bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of peripheral purinoceptors in the development of bee venom‐induced nociception: A behavioural and electrophysiological study in rats
Authors: Li Li , Luo Rong , Fan Pei , Guo Yuan , Wang Hui‐sheng , Ma Shao‐jie , Zhao Yan 
Published: August 2014

SummaryColocalization of purinergic P2X and P2Y receptors in dorsal root ganglion sensory neurons implies that these receptors play an integrative role in the nociceptive transmission process under inflammatory conditions. In the present study, behavioural and in vivo electrophysiological methods were used to examine the peripheral role of P2 receptors in the persistent nociceptive responses induced by subcutaneous bee venom injection (2 mg/mL) in. Sprague‐Dawley rats Local pretreatment with the wide‐spectrum P2 receptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS; 1 mmol/L, 50 μL) 10 min prior to s.c. bee venom injection significantly suppressed the duration of spontaneous nociceptive lifting/licking behaviour, inhibited mechanical hyperalgesia and decreased the firing of spinal dorsal horn wide dynamic range neurons in response to bee venom, without affecting primary thermal and mirror‐image hyperalgesia. The localized antinociceptive action of PPADS was not due to a systemic effect, because application of the same dose of PPADS to the contralateral side was not effective. The results suggest that activation of peripheral P2 receptors is involved in the induction of nociceptive responses, mechanical hyperalgesia and the excitation of sensory spinal neurons.
CYP2C19*17 increases clopidogrel‐mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel
Authors: Pedersen Rasmus Steen , Nielsen Flemming , Stage Tore Bjerregaard , Vinholt Pernille Just , el Achwah Alaa Bilal , Damkier Per , Brosen Kim 
Published: August 2014

SummaryThe aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open‐label two‐phase cross‐over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi‐Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and its metabolites cycloguanil and 4‐chlorphenylbiguanide (4‐CPB) were determined in 29 of 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant correlations were found between the area under the time–concentration curve (AUC0–∞) of CAMD and both the absolute ADP‐induced P2Y12 receptor‐activated platelet aggregation (r = −0.60, P = 0.0007) and the percentage inhibition of aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the absolute ADP‐induced P2Y12 receptor‐activated platelet aggregation, exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4‐CPB exhibited any significant differences among the genotype groups. In conclusion, carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet aggregation, but do not have significantly lower absolute P2Y12 receptor‐activated platelet aggregation or higher exposure to the active metabolite after a single oral administration of 600 mg clopidogrel.
A case of abatacept associated neutrophilic dermatosis and a review of the literature
Authors: Tiwari Shevya Manjri , Wood Benjamin A , Skender‐Kalnenas Theresa , Cook Nicola 
Published: August 2014

AbstractAbatacept is a novel biological agent that dampens the immune response by blocking the co‐stimulation of T‐cells, thus downregulating T‐cell activation. It is currently approved for the treatment of rheumatoid arthritis (RA). The group of novel immunomodulatory agents, referred to as biologics, have now been used extensively, with established safety and side‐effect profiles. There are, however, increasing reports of adverse paradoxical reactions, most notably resulting from anti‐tumour necrosis factor (TNF) therapy. While cutaneous adverse reactions to abatacept are rare, there are a few reports of such paradoxical reactions. We report a case of an idiosyncratic paradoxical neutrophilic dermatosis associated with the use of abatacept.
Influences of Age, Gender, and Circadian Rhythm on Deceleration Capacity in Subjects without Evident Heart Diseases
Authors: Zhao Ruifu , Li Dan , Zuo Ping , Bai Rong , Zhou Qiang , Fan Jingjing , Li Chengpeng , Wang Lin , Yang Xiaoyun 
Published: August 2014

BackgroundDeceleration capacity (DC) is a newly found predictor of mortality after myocardial infarction. Age‐, gender‐, and circadian rhythm–related differences in DC may limit its predictive value, which should be considered in clinical settings.MethodsDC, average heart rate, and HRV parameters, including 24 hours, awaking state (15:00–20:00) and sleeping mode (00:00–05:00) strips from 24 hours Holter recordings in 636 subjects without heart diseases were examined. Heart rate variability was analyzed in time domains (standard deviation of all normal‐to‐normal intervals [SDNN], normal‐to‐normal RR intervals in all 5‐minute segments [SDANN], and root mean square successive difference [RMSSD]).ResultsThe DC, SDNN, SDANN, RMSSD, and heart rate decreased with age. Deceleration capacity was significantly lower in patients greater than 50 years of age. The largest decrease of SDNN, SDANN, and RMSSD occurred in patients 30–39 years of age. The values of SDNN, SDANN, and DC of women were lower than that of men in the young and middle‐aged groups, but age‐related decrease of DC in men was greater than that in women. Heart rate of women was significantly higher than that of men in younger subjects, especially in a sleeping mode. There were higher values of DC and RMSSD during sleeping than that during a waking state.ConclusionsThe age, gender, and circadian rhythm may be useful when evaluating cardiac autonomic function and need to be considered when evaluating DC and HRV in clinical and scientific researches.
Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent pelvic cancer
Authors: Turner Greg A. , Harris Craig A. , Eglinton Tim W. , Wakeman Chris J. , Kueppers Frank , Dixon Liane , Dobbs Bruce R. , Frizelle Frank A. 
Published: August 2014

