bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model
Authors: Toledo AC , Sakoda CPP , Perini A , Pinheiro NM , Magalhães RM , Grecco S , Tibério IFLC , Câmara NO , Martins MA , Lago JHG , Prado CM 
Published: November 2012

Background and PurposeAsthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti‐inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.Experimental ApproachMale BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin‐sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg–1 per mice) or dexamethasone (5 mg kg–1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL‐5, IL‐4, Eotaxin, IL‐10, TNF‐α, IFN‐γ and GMC‐SF content in lung homogenate was performed by Bioplex assay, and 8‐isoprostane and NF‐kB activations were visualized in inflammatory cells by immunohistochemistry.Key ResultsWe have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro‐inflammatory cytokines and oxidative stress reduction as well as control of NF‐kB activation.Conclusions and ImplicationsThese results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.
Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with HLA-DRB1 shared epitope alleles and disease activity
Authors: Umeda N , Matsumoto I , Ito I , Kawasaki A , Tanaka Y , Inoue A , Tsuboi H , Suzuki T , Hayashi T , Ito S , Tsuchiya N , Sumida T 
Published: November 2012

Summary
To identify and characterize anti-citrullinated glucose-6-phosphate isomerase (GPI) peptide antibodies in patients with rheumatoid arthritis (RA). Nine GPI arginine-bearing peptides in human GPI protein were selected and cyclic citrullinated GPI peptides (CCG-1–9) were constructed. Samples were obtained from RA (n = 208), systemic lupus erythematosus (SLE) (n = 101), Sjögren's syndrome (SS; n = 101) and healthy controls (n = 174). Antibodies against CCG-1–9 were measured, and anti-citrullinated α-enolase-1 (CEP-1), -cyclic citrullinated peptides (CCP) and -GPI proteins antibodies were also examined. Patients with RA were genotyped for HLA-DRB1. The numbers of shared epitope (SE) alleles were counted and compared with those of the autoantibodies. Rabbit GPI was citrullinated with rabbit peptidylarginine deiminase and immunoblot analysis of RA sera performed. The levels of autoantibodies were compared before and after treatment with TNF antagonists in 58 RA patients. Anti-CCG-2, -4 and -7 antibodies were detected in 25·5, 33·2 and 37·0% patients with RA, respectively, and these antibodies were very specific for RA (specificity, 98·1–99·7%). Altogether, 44·2, 86·1 and 13·9% of RA sera were positive for anti-CEP-1, -CCP and -GPI protein antibodies, respectively. Anti-CCG-2, -4 and -7 antibodies were correlated with anti-CCP and anti-CEP-1 antibodies and with the presence of HLA-DRB1 SE alleles. Citrullinated GPI protein was detected using RA sera. Treatment with tumour necrosis factor antagonists reduced significantly the levels of anti-CCG-2 and -7 but not of anti-CEP-1 antibodies. This is the first report documenting the presence of anti-CCG antibodies in RA. Anti-CCG-2 and -7 antibodies could be considered as markers for the diagnosis of RA and its disease activity.
T cell receptor variable β gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus-infected patients with and without mixed cryoglobulinaemia
Authors: Russi S , Lauletta G , Serviddio G , Sansonno S , Conteduca V , Sansonno L , De Re V , Sansonno D 
Published: November 2012

SummaryTo characterize the repertoire of T lymphocytes in chronically hepatitis C virus (HCV)-infected patients with and without mixed cryoglobulinaemia (MC). T cell receptor (TCR) variable (V) β clonalities in portal tracts isolated from liver biopsy sections with a laser capture microdissection technique in 30 HCV-positive MC patients were studied by size spectratyping. Complementarity-determining region 3 (CDR3) profiles of liver-infiltrating lymphocytes (LIL) were also compared with those circulating in the blood. The representative results of TCR Vβ by CDR3 were also obtained from liver tissues and peripheral blood lymphocytes (PBL) of 21 chronically HCV-infected patients without MC. LIL were highly restricted, with evidence of TCR Vβ clonotypic expansions in 23 of 30 (77%) and in 15 of 21 (71%) MC and non-MC patients, respectively. The blood compartment contained TCR Vβ expanded clones in 19 (63%) MC and 12 (57%) non-MC patients. The occurrence of LIL clonalities was detected irrespective of the degree of liver damage or circulating viral load, whereas it correlated positively with higher levels of intrahepatic HCV RNA. These results support the notion that TCR Vβ repertoire is clonally expanded in HCV-related MC with features comparable to those found in chronically HCV-infected patients without MC.
Early biocompatibility of poly (ethylene glycol) hydrogel barrier materials for guided bone regeneration. An in vitro study using human gingival fibroblasts (HGF‐1)
Authors: Dahlin Christer , Johansson Anna , Hoffman Maria , Molenberg Aart 
Published: November 2012

