bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silymarin Inhibits Cell Cycle Progression and mTOR Activity in Activated Human T Cells: Therapeutic Implications for Autoimmune Diseases
Authors: Gharagozloo Marjan , Javid Elahe N. , Rezaei Abbas , Mousavizadeh Kazem 
Published: March 2013

AbstractSilymarin, a complex flavonolignan from the ‘milk thistle’ (Silybum marianum) plant, exhibits anticarcinogenic, anti‐inflammatory and cytoprotective effects. Several reports have demonstrated immunosuppressive activity of silymarin; however, the molecular mechanisms involved in immunomodulatory activities of silymarin are not fully understood yet. In this study, the effect of silymarin on cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and activated with anti‐CD3 (5 μg/ml) and anti‐CD28 (2 μg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with 10, 50 and 100 μM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24–96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was determined in activated T cells after 72‐hr incubation with silymarin or DMSO. A significant G1 arrest in cell cycle of activated T lymphocytes was found after 96‐hr incubation with 100 μM silymarin without causing cell death. Silymarin also significantly inhibited the level of phospho‐S6 ribosomal protein and mTOR activity in cell lysates of activated T cells after 72‐hr incubation in comparison with DMSO. This study shows that silymarin inhibits cell proliferation through G1 cell cycle arrest and also through the suppression of the mTOR signalling pathway in human activated T lymphocytes in vitro. Characterizing molecular mechanism of such immunomodulatory effects may have a great potential in future practical application of silymarin in transplantation and auoimmunity.
Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers
Authors: Wang Liqing , Hu Zheyi , Deng Xun , Wang Yong , Zhang Zhongyi , Cheng Ze‐Neng 
Published: March 2013

AbstractThis study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G‐3860A), G‐3113A, CYP1A2*1F (C‐163A) and CYP1A2*1B (C‐5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200‐mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7‐dimethylxanthine/caffeine ratios (17X/137X) after administration of 100‐mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high‐performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the ‐3113 AA genotype compared with those with the ‐3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the ‐3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with ‐3860G/‐3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.
Intimate Partner Violence and the Association with Very Preterm Birth
Authors: Watson Lyndsey F. , Taft Angela J. 
Published: March 2013

AbstractBackgroundIntimate partner violence is a major public health problem. It occurs commonly in pregnancy, resulting in adverse events for women and their fetus or children. The objective of this study was to examine the association between intimate partner violence and very preterm birth.MethodsThis population‐based, case‐control study was conducted in Victoria, Australia, from 2002 to 2004. Interviews were conducted with 603 women who had a singleton very preterm birth (20–31 weeks' gestation), 770 women who had a singleton term birth (37 or more completed weeks' gestation), 139 women who had a very preterm twin birth, and 214 women who had a term twin birth. Intimate partner violence was measured using the Composite Abuse Scale, and questions were also asked about fear of partners and violence from others.ResultsPrevalence of intimate partner violence in the past 12 months was 14.9 percent in singleton case women, 11.7 percent in singleton control women, 9.5 percent in twin case women, and 14.7 percent in twin control women. Fear of a previous partner and reporting similar violence experience with someone else were more likely in singleton births (AOR = 1.36; 95% CI 1.03, 1.79) and (AOR = 1.44; 95% CI 1.12, 1.86), respectively. No differences between twin case women and twin control women were observed. When the precipitating cause of very preterm birth was investigated, antepartum hemorrhage was significantly associated with intimate partner violence and all its subscales.ConclusionsThe heterogeneity of causes of very preterm birth may explain the lack of association found with intimate partner violence in pregnancy. Pregnant women have a significant risk of intimate partner violence, which should be a serious concern for all care providers. (BIRTH 40:1 March 2013)
Perceptions of Barriers to Paternal Presence and Contribution During Childbirth: An Exploratory Study from Syria
Authors: Abushaikha Lubna , Massah Rana 
Published: March 2013

AbstractBackgroundThe barriers that face fathers during childbirth are an understudied phenomenon. The objective of our study was to explore Syrian parents' perceptions of barriers to paternal presence and contribution during childbirth.MethodsA descriptive phenomenological qualitative approach based on Colaizzi's method was used with a purposive sample of 23 mothers and 14 fathers recruited from a major public maternity hospital in Syria.ResultsIn our study, four themes on barriers to paternal presence and contribution during childbirth were found: 1) sociocultural influences and rigidity; 2) being unprepared; 3) unsupportive policies and attitudes; and 4) unfavorable reactions and circumstances.ConclusionsCommon and current sociocultural norms in Syria do not encourage fathers to be present or contribute during childbirth. Therefore, establishing culturally sensitive supportive policies and practices is a vital step toward overcoming these barriers. (BIRTH 40:1 March 2013)
Does the CenteringPregnancy Group Prenatal Care Program Reduce Preterm Birth? The Conclusions Are Premature
Authors: Devitt Neal F. 
Published: March 2013

