bluuebunny/crossref_metadata_2025_split huggingface dataset:
Narrow‐band UVB irradiation stimulates the migration and functional development of vitiligo‐IgG antibodies‐treated pigment cells
Authors: Wu C.‐S. , Lan C.‐C.E. , Yu H.‐S. 
Published: May 2011

AbstractBackground  The pathogenesis of vitiligo remains unclear. Most authorities favoured the autoimmune cause for the strong associations of vitiligo with multiple autoimmune diseases and the presence of autoantibodies in vitiligo patients. Narrow‐band UVB (NBUVB) irradiation has been considered to be an effective treatment for vitiligo with simple treatment procedure and decreased accumulated ultraviolet exposure doses.Objectives  The aim this study was to investigate the effects of NBUVB irradiation on normal IgG antibodies (N‐IgG) or vitiligo IgG antibodies (V‐IgG)‐treated NCCmelan5 cells in terms of proliferation, migration and melanin formation.Methods  Cultured NCCmelan5 cells were treated with (i) NBUVB irradiation alone, (ii) N‐IgG or V‐IgG alone, and (iii) combination of N‐IgG or V‐IgG with NBUVB irradiation. The proliferation of NCCmelan5 cells were evaluated using BrdU incorporation assay. Western blotting was used to determine the expressions of phosphorylated p125FAK (pp125FAK) and tyrosinase in NCCmelan5 cells. The locomotion of NCCmelan5 cells was assessed using time‐lapse assay and in vitro wound scratch assay.Results  Neither N‐IgG nor V‐IgG significantly affected the proliferation of NCCmelan5 cells. The migration, melanin formation and tyrosinase expression in NCCmelan5 cells were decreased by V‐IgG. NBUVB irradiation increased the proliferation of V‐IgG treated NCCmelan5 cells. In addition, NBUVB irradiation enhanced the mobility of V‐IgG‐treated NCCmelan5 cells via upregulation of pp125FAK. The melanogenesis and tyrosinase expression in V‐IgG‐treated NCCmelan5 cells were promoted using NBUVB irradiation.Conclusions  Our study demonstrated that the deleterious effects of V‐IgG in the pathogenesis of vitiligo might be overcome by NBUVB irradiation.
Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation
Authors: Dhein S , Rothe S , Busch A , Rojas Gomez DM , Boldt A , Reutemann A , Seidel T , Salameh A , Pfannmüller B , Rastan A , Kostelka M , Mohr FW 
Published: May 2011

BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF).EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day−1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi‐electrode mapping.KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43‐expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF‐induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol.CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti‐arrythmic drugs.
Paeoniflorin suppresses the expression of intercellular adhesion molecule‐1 (ICAM‐1) in endotoxin‐treated human monocytic cells
Authors: Jin Lei , Zhang Li‐Min , Xie Ke‐Qiang , Ye Yang , Feng Linyin 
Published: May 2011

BACKGROUND AND PURPOSE Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti‐inflammatory property. Abnormally high levels of intercellular adhesion molecule‐1 (ICAM‐1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM‐1 elevated in LPS‐activated differentiated human monocytic U937 cells and TNF‐α‐stimulated human umbilical vein endothelial cells (HUVECs).EXPERIMENTAL APPROACH mRNA levels were evaluated by RT‐PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF‐κB translocation, and NF‐κB binding to nuclear DNA was determined by EMSA.KEY RESULTS PF inhibited ICAM‐1 expression elevated in LPS‐induced U937 cells and TNF‐α‐stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A1 receptors, application of a selective adenosine A1 receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM‐1 expression. PF suppressed the activation of the NF‐κB pathway, which regulates the expression of ICAM‐1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.CONCLUSIONS AND IMPLICATIONS PF inhibits ICAM‐1 expression in LPS‐treated U937 cells and TNF‐α‐stimulated HUVECs by suppressing the activation of the NF‐κB pathway.
5α‐Reduced glucocorticoids exhibit dissociated anti‐inflammatory and metabolic effects
Authors: Yang C , Nixon M , Kenyon CJ , Livingstone DEW , Duffin R , Rossi AG , Walker BR , Andrew R 
Published: May 2011