AbstractObjectivesTo evaluate the early cellular attachment and viability to modified polyethylene glycol (PEG) hydrogels with the influence of arginine‐glycine‐aspartic acid (RGD) in an in vitro model system.Material and methodsHuman gingival fibroblasts (HGF‐1) were cultured on 6 different modalities of PEG hydrogel in hydrophobic polystyrene wells. A total of 7500 cells/well (10000 cells/cm2) were dispersed over the PEG filled wells and incubated in triplicates for 24 h, 7 and 13 days. Cell numbers were calculated by means of a NucleoCounter. Cell viability was determined by measuring lactate dehydrogenase (LDH). For statistical analysis, nonparametric Kruska–Wallis test followed by Dunetts T3 test were used.ResultsAll PEG modifications showed good biocompatibility, as demonstrated by low LDH values per cell at the earlier two time points. After 13 days, all PEG modifications showed significantly lower number of cells compared with the controls, and the MX60 configurations demonstrated significantly higher LDH/cell values compared with the other hydrogels.ConclusionsModifications of the physio‐chemical properties of PEG hydrogels and the addition of RGD and spacers influenced the initial cellular response of cultured HGF‐1 cells. With the exception of MX60 after 13 days, all PEG formulations performed similarly well. Early cellular response should be considered when developing PEG‐based material for clinical purposes.
A multicentre, multinational, randomized, placebo‐controlled, double‐blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15‐0444) in patients with type 2 diabetes
Authors: Yang S. J. , Min K. W. , Gupta S. K. , Park J. Y. , Shivane V. K. , Pitale S. U. , Agarwal P. K. , Sosale A. , Gandhi P. , Dharmalingam M. , Mohan V. , Mahesh U. , Kim D. M. , Kim Y. S. , Kim J. A. , Kim P. K. , Baik S. H. 
Published: November 2012

AimThis study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15‐0444) 50 mg versus placebo in patients with type 2 diabetes.MethodsWe conducted a 24‐week, randomized, double‐blind, placebo‐controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single‐blind placebo run‐in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24.ResultsAt week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: −0.71%, 95% confidence interval: −1.04 to −0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo‐subtracted FPG change from baseline at week 24 was −19.80 mg/dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups.ConclusionsThis study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients.
Left Ventricular Rotation and Twist Assessed by Four‐Dimensional Speckle Tracking Echocardiography in Healthy Subjects and Pathological Remodeling: a Single Center Experience
Authors: Lilli Alessio , Baratto Marco Tullio , Meglio Jacopo Del , Chioccioli Marco , Magnacca Massimo , Talini Enrica , Canale Maria Laura , Poddighe Rosa , Comella Alessandro , Casolo Giancarlo 
Published: November 2012

