like photophobia can be assessed quantitatively in laboratory animals, has created an opportunity to directly study the headache in intact animals without the confounding effects of anaesthetics. Headache and migraine‐like episodes induced by administration of glyceryltrinitrate andCGRPto humans and parallel behavioural and biological changes observed in rodents create interesting possibilities for translational research. Not unexpectedly, species differences and model‐specific observations have also led to controversies as well as disappointments in clinical trials, which, in return, has helped us improve the models and advance our understanding of headache. Here, we review commonly used headache and migraine models with an emphasis on recent developments.Linked ArticlesThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2014.171.issue-20
Ethanol self‐administration and nicotine treatment increase brain levels of CYP2D in African green monkeys
Authors: Miller R T , Miksys S , Hoffmann E , Tyndale R F 
Published: February 2014

Background and PurposeCYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self‐administration and nicotine treatment on CYP2D expression in African green monkeys.Experimental ApproachForty monkeys were randomized into control, ethanol‐only, nicotine‐only and ethanol + nicotine groups. Two groups voluntarily self‐administered 10% ethanol in sucrose solution for 4 h·day−1, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg−1 nicotine in saline bid, whereas two groups were injected with saline on the same schedule.Key ResultsBoth nicotine and ethanol dose‐dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2‐fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups.Conclusions and ImplicationsEthanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment‐specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine.
Ginsenoside Rb3 attenuates oxidative stress and preserves endothelial function in renal arteries from hypertensive rats
Authors: Wang Youhua , Dong Jinghui , Liu Ping , Lau Chi Wai , Gao Zhen , Zhou Duan , Tang Jingyi , Ng Chi Fai , Huang Yu 
Published: February 2014

Background and PurposePanax ginseng is commonly used to treat cardiovascular conditions in Oriental countries. This study investigated the mechanisms underlying the vascular benefits of ginsenoside Rb3 (Rb3) in hypertension.Experimental ApproachRings of renal arteries were prepared from spontaneously hypertensive rats (SHRs) and normotensive Wistar‐Kyoto (WKY) rats and were cultured ex vivo for 8 h. Contractile responses of the rings were assessed with myograph techniques. Expression of NADPH oxidases was assessed by Western blotting and immunohistochemistry. Reactive oxygen species (ROS) were measured using dihydroethidium fluorescence imaging and production of NO was determined using the fluorescent NO indicator DAF‐FM diacetate in human umbilical vein endothelial cells.Key ResultsEx vivo treatment with Rb3 concentration‐dependently augmented endothelium‐dependent relaxations, suppressed endothelium‐dependent contractions and reduced ROS production and expressions of NOX‐2, NOX‐4 and p67phox in arterial rings from SHR. Rb3 treatment also normalized angiotensin II (Ang II)‐stimulated elevation in ROS and expression of NOX‐2 and NOX‐4 in arterial rings from WKY rats. Rb3 inhibited Ang II‐induced reduction of NO production and phosphorylation of endothelial NOS in cultures of human umbilical vein endothelial cells. Rb3 also inhibited oxidative stress in renal arterial rings from hypertensive patients or in Ang II‐treated arterial rings from normotensive subjects.Conclusion and ImplicationsEx vivo Rb3 treatment restored impaired endothelial function in arterial rings from hypertensives by reversing over‐expression of NADPH oxidases and over‐production of ROS, and improved NO bioavailability. Our findings suggest that medicinal plants containing Rb3 could decrease oxidative stress and protect endothelial function in hypertension.
Synthesis of Novel Heterocyclic Ring‐Fused 18β‐Glycyrrhetinic Acid Derivatives with Antitumor and Antimetastatic Activity
Authors: Gao Cheng , Dai Fu‐Jun , Cui Hai‐Wei , Peng Shi‐Hong , He Yuan , Wang Xue , Yi Zheng‐Fang , Qiu Wen‐Wei 
Published: February 2014

Glycyrrhetinic acid (GA) is one of the most important triterpenoic acids shows many pharmacological effects, especially antitumor activity. GA triggers apoptosis in various tumor cell lines. However, the antitumor activity of GA is weak, thus the synthesis of new synthetic analogs with enhanced potency is needed. By introducing various five‐member fused heterocyclic rings at C‐2 and C‐3 positions, 18 novel GA derivatives were obtained. These compounds were evaluated for their inhibitory activity against the growth of eight different tumor cell lines using a SRB assay. The most active compound 37 showed IC50 between 5.19 and 11.72 μm, which was about 11‐fold more potent than the lead compound GA. An apoptotic effect of GA and 37 was determined using flow cytometry and trypan blue exclusion assays. We also demonstrated here for the first time that GA and the synthetic derivatives exhibited inhibitory effect on migration of the tested tumor cells, especially 37 which was about 20‐fold more potent than GA on antimetastatic activity.
Oral treatment with SEW2871, a sphingosine-1-phosphate type 1 receptor agonist, ameliorates experimental colitis in interleukin-10 gene deficient mice
Authors: Dong J , Wang H , Wu G , Zhao J , Zhang L , Zuo L , Zhu W , Gong J , Li Y , Gu L , Li J 
Published: February 2014