BACKGROUND AND PURPOSE Dissociating anti‐inflammatory efficacy from the metabolic side effects of glucocorticoids is an attractive therapeutic goal. 5α‐Tetrahydro‐corticosterone (5αTHB), produced from corticosterone by 5α‐reductases, activates glucocorticoid receptors. This study compares the effects of 5αTHB on inflammation and metabolism in vitro and in vivo.METHODS Suppression of cytokine release by 5αTHB and corticosterone were studied following LPS activation of mouse bone marrow derived macrophages. In vivo the efficacy of these steroids to dysregulate metabolic homeostasis and modulate immune suppression and the responses to thioglycollate‐induced peritonitis in C57BL/6 mice were studied following acute injection (1.5–15 mg) and chronic infusion (50 µg·day−1, 14 days).RESULTS In macrophages, 5αTHB increased secretion of IL‐10 similarly to corticosterone (180%, 340%; data are % vehicle, treated with 5αTHB and corticosterone, respectively) and suppressed LPS‐induced secretion of TNF‐α (21.9%, 74.2%) and IL‐6 (16.4%, 69.4%). In mice with thioglycollate‐induced peritonitis, both 5αTHB and corticosterone reduced the numbers of neutrophils (58.6%, 49.9%) and inflammatory monocytes (69.5%, 96.4%), and also suppressed MCP‐1 (48.7%, 80.9%) and IL‐6 (53.5%, 86.7%) in peritoneal exudate. In mice chronically infused with 5αTHB and corticosterone LPS‐induced production of TNF‐α from whole blood was suppressed to the same degree (63.2%, 37.2%). However, in contrast to corticosterone, 5αTHB did not induce body weight loss, increase blood pressure or induce hyperinsulinaemia.CONCLUSIONS 5αTHB has anti‐inflammatory effects in vitro and in vivo. At doses with equivalent anti‐inflammatory efficacy to corticosterone, 5αTHB did not induce metabolic toxicity and thus may be a prototype for a safer anti‐inflammatory drug.
Prognostic value of 18F‐FDG PET for hepatocellular carcinoma patients treated with sorafenib
Authors: Lee Jae Hoon , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Han Kwang‐Hyub , Seo Hyo Jung , Lee Jong Doo , Choi Hye Jin 
Published: May 2011

AbstractBackground: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used 18F‐2‐fluoro‐2‐deoxyglucose (18F‐FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC.Materials and methods: A total of 29 patients with HCC were included. Baseline 18F‐FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient.Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0–12.0] and 3.8 months (95% CI: 1.4–6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α‐fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10; <5.00) and high SUVmax (n=19;≥5.00), the low SUV group showed significantly longer OS and PFS (P=0.023 and P=0.042 respectively).Conclusion: Our study showed that the degree of FDG uptake is an independent prognostic factor in patients with HCC who undergo sorafenib treatment.
Cholesterol: recapitulation of its active role during liver regeneration
Authors: Delgado‐Coello Blanca , Briones‐Orta Marco A. , Macías‐Silva Marina , Mas‐Oliva Jaime 
Published: May 2011

AbstractLiver regeneration is a compensatory hyperplasia produced by several stimuli that promotes proliferation in order to provide recovery of the liver mass and architecture. This process involves complex signalling cascades that receive feedback from autocrine and paracrine pathways, recognized by parenchymal as well as non‐parenchymal cells. Nowadays the dynamic role of lipids in biological processes is widely recognized; however, a systematic analysis of their importance during liver regeneration is still missing. Therefore, in this review we address the role of lipids including the bioactive ones such as sphingolipids, but with special emphasis on cholesterol. Cholesterol is not only considered as a structural component but also as a relevant lipid involved in the control of the intermediate metabolism of different liver cell types such as hepatocytes, hepatic stellate cells and Kupffer cells. Cholesterol plays a significant role at the level of specific membrane domains, as well as modulating the expression of sterol‐dependent proteins. Moreover, several enzymes related to the catabolism of cholesterol and whose activity is down regulated are related to the protection of liver tissue from toxicity during the process of regeneration. This review puts in perspective the necessity to study and understand the basic mechanisms involving lipids during the process of liver regeneration. On the other hand, the knowledge acquired in this area in the past years, can be considered invaluable in order to provide further insights into processes such as general organogenesis and several liver‐related pathologies, including steatosis and fibrosis.
Inflammation in epilepsy: Clinical observations
Authors: Aronica Eleonora , Crino Peter B. 
Published: May 2011

SummaryOver the past decade, an increasing number of observations indicate that activation of inflammatory processes occurs in variety of focal epilepsies. Understanding the feature and consequences of neuroinflammation, including the contribution to development and perpetuation of seizures, as well as to mood or cognitive dysfunction, is a major requisite for delineating its role in epilepsy. The present article discusses the most recent observations supporting the involvement of the inflammatory response in human focal epilepsy. It also evaluates emerging evidence concerning the possibility to identify epilepsy‐associated inflammatory biomarkers in cerebrospinal fluid and serum, as well as the potential application of neuroimaging approaches to study the inflammatory reactions in chronic epilepsy patients in vivo, aiming to improve the recognition of appropriate patient populations who might benefit from antiinflammatory or immunomodulatory therapies.
Molecular cascades that mediate the influence of inflammation on epilepsy
Authors: Friedman Alon , Dingledine Ray 
Published: May 2011