Background: Left ventricular (LV) twist represents a main aspect of ejection. It is defined as the difference between the apical and basal rotation and can be assessed by speckle tracking echocardiography (STE). Twist may be underestimated when assessed by two‐dimensional‐echocardiography due to the difficulty of identifying the real apex. Aim of this study was to evaluate the LV twist by means of three‐dimensional (3D)‐STE and verify if the inclusion of the apex can modify the assessment of the global twist. Methods: LV volume acquisition with a fully sampled matrix array transducer was performed in 30 healthy subjects and 79 patients with cardiomyopathy secondary to different etiologies. Thirty‐nine patients had a LV ejection fraction (EF) ≥50% (Group A), 16 showed an EF between 40 and 50% (Group B), and 24 patients had an EF ≤40%(Group C). LV rotation was assessed by 3D‐STE at basal, medium, apical, and apical‐cap levels. Twist was computed considering the apex either at the apical level (TwistApi) or at the apical‐cap level (TwistAC). Results: LV rotation resulted to be progressively higher from base to apical‐cap (P < 0.0001) with a significant difference between the apex and the apical‐cap level (6.20 ± 3.90° vs. 10.23 ± 7.52°; P < 0.001). Such a difference was constantly found in all Groups (P < 0.01 for Group A, P < 0.05 for Group B and C). TwistApi was also significantly lower than TwistAC both in the overall population (6.2 ± 3.89° vs. 10.23 ± 7.51°; P < 0.001) and in the different subgroups (Controls: 9.61 ± 3.39° vs. 13.75 ± 6.51°; Group A: 10.49 ± 4.77° vs. 16.37 ± 8.49°; Group B: 6.67 ± 3.44° vs. 9.14 ± 5.55°; Group C: 33 ± 2.62° vs. 5.26 ± 3.74°; P < 0.05 for all the comparisons). Conclusions: Identification and inclusion of apical‐cap is relevant for twist assessment and can be carried out efficiently by 3D‐STE. The inclusion of the true apex in the calculation significantly affects the analysis of twist both in normal individuals and patients with different myocardial diseases.
The Effect of Smoking on Myocardial Performance Index in Middle‐Aged Males after First Acute Myocardial Infarction
Authors: Bacaksiz Ahmet , Kayrak Mehmet , Vatankulu Mehmet Akif , Ayhan Selim S. , Sonmez Osman , Akilli Hakan , Aribas Alpay , Ari Hatem , Ozdemir Kurtulus 
Published: November 2012

Background: Cigarette smoking is associated with increased rates of coronary artery disease and acute myocardial infarction (MI). Paradoxically, smokers had lower mortality after MI. The purpose of this study was to evaluate the effect of chronic smoking on myocardial performance index (MPI) in middle‐aged men after an acute MI. Material and methods: A total of 429 patients (325 smokers vs. 104 nonsmokers) presenting with acute ST elevation MI were enrolled in this study. Thrombolysis in myocardial infarction (TIMI) flow of the infarct related artery was measured before and after the primary percutaneous coronary intervention (PCI), and Gensini score was also calculated. Conventional echocardiography and tissue Doppler echocardiography (TDI) were performed within 48–72 hours after onset of chest pain. Peak early (Em) and late (Am) diastolic velocities, peak systolic (Sm) mitral annular velocities and time intervals were recorded with TDI. The MPI, ratio of Em/Am, and E/Em were calculated. Results: Baseline demographic and angiographic characteristics such as Gensini score, pre and, post PCI TIMI flow were similar in 2 groups. In contrast, LV MPI was preserved among smokers (0.59 ± 0.15 vs. 0.66 ± 0.14, P = 0.01), and Em/Am values were also higher in smokers (0.84 ± 0.28 vs. 0.75 ± 0.31, P = 0.01). Independent predictors of impaired MPI (≥0.60) were determined as nonsmoking status (odds ratio 2.940, 95% CI 0.98–5.83, P = 0.05), left anterior descending artery stenosis (odds ratio 3.196, 95% CI 1.73–5.91 P = 0.001), and, age (odds ratio 1.12, 95% CI 1.03–1.22, P = 0.01). Conclusions: Despite similar demographic and angiographic characteristics, smoker males had a paradoxically better MPI after acute MI.
Left Main Coronary In‐Stent Intimal Hyperplasia and Hemodynamics as Detected by Contrast‐Enhanced Transesophageal Echocardiography
Authors: Baglini Roberto , Amaducci Andrea , D'Ancona Giuseppe 
Published: November 2012