AbstractPrenatal care is promoted as a means to a healthy pregnancy outcome. In the United States great resources have been spent to expand the availability of a program of prenatal care, but without evidence for its effectiveness in the general population. Despite greater access to prenatal care over the last several decades, there has been no improvement in obstetric outcomes, such as preterm delivery. The CenteringPregnancy program of group prenatal visits is a novel form of prenatal care that, according to several studies, has been said to improve satisfaction with prenatal visits and with pregnancy outcomes. A careful reading of the studies shows that those goals are yet to be achieved. Innovation is welcome and essential, but larger studies are needed to achieve statistical significance to demonstrate improved outcome. (BIRTH 40:1 March 2013)
Accuracy of post‐radiotherapy biopsy before salvage radical prostatectomy
Authors: Meeks Joshua J. , Walker Marc , Bernstein Melanie , Kent Matthew , Eastham James A. 
Published: March 2013

Objective
To determine whether post‐radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer.
Patients and Methods
SRP was performed between 1998 and 2011 on 198 patients.
All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external‐beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%).
Results
Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8.
Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%.
Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade.
The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid‐gland.
Conclusions
Radiation‐recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours.
More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP.
Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin
Authors: Weston A H , Egner I , Dong Y , Porter E L , Heagerty A M , Edwards G 
Published: March 2013

Background and PurposePerivascular adipose tissue (PVAT) releases adipocyte‐derived hyperpolarizing factors (ADHFs) that may partly act by opening myocyte K+ channels. The present study in rat and mouse mesenteric arteries aimed to identify the myocyte K+ channel activated by PVAT and to determine whether adiponectin contributed to the hyperpolarizing effects of PVAT.Experimental ApproachMyocyte membrane potential was recorded from de‐endothelialized, non‐contracted rat and mouse mesenteric arteries in the presence and absence of PVAT.Key ResultsThe β3‐adrenoceptor agonist, CL‐316,243 (10 μM), generated PVAT‐dependent, iberiotoxin‐sensitive myocyte hyperpolarizations resulting from BKCa channel opening and which were partially blocked by L‐NMMA (100 μM). Adiponectin (5 μg·mL−1) also produced iberiotoxin‐sensitive hyperpolarizations in PVAT‐denuded arterioles. Activation of myocyte AMP‐activated protein kinase (AMPK) using 5 μM A‐769662 also induced BKCa‐mediated hyperpolarizations. Dorsomorphin abolished hyperpolarizations to CL‐316,243, adiponectin and A‐769662. In vessels from Adipo−/− mice, hyperpolarizations to CL‐316,243 were absent whereas those to A‐769662 and adiponectin were normal. In rat vessels, adipocyte‐dependent hyperpolarizations were blocked by glibenclamide and clotrimazole but those to NS1619 (33 μM) were unaltered.Conclusions and ImplicationsUnder basal, non‐contracted conditions, β3‐adrenoceptor stimulation of PVAT releases an ADHF, which is probably adiponectin. This activates AMPK to open myocyte BKCa channels indirectly and additionally liberates NO, which also contributes to the observed PVAT‐dependent myocyte hyperpolarizations. Clotrimazole and glibenclamide each reversed hyperpolarizations to adiponectin and A‐769662, suggesting the involvement of myocyte TRPM4 channels in the ADHF‐induced myocyte electrical changes mediated via the opening of BKCa channels.
Histamine is required for H3 receptor‐mediated alcohol reward inhibition, but not for alcohol consumption or stimulation
Authors: Vanhanen J , Nuutinen S , Lintunen M , Mäki T , Rämö J , Karlstedt K , Panula P 
Published: March 2013