Summary
SEW2871, a selective sphingosine-1-phosphate type 1 receptor (S1P1) agonist, has been shown to be effective in protecting kidneys against ischaemia–reperfusion injury by reducing CD4+ T cell infiltration in mice. However, the effects of SEW2871 on colitis remain unclear. The aim of this study was to investigate the effects of SEW2871 on established colitis in interleukin (IL)-10 gene-deficient (IL-10–/–) mice, a murine model of Crohn's disease (CD). SEW2871 was administered by gavage at a dose of 20 mg/kg/day for 2 weeks to IL-10–/– mice. Severity of colitis, serum amyloid A, tissue myeloperoxidase (MPO), T cells in blood and colon lamina propria (LP) and proinflammatory cytokine productions were evaluated. Furthermore, the phospho-signal transducer and activator of transcription (STAT)-3 (p-STAT-3) expression in lymphocytes isolated from colon LP was also assessed. The 2-week administration of SEW2871 ameliorated established colitis in IL-10–/– mice, associated with a reduction of serum amyloid A concentration, a decreased colon MPO concentration, a depletion of the peripheral CD4+ CD45+ T cells and a reduction of the homing of T cells into colon LP. Moreover, typical cytokines of T helper type 1 (Th1) and Th17 cells and p-STAT-3 expression were also suppressed by SEW2871 treatment. SEW2871 treatment ameliorates established experimental colitis in IL-10–/– mice, which may provide a new therapeutic approach for human CD therapy.
A new functional assay for the diagnosis of X-linked inhibitor of apoptosis (XIAP) deficiency
Authors: Ammann S , Elling R , Gyrd-Hansen M , Dückers G , Bredius R , Burns S O , Edgar J D M , Worth A , Brandau H , Warnatz K , zur Stadt U , Hasselblatt P , Schwarz K , Ehl S , Speckmann C 
Published: February 2014

Summary
X-linked inhibitor of apoptosis (XIAP) deficiency, caused by mutations in BIRC4, is an immunodeficiency associated with immune dysregulation and a highly variable clinical presentation. Current diagnostic screening tests such as flow cytometry for XIAP expression or lymphocyte apoptosis assays have significant limitations. Based on recent evidence that XIAP is essential for nucleotide-binding and oligomerization domains (NOD)1/2 signalling, we evaluated the use of a simple flow cytometric assay assessing tumour necrosis factor (TNF) production of monocytes in response to NOD2 stimulation by muramyl dipeptides (L18-MDP) for the functional diagnosis of XIAP deficiency. We investigated 12 patients with XIAP deficiency, six female carriers and relevant disease controls. Irrespective of the diverse clinical phenotype, the extent of residual protein expression or the nature of the mutation, the TNF response was severely reduced in all patients. On average, L18-MDP induced TNF production in 25% of monocytes from healthy donors or female carriers, while fewer than 6% of monocytes responded in affected patients. Notably, the assay clearly discriminated affected patients from disease controls with other immunodeficiencies accompanied by lymphoproliferation, hypogammaglobulinaemia or inflammatory bowel disease. Functional testing of the NOD2 signalling pathway is an easy, fast and reliable assay in the diagnostic evaluation of patients with suspected XIAP deficiency.
Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex
Authors: Child Nicholas D. , Stead Matt , Wirrell Elaine C. , Nickels Katherine C. , Wetjen Nicholas M. , Lee Kendall H. , Klassen Bryan T. 
Published: February 2014

SummaryMedically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long‐term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Genome‐wide association analyses of child genotype effects and parent‐of‐origin effects in specific language impairment
Authors: Nudel R. , Simpson N. H. , Baird G. , O'Hare A. , Conti‐Ramsden G. , Bolton P. F. , Hennessy E. R. ,   The SLI Consortium, Ring S. M. , Davey Smith G. , Francks C. , Paracchini S. , Monaco A. P. , Fisher S. E. , Newbury D. F. 
Published: February 2014

AbstractSpecific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome‐wide association study of SLI which included parent‐of‐origin effects and child genotype effects and used 278 families of language‐impaired children. The child genotype effects analysis did not identify significant associations. We found genome‐wide significant paternal parent‐of‐origin effects on chromosome 14q12 (P = 3.74 × 10−8) and suggestive maternal parent‐of‐origin effects on chromosome 5p13 (P = 1.16 × 10−7). A subsequent targeted association of six single‐nucleotide‐polymorphisms (SNPs) on chromosome 5 in 313 language‐impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent‐of‐origin effects. The paternally‐associated SNP on chromosome 14 yields a non‐synonymous coding change within the NOP9 gene. This gene encodes an RNA‐binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent‐of‐origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders.
Climate and host plant availability impact the future distribution of the bean leaf beetle (Cerotoma trifurcata)
Authors: Berzitis Emily A. , Minigan Jordan N. , Hallett Rebecca H. , Newman Jonathan A. 
Published: February 2014

AbstractThe bean leaf beetle, Cerotoma trifurcata, has become a major pest of soybean throughout its North American range. With a changing climate, there is the potential for this pest to further expand its distribution and become an increasingly severe pest in certain regions. To examine this possibility, we developed bioclimatic envelope models for both the bean leaf beetle, and its most important agronomic host plant, soybean (Glycine max). These two models were combined to examine the potential future pest status of the beetle using climate change projections from multiple general circulation models (GCMs) and climate change scenarios. Despite the broad tolerances of soybean, incorporation of host plant availability substantially decreased the suitable and favourable areas for the bean leaf beetle as compared to an evaluation based solely on the climate envelope of the beetle, demonstrating the importance of incorporating biotic interactions in these predictions. The use of multiple GCM–scenario combinations also revealed differences in predictions depending on the choice of GCM, with scenario choice having less of an impact. While the Norwegian model predicted little northward expansion of the beetle from its current northern range limit of southern Ontario and overall decreases in suitable and favourable areas over time, the Canadian and Russian models predict that much of Ontario and Quebec will become suitable for the beetle in the future, as well as Manitoba under the Russian model. The Russian model also predicts expansion of the suitable and favourable areas for the beetle over time. Two predictions that do not depend on our choice of GCM include a decrease in suitability of the Mississippi Delta region and continued favourability of the southeastern United States.