AbstractBackgroundThere is minimal published data evaluating the oncological outcome of rectal resection with prostatectomy alone versus rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer. This study aims to evaluate the oncological and functional outcomes of performing rectal resection with prostatectomy alone compared with rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration.MethodsConsecutive patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer between 1998 and 2012 were identified from a prospectively maintained database. Patients undergoing rectal resection with prostatectomy alone were compared with a control group who underwent rectal resection with cystoprostatectomy and urostomy formation. The primary outcome was overall survival. Secondary outcomes analysed in the prostatectomy group included completeness of resection, continence and erectile function.ResultsEleven rectal resections with prostatectomy were compared with 20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and 65% respectively. There was no difference in overall survival (P = 0.40). Urinary continence was achieved in 36% of prostatectomy alone patients, while 27% experienced mild incontinence. Erectile function was poor, with only one patient able to maintain normal erections.ConclusionIn appropriately selected patients with invasive pelvic tumours, rectal resection with prostatectomy alone provides adequate oncological outcomes. The ability to achieve an R0 resection was not compromised and overall survival is comparable with cystoprostatectomy. Urinary function is reasonable in most patients, although sexual function is compromised in almost all.
Optical coherence tomography‐based retinal vessel analysis for the evaluation of hypertensive vasculopathy
Authors: Schuster Alexander Karl‐Georg , Fischer Joachim Ernst , Vossmerbaeumer Christine , Vossmerbaeumer Urs 
Published: August 2014

AbstractPurposeEvaluation of retinal vessels in cardiovascular disease traditionally relies upon funduscopy, but more recently digital photo analysis has expanded the spectrum. As spectral domain optical coherence tomography (OCT) allows an in‐vivo assessment of retinal tissue and its vessels on a histological scale, our study aimed at using this tool for the analysis of the retinal vasculature.MethodsCircumferential peripapillary OCT scans (3DOCT‐2000; Topcon Inc., Tokyo, Japan), with centration on the optic nerve head, were taken from 20 eyes (20 participants) with normal blood pressure and 20 eyes (20 participants) with arterial hypertension above 120 mmHg (mean blood pressure). The diameter of all vessels intersecting the scan line was measured in the OCT and used to calculate central vessel equivalents, and the A/V ratios were calculated. Bland‐Altman analysis was performed to evaluate reliability. Correlation coefficients were determined for reliability of the method as well as with the individual mean arterial blood pressures.ResultsForty eyes (40 participants) were included in the study. Mean arterial blood pressure was 96 ± 4 mmHg in the control group and 132 ± 7 mmHg in the hypertonic group. Mean A/V ratio as determined from OCT scans was 0.82 ± 0.13 (normotonic) versus 0.62 ± 0.11 (hypertonic). A Pearson's correlation coefficient of 0.67 (p < 0.001) was determined between A/V ratio and blood pressure.ConclusionsOur results highlight the feasibility of retinal vessel measurements in spectral domain OCT. A relation between mean arterial blood pressure and OCT‐based A/V ratio was established. Further research will elucidate influencing factors and provide a broader basis for therapeutic approaches.
Graft rejection and failure following endothelial keratoplasty (DSAEK) and penetrating keratoplasty for secondary endothelial failure
Authors: Pedersen Iben B. , Ivarsen Anders , Hjortdal Jesper 
Published: August 2014