Background and PurposeConflicting data have been published on whether histamine is inhibitory to the rewarding effects of abused drugs. The purpose of this study was to clarify the role of neuronal histamine and, in particular, H3 receptors in alcohol dependence‐related behaviours, which represent the addictive effects of alcohol.Experimental ApproachAlcohol‐induced conditioned place preference (alcohol‐CPP) was used to measure alcohol reward. Alcohol‐induced locomotor stimulation, alcohol consumption and kinetics were also assessed. mRNA levels were quantified using radioactive in situ hybridization.Key ResultsLow doses of H3 receptor antagonists, JNJ‐10181457 and JNJ‐39220675, inhibited alcohol reward in wild‐type (WT) mice. However, these H3 receptor antagonists did not inhibit alcohol reward in histidine decarboxylase knock‐out (HDC KO) mice and a lack of histamine did not alter alcohol consumption. Thus H3 receptor antagonists inhibited alcohol reward in a histamine‐dependent manner. Furthermore, WT and HDC KO mice were similarly stimulated by alcohol. The expression levels of dopamine D1 and D2 receptors, STEP61 and DARPP‐32 mRNA in striatal subregions were unaltered in HDC KO mice. No differences were seen in alcohol kinetics in HDC KO compared to WT control animals. In addition, JNJ‐39220675 had no effect on alcohol kinetics in WT mice.Conclusions and ImplicationsThese data suggest that histamine is required for the H3 receptor‐mediated inhibition of alcohol‐CPP and support the hypothesis that the brain histaminergic system has an inhibitory role in alcohol reward. Increasing neuronal histamine release via H3 receptor blockade could therefore be a novel way of treating alcohol dependence.Linked ArticlesThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Expression of histamine receptor genes Hrh3 and Hrh4 in rat brain endothelial cells
Authors: Karlstedt K , Jin C , Panula P 
Published: March 2013

Background and PurposeBrain vascular endothelial cells express histamine H1 and H2 receptors, which regulate brain capillary permeability. We investigated whether H3 and H4 receptors are also expressed in these cells and may thus play a role in permeability regulation.Experimental ApproachAn immortalized rat brain endothelial cell line RBE4 was used to assess the presence of H3 and H4 receptors. Reverse transcription‐PCR (RT‐PCR) and sequencing were used to identify the receptor mRNAs. The receptors were stimulated with histamine and immepip, and specific inverse agonists/antagonists ciproxifan and JNJ 7777120 were used to block H3 and H4 receptors, respectively.Key ResultsRT‐PCR of mRNA extracted from cultured immortalized RBE4 cells revealed two rat H4 receptor gene (Hrh4) transcripts, one full‐length (coding sequence 1173 bp), and one with a 164 bp deletion. Also, two rat H3 receptor gene (Hrh3) isoform mRNAs were expressed in RBE4 cells, and sequencing showed they were the full‐length H3 receptor and the 144 bp deletion form. Both histamine and immepip (H3 and H4 receptor agonists) activated the Erk1/2 MAPK pathway in the RBE4 cells and in vivo in brain blood vessels by activating H4 receptors, as the H4 receptor‐specific inverse agonists/antagonist JNJ 7777120, but not ciproxifan, H3 receptor antagonist, dose‐dependently blocked this effect in RBE4 cells.Conclusions and ImplicationsBoth Hrh3 and Hrh4 receptors are expressed in rat brain endothelial cells, and activation of the histamine H4 receptor activates the Erk1/2 cascade. H3 and H4 receptors in endothelial cells are potentially important for regulation of blood–brain barrier permeability, including trafficking of immunocompetent cells.Linked ArticlesThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease
Authors: Iborra M , Bernuzzi F , Correale C , Vetrano S , Fiorino G , Beltrán B , Marabita F , Locati M , Spinelli A , Nos P , Invernizzi P , Danese S 
Published: March 2013

Summary
The altered expression of micro-RNA (miRNA) has been associated with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to establish specific miRNA expression patterns in the serum and mucosa of inflammatory bowel disease (IBD) patients (UC and CD with colonic involvement) at different stages of the disease. Serum and biopsies from nine active CD (aCD), nine inactive CD (iCD), nine active UC (aUC) and nine inactive UC (iUC) and serum from 33 healthy subjects were collected. Up to 700 miRNAs were evaluated by the TaqMan® human miRNA array. The ΔCt values were obtained using the mean expression values of all expressed miRNAs in a given sample as a normalization factor for miRNA real-time quantitative polymerase chain reaction data. The levels of serum miRNAs in CD and UC patients were different to healthy subjects. Thirteen serum miRNAs were expressed commonly in CD and UC patients. Two miRNAs were higher and four miRNAs were lower in the serum of aCD than iCD. No serum miRNA was regulated exclusively in aUC compared with iUC patients. Four miRNAs were higher and three miRNAs were lower in the mucosa of aCD than iCD. Two miRNAs were higher and three miRNAs were lower in the mucosa of aUC than iUC. No serum miRNAs coincided with tissue miRNAs in aCD and aUC patients. Our results suggest the existence of specific miRNA expression patterns associated with IBD and their different stages and support the utility of miRNA as possible biomarkers. This pilot study needs to be validated in a large prospective cohort.
Phylogenetic relationships of Hamadryas (Nymphalidae: Biblidinae) based on the combined analysis of morphological and molecular data
Authors: Garzón‐Orduña Ivonne J. , Marini‐Filho Onildo , Johnson Steve G. , Penz Carla M. 
Published: March 2013