Patients and methods: In‐stent hemodynamics were studied by transesophageal echocardiography (TEE) in a group of 54 patients after left main coronary artery stenting, during a 6‐month follow‐up. TEE was performed within 24 hours after stenting and at 1‐ and 3‐month follow‐up. Pulsed wave and color Doppler signals were enhanced by IV administration of Levovist. Results: Angiographic immediate success was obtained in all patients. No in‐hospital death occurred. Ten patients (18.4%) complained of recurrent angina at the follow‐up of 4.8 ± 1.2 months. Both TEE and coronary angiography confirmed in‐stent restenosis in all. Thirty‐nine patients (68.5%) remained symptoms free. Mean late loss in these patients was 0.69 ± 0.20 mm. A linear significant positive relation between mean late loss values and diastolic coronary velocity (r: 0.89, P < 0.001) was found. After 3‐ and 6‐month follow‐up, PDV showed a significant increase in comparison with basal values (0.7 ± 0.3 and 0.6 ± 0.26 vs. 0.32 ± 0.2 cm/sec, P < 0.01). All patients with restenosis showed a significant increase of diastolic coronary velocity in comparison with basal values (2.89 ± 0.25 cm/sec, P < 0.001). Conclusion: TEE can predict the development of in‐stent intimal hyperplasia in patients with unprotected left main coronary artery stenting.
Informal musical activities are linked to auditory discrimination and attention in 2–3‐year‐old children: an event‐related potential study
Authors: Putkinen V. , Tervaniemi M. , Huotilainen M. 
Published: November 2012

AbstractThe relation between informal musical activities at home and electrophysiological indices of neural auditory change detection was investigated in 2–3‐year‐old children. Auditory event‐related potentials were recorded in a multi‐feature paradigm that included frequency, duration, intensity, direction, gap deviants and attention‐catching novel sounds. Correlations were calculated between these responses and the amount of musical activity at home (i.e. musical play by the child and parental singing) reported by the parents. A higher overall amount of informal musical activity was associated with larger P3as elicited by the gap and duration deviants, and smaller late discriminative negativity responses elicited by all deviant types. Furthermore, more musical activities were linked to smaller P3as elicited by the novel sounds, whereas more paternal singing was associated with smaller reorienting negativity responses to these sounds. These results imply heightened sensitivity to temporal acoustic changes, more mature auditory change detection, and less distractibility in children with more informal musical activities in their home environment. Our results highlight the significance of informal musical experiences in enhancing the development of highly important auditory abilities in early childhood.
Daily exposure to cold phase‐shifts the circadian clock of neonatal rats in vivo
Authors: Yoshikawa Tomoko , Matsuno Ami , Yamanaka Yujiro , Nishide Shin‐ya , Honma Sato , Honma Ken‐ichi 
Published: November 2012

AbstractMaternal rhythms entrain the prenatal and neonatal circadian clock in the suprachiasmatic nucleus (SCN) before light entrainment is established. However, the responsible time cues for maternal entrainment are not identified. To examine the role of cyclic changes of ambient temperature in maternal entrainment, blind neonatal rats carrying a clock gene (Per2) bioluminescence reporter were exposed to either of three ambient temperatures (10, 20 or 30 °C) during 6‐h maternal separation in the early light phase. Cold exposure was performed from postnatal day 1 (P1) to P5. On P6, the SCN was harvested and cultured for photometric monitoring of the circadian rhythm in Per2 expression. Here we demonstrate that the daily cold exposure phase‐delayed the circadian Per2 expression rhythms at P6 in a temperature‐dependent manner. Exposure to 10 °C produced the largest phase‐shift of 12.7 h, and exposure to 20 and 30 °C yielded moderate shifts of 4.1 and 4.5 h, respectively. There was no significant difference in the phase‐shifts between the latter two temperatures, indicating that ambient temperature is not the sole factor for the phase‐shift. Behavioral rhythms that developed after weaning reflected the phase‐shift of clock gene expression rhythm in the SCN. These findings indicate that a daily exposure to an ambient temperature of 10 °C during the neonatal period is capable of resetting the circadian clock in the SCN, but other factors yet unidentified are also involved in maternal entrainment.
Regulation of synaptic currents by mGluR2 at reciprocal synapses in the mouse accessory olfactory bulb
Authors: Taniguchi Mutsuo , Yokoi Mineto , Shinohara Yoshiaki , Okutani Fumino , Murata Yoshihiro , Nakanishi Shigetada , Kaba Hideto 
Published: November 2012