SummaryExperimental evidence strongly indicates a significant role for inflammatory and immune mediators in initiation of seizures and epileptogenesis. Here we will summarize data supporting the involvement of IL‐1β, TNF‐α and toll‐like receptor 4 in seizure generation and the process of epileptogenesis. The physiological homeostasis and control over brain immune response depends on the integrity of the blood‐brain barrier, transforming growth factor (TGF)‐β signaling and leukocyte migration. To what extent targeting the immune system is successful in preventing epileptogenesis, and which signaling pathway should be beleaguered is still under intensive research.
Antiepileptic drugs and the immune system
Authors: Beghi Ettore , Shorvon Simon 
Published: May 2011

SummaryData on the effects of antiepileptic drugs on the immune system are frequently inconsistent and sometimes conflicting because the effects of drugs cannot be separated from those of seizures, first‐generation drugs have been most intensively investigated, the patient’s genetic background, the mechanism of action and the pharmacokinetic profile of AEDs and the concurrent use of immunosuppressant drugs may act as confounders. Valproate, carbamazepine, phenytoin, vigabatrin, levetiracetam, and diazepam have been found to modulate the immune system activity by affecting humoral and cellular immunity. AEDs are associated with pharmacokinetic interactions (most frequently occurring with carbamazepine, phenytoin, phenobarbital and valproate). Hepatic metabolism is the primary site of interaction for both AEDs and immunotherapies (ACTH, dexamethasone, hydrocortisone, methylprednisolone, cyclophosphamide, methotrexate, rituximab), which entail induction or inhibition of drug effects. However, the clinical importance of these drug interactions is still far from defined. An important adverse effect of the action of AEDs on the immune system is antiepileptic hypersensitivity syndrome (AHS), a life‐threatening, idiosyncratic cutaneous reaction to aromatic AEDs resulting in end organ damage. Phenytoin, carbamazepine, phenobarbital, lamotrigine, oxcarbazepine, felbamate, and zonisamide have been implicated. The pathogenic mechanisms of AHS are incompletely understood.
How we treat: transfusion medicine support of obstetric services
Authors: Goodnough Lawrence T. , Daniels Kay , Wong Amy E. , Viele Maurene , Fontaine Magali F. , Butwick Alexander J. 
Published: May 2011

BACKGROUND: Obstetric services depend on the transfusion service (TS) to provide diagnostic testing and blood component therapy for clinical care pathways.STUDY DESIGN AND METHODS: We describe three quality improvement (QI) initiatives implemented to improve TS support of obstetric services.RESULTS: We implemented a pathway for patients requiring an ABO/Rh order for every admission to obstetric services, along with reconciliation of the daily hospital birth manifest and TS umbilical cord log to identify every woman eligible for RhIG. After assessment over 6 months, 21 (1%) of 2041 women lacked an admission ABO/Rh; all subsequently had ABO/Rh determinations. Umbilical cords were missing for eight (0.4%) mothers; four were D− and received RhIG. We developed algorithms for diagnostic blood ordering for patients deemed at “low,”“moderate,” or “high” risk of blood transfusion. A 27% reduction in total diagnostic test volumes and 24% reduction in charges was documented after compared to before implementation. We analyzed the impact of our massive transfusion protocol (MTP) on blood inventory management for 31 (0.25%) women undergoing 12,945 deliveries, representing 11% of 286 MTPs for all clinical services over a 32‐month interval. O− uncrossmatched red blood cells (RBCs) represented 103 (24%) of 421 RBC units issued. Wastage rates of RBCs, plasma, and platelets ordered and issued in the MTPs were 0.7, 16, and 3%, respectively.CONCLUSION: QI initiatives for RhIG prophylaxis, diagnostic blood test ordering, and MTP improve TS support of obstetric services.
Are People Successful at Learning Sequences of Actions on a Perceptual Matching Task?
Authors: Yakushijin Reiko , Jacobs Robert A. 
Published: May 2011