AbstractA new phylogenetic hypothesis for the Neotropical butterfly genus Hamadryas, based on the combination of a morphological matrix, one mitochondrial (COI) and four nuclear markers (CAD, RpS5, EF1a, and Wingless), is presented. Results from analyses of the molecular evidence are compared with a previously published morphological phylogeny. Molecular data and the analysis of the complete dataset support the monophyly of Hamadryas and most sister groups suggested by morphological data alone. The addition of DNA sequences to the morphological matrix helped define species groups for which no morphological synapomorphies were found. Partitioned Bremer support indicates that COI, CAD, and morphology were consistently in agreement with the combined evidence tree. In contrast, signal from the nuclear markers Rps5, EF1a, and Wingless showed indifference at most levels of the tree, and minor conflict at nodes solving the relationships between species groups. Though resolved, the combined evidence tree shows low resample values, particularly among species groups whose relationships were characterized by short internodes. A reassessment about the pattern of character change for sound production is presented and discussed.
M9, A Novel Region of Amino‐Nogo‐A, Attenuates Cerebral Ischemic Injury by Inhibiting NADPH Oxidase‐Derived Superoxide Production in Mice
Authors: Guo Fan , Jin Wei‐Lin , Li Li‐Ya , Song Wen‐Ying , Wang Hui‐Wen , Gou Xing‐Chun , Mi Ya‐Jing , Wang Qiang , Xiong Lize 
Published: March 2013

SummaryAimsIn acute stroke, neurological damage is due to oxidative stress and neuronal apoptotic death. This study investigated whether Nogo‐A 290‐562 residues region (M9), fused to the transduction domain of the HIV trans‐activator (TAT) protein, is neuroprotective against cerebral ischemia and the mechanisms.MethodsTransient focal cerebral ischemia was induced by middle cerebral artery occlusion in male C57BL/6J mice. TAT‐M9, its mutation or vehicle was applied via intraperitoneal injection at the onset of reperfusion. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the ratio of Bax/Bcl‐2 were evaluated. Malondialdehyde (MDA), reactive oxygen species (ROS) levels, and NADPH oxidase activation were measured in the presence or absence of the NADPH oxidase inhibitor apocynin or activator tetrabromocinnamic acid (TBCA).ResultsImmunofluorescence results confirmed that TAT‐M9 was transduced into brain parenchyma, and it significantly improved neurological behavior, reduced infarct volumes, protected neuronal cells from apoptosis, inhibited activation of NADPH oxidase, and decreased MDA and ROS contents. Furthermore, apocynin imitated the beneficial effects of TAT‐M9, while TBCA abolished them.ConclusionsOur results demonstrate that TAT‐M9 administration attenuates cerebral ischemia by inhibiting NADPH oxidase‐mediated oxidative damage and neuronal apoptosis in mice. TAT‐M9 may be a potential treatment for cerebrovascular disease.
Stenting as first‐line management for all patients with nonperforating left‐sided obstructing colorectal cancer
Authors: Warden C. , Stupart D. , Goldberg P. 
Published: March 2013

AbstractAimSince 2005, we have used self‐expanding metal stents (SEMS) as primary treatment for all patients with left‐sided obstructing colorectal cancer without evidence of perforation. The purpose of this study was to assess the safety and efficacy of this treatment.MethodThis was a prospective study of consecutive patients with left‐sided obstructing colorectal cancer without perforation or peritonitis treated between January 2005 and June 2009. SEMS placement was attempted in all cases. Emergency surgery was reserved for patients in whom a stent placement failed. After successful decompression, surgery was offered to patients with potentially curable disease.ResultsSeventy‐seven patients were included, with successful SEMS placement in 60/77 (78%) patients, 25 as a bridge to surgery and 35 for palliation. Immediate complications occurred in two (3%) cases. There was no mortality. Of 35 patients in whom SEMS was for palliation, 32 (91%) avoided surgery altogether. A stoma was fashioned in 5 (8.3%) of the 60 patients who were successfully stented, and in 12 (71%) of the 17 patients in whom stenting failed (P = 0.0001).ConclusionA SEMS‐based management protocol for patients with large bowel obstruction due to colorectal cancer is safe and effective.