AbstractThe throughput of information from the accessory olfactory bulb (AOB) to downstream structures is controlled by reciprocal dendrodendritic inhibition of mitral cells by granule cells. Given the high expression levels of mGluR2, a metabotropic glutamate receptor, in the AOB and the fact that the activation of mGluR2 permits the formation of a specific olfactory memory, we reasoned that mGluR2 might play an important role in regulating dendrodendritic inhibition. To test this hypothesis, we examined the effects of pharmacological and genetic manipulations of mGluR2 on synaptic responses measured from mitral or granule cells in slice preparations from 23‐ to 36‐day‐old Balb/c mice. To evoke dendrodendritic inhibition, a depolarizing voltage step from –70 to 0 mV or a threshold current stimulus adjusted to elicit action potential(s) was applied to a mitral cell using either a nystatin‐perforated or conventional whole‐cell configuration. We found that an agonist for group II metabotropic glutamate receptors (mGluR2/mGluR3), DCG‐IV [(2S,1′R,2′R,3′R)‐2‐(2,3‐dicarboxycyclopropyl)glycine], suppressed, whereas the mGluR2/mGluR3 antagonist LY341495 [(αS)‐α‐amino‐α‐[(1S,2S)‐2‐carboxycyclopropyl]‐9H‐xanthine‐9‐propanoic acid] enhanced dendrodendritic inhibition. Genetic ablation of mGluR2 markedly impaired the effects of DCG‐IV and LY341495 on dendrodendritic inhibition. DCG‐IV reduced both the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents recorded from granule cells. Additionally, DCG‐IV inhibited high‐voltage‐activated calcium currents in both mitral and granule cells. These results suggest that mGluR2 reduces dendrodendritic inhibition by inhibiting synaptic transmission between mitral cells and granule cells in the AOB.
Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero
Authors: Campbell Ellen , Devenney Emma , Morrow Jim , Russell Aline , Smithson William Henry , Parsons Linda , Robertson Iain , Irwin Beth , Morrison Patrick J. , Hunt Stephen , Craig John 
Published: November 2012

SummaryPurpose:  Use of antiepileptic drugs in pregnancy is associated with congenital malformations and developmental delay. Previous studies have suggested that women who have had one child with a congenital malformation are at increased risk of having other children with malformations. We sought to confirm the magnitude of risk in a large cohort drawn from the United Kingdom Epilepsy and Pregnancy Register.Methods:  The United Kingdom Epilepsy and Pregnancy Register is a prospective, observational registration and follow‐up study set up to determine the relative safety of antiepileptic drugs in pregnancy. We have extracted data for those women who prospectively registered more than one pregnancy and calculated the recurrence risks for fetal malformations.Key Findings:  Outcome data were available for 1,534 pregnancies born to 719 mothers. For women whose first child had a congenital malformation there was a 16.8% risk of having another child with a congenital malformation, compared with 9.8% for women whose first child did not have a malformation (relative risk 1.73, 95% confidence interval [CI] 1.01–2.96). The risk for recurrence was 50% for women who had had two previous children with a congenital malformation. There was a trend toward a higher risk for recurrent malformations in pregnancies exposed to valproate (21.9%, relative risk 1.47, 95% CI 0.68–3.20) and topiramate (50%, relative risk 4.50, 95% CI 0.97–20.82), but not for other drugs such as carbamazepine and lamotrigine. Recurrence risks were also higher for pregnancies exposed to polytherapy regimens and for those where the dose of antiepileptic drug treatment had been increased after the first pregnancy.Significance:  Women who have had a child with a malformation are at increased risk of having other children with malformations. This is in keeping with previous reports that have suggested that genetic influences may be one of the factors determining the teratogenic risk of antiepileptic drugs.