AbstractWe report the results of an experiment in which human subjects were trained to perform a perceptual matching task. Subjects were asked to manipulate comparison objects until they matched target objects using the fewest manipulations possible. An unusual feature of the experimental task is that efficient performance requires an understanding of the hidden or latent causal structure governing the relationships between actions and perceptual outcomes. We use two benchmarks to evaluate the quality of subjects’ learning. One benchmark is based on optimal performance as calculated by a dynamic programming procedure. The other is based on an adaptive computational agent that uses a reinforcement‐learning method known as Q‐learning to learn to perform the task. Our analyses suggest that subjects were successful learners. In particular, they learned to perform the perceptual matching task in a near‐optimal manner (i.e., using a small number of manipulations) at the end of training. Subjects were able to achieve near‐optimal performance because they learned, at least partially, the causal structure underlying the task. In addition, subjects’ performances were broadly consistent with those of model‐based reinforcement‐learning agents that built and used internal models of how their actions influenced the external environment. We hypothesize that people will achieve near‐optimal performances on tasks requiring sequences of action—especially sensorimotor tasks with underlying latent causal structures—when they can detect the effects of their actions on the environment, and when they can represent and reason about these effects using an internal mental model.
Cesarean section after induction of labor compared with expectant management: no added risk from gestational week 39
Authors: RASMUSSEN OLE BREDAHL , RASMUSSEN STEEN 
Published: May 2011

Abstract Objective. To compare induction of labor and expectant management by gestational week with regard to the need for cesarean section (CS) in labor. Design. Cohort study. Setting. National study based on the Danish Birth Registry. Population. Aggregated data from 230 528 deliveries from 2004 until mid‐year 2009. Women with cesarean section before labor, previous cesarean, preterm birth, breech presentation, multiple pregnancy and specified medical illnesses in pregnancy were excluded. Methods. We compared by gestational week nulliparous and parous women who were either induced or had expectant management until later spontaneous or induced labor. For each of five comparisons, we conducted multivariable logistic regression analysis, controlling for body mass index, age, smoking in pregnancy and use of epidural analgesia during labor. Main Outcome Measure. Rate of CS in labor. Results. From gestational week 39 and thereafter, there was no difference with regard to CS rates in labor among nulliparous and parous women when comparing women with induced labor and those women who waited for a later labor, either induced or spontaneous. The odds ratios (with confidence intervals) for CS in labor in nulliparous women were 0.99 (0.84–1.17), 1.16 (1.04–1.30), 1.04 (0.94–1.15), 1.00 (0.92–1.10) and 0.97 (0.88–1.07) for weeks 37–41, respectively. For parous women the corresponding figures were 1.72 (1.35–2.20), 1.27 (1.04–1.55), 1.15 (0.95–1.39), 1.18 (0.99–1.40) and 1.07 (0.87–1.32), respectively. Conclusions. Induction of labor provides a sound tool when counseling a woman either going past term or presenting with a problem, even if it is not a severe medical illness.
Deep pelvic endometriosis negatively affects ovarian reserve and the number of oocytes retrieved for in vitro fertilization
Authors: PAPALEO ENRICO , OTTOLINA JESSICA , VIGANÒ PAOLA , BRIGANTE CLAUDIO , MARSIGLIO ELENA , DE MICHELE FRANCESCA , CANDIANI MASSIMO 
Published: May 2011

Abstract Objective. Endometriosis‐associated infertility results in reduced ovarian response, fewer oocytes available for fertilization, compromised oocyte quality and higher miscarriage rates. A consistent proportion of women with endometriosis require in vitro fertilization. We sought to clarify the impact of deep infiltrating pelvic disease on antral follicle count and ovarian response to follicle‐stimulating hormone (FSH) stimulation in patients with severe endometriosis. Design. Retrospective cohort study. Setting. University hospital. Population. Patients with severe endometriosis (stages III–IV; n=51) were divided into two groups regarding localization of endometriosis during surgical staging: ovarian (n=27) and both ovarian and deep infiltrating disease (n=24). Methods. A total of 73 long‐protocol ovulation induction cycles with recombinant FSH for an intracytoplasmic sperm injection program were given. On day 3 of the cycle, measurements of FSH and luteinizing hormone and an ultrasound evaluation of antral follicle count were performed. Main Outcome Measures. Number of oocytes collected at ovum pick up, number of mature oocytes, number of embryos transferred and clinical pregnancy rate. Results. Ovarian reserve in terms of antral follicle count was damaged in both groups but, if adjusted for age, it was significantly lower in the ovarian and pelvic infiltrating group compared with patients having only ovarian endometriosis. Pelvic deep infiltrating disease significantly impacted on the number of oocytes collected at pick up when adjusted for age. Conclusions. Deep infiltrating pelvic disease can negatively affect ovarian reserve in terms of antral follicle count and number of oocytes retrieved. Mechanisms underlying this phenomenon need to be elucidated.