AbstractPurposeTo compare the frequency of rejection and graft failure after Descemet's stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for secondary endothelial failure.MethodsSeventy‐eight eyes undergoing DSAEK from 2006 to 2013 and 80 eyes undergoing PK from 1998 to 2013 were included. Indications were endothelial failure due to pseudophakic bullous keratopathy (82%), previous eye trauma (8%), uveitis (4%) or other causes (6%). Rejection episodes and graft failure were recorded, together with preoperative risk factors (glaucoma, neovascularization and active inflammation). Kaplan–Meier survival curves with up to 4 years follow‐up were used to compare DSAEK with PK, as well as low‐risk with high‐risk eyes.ResultsDuring follow‐up, 15% of the PK‐treated eyes and 4% of the DSAEK‐treated eyes experienced rejection. Graft failure occurred in 8% of the PK‐treated eyes and in 7% of the DSAEK‐treated eyes. No significant differences were found in the rate of rejection (p = 0.11), graft failure (p = 0.29) or rejection‐related graft failure (p = 0.30) between DSAEK and PK in low‐risk eyes. In DSAEK, high‐risk eyes (mainly with glaucoma) experienced significantly more rejection episodes (p = 0.01), graft failures (p = 0.04) and rejection‐related graft failures (p = 0.04) compared with low‐risk eyes. No differences were seen between high‐risk and low‐risk PK‐treated eyes (p > 0.40).ConclusionIn the present, relatively small study, no differences in rejection rate or graft failure were found between DSAEK and PK in low‐risk eyes. However, glaucoma seems to increase the risk of graft complications after DSAEK for secondary endothelial failure. Long‐term studies of larger samples sizes are needed to confirm this.
Lack of association of LOXL1 gene variants in Japanese patients with central retinal vein occlusion without clinically detectable pseudoexfoliation material deposits
Authors: Tanito Masaki , Hara Katsunori , Akahori Masakazu , Harata Ayano , Itabashi Takeshi , Takai Yasuyuki , Kaidzu Sachiko , Ohira Akihiro , Iwata Takeshi 
Published: August 2014

AbstractPurposeA possible association has been reported between exfoliation syndrome (EX) and various ocular and systemic vascular disorders; however, it is unclear if there is an association between EX and central retinal vein occlusion (CRVO). Because latent deposits of exfoliation materials might not be recognized during slit‐lamp examination, an ocular biopsy is required to establish a precise diagnosis. We evaluated a possible association between EX and CRVO using lysyl oxidase‐like 1 (LOXL1) gene variants as alternative markers for EX.MethodsThe allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942, and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15 with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX−)] and 90 control patients with cataract without EX (CT).ResultsThe frequencies of the rs1048661 and rs3825942 variants showed borderline difference between the CRVO and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic frequencies). Compared with the CT group, subgroup analysis showed that the CRVO EX+ group had significant differences in the allelic and genotypic frequencies of rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403 and p = 0.07341, respectively), while the CRVO EX− group did not (p = 0.1324–0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not differ between the CRVO and CT groups.ConclusionsWhen the LOXL1 variants were used as disease markers for clinically undetectable EX, there was no association between CRVO and EX. The results suggested that the LOXL1 variants, which are well‐established markers for EX, are not likely genetic markers for CRVO in Japanese subjects.
Serum regenerating islet‐derived 3‐alpha is a biomarker of mucosal enteropathies
Authors: Marafini I. , Di Sabatino A. , Zorzi F. , Monteleone I. , Sedda S. , Cupi M. L. , Antenucci C. , Biancheri P. , Giuffrida P. , Di Stefano M. , Corazza G. R. , Pallone F. , Monteleone G. 
Published: August 2014

SummaryBackgroundThe clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time‐consuming procedures to make a final diagnosis. Regenerating islet‐derived 3‐alpha (Reg3α) is detectable in the circulation of patients with intestinal graft‐versus host disease and patients with inflammatory bowel disease (IBD).AimTo determine whether serum Reg3α testing is useful for discriminating mucosal enteropathies from functional intestinal disorders.MethodsWe prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)‐related diarrhoea. Sera were also taken from 10 CD patients before and after 6–12 months of a gluten‐free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut‐off value. Reg3α levels were measured by a commercial ELISA kit.ResultsLevels of Reg3α exceeded the cut‐off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC patients and one patient with IBS(4%). Reg3α levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3α levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX.ConclusionReg3α is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies.
Quantification of clonal circulating plasma cells in relapsed multiple myeloma
Authors: Gonsalves Wilson I. , Morice William G. , Rajkumar Vincent , Gupta Vinay , Timm Michael M. , Dispenzieri Angela , Buadi Francis K. , Lacy Martha Q. , Singh Preet P. , Kapoor Prashant , Gertz Morie A. , Kumar Shaji K. 
Published: August 2014

SummaryThe presence of clonal circulating plasma cells (cPCs) remains a marker of high‐risk disease in newly diagnosed multiple myeloma (MM) patients. However, its prognostic utility in MM patients with previously treated disease is unknown. We studied 647 consecutive patients with previously treated MM seen at the Mayo Clinic, Rochester who had their peripheral blood evaluated for cPCs by multi‐parameter flow cytometry. Of these patients, 145 had actively relapsing disease while the remaining 502 had disease that was in a plateau and included 68 patients in complete remission (CR) and 434 patients with stable disease. Patients with actively relapsing disease were more likely to have clonal cPCs than those in a plateau (P < 0·001). None of the patients in CR had any clonal cPCs detected. Among patients whose disease was in a plateau, the presence of clonal cPCs predicted for a worse median survival (22 months vs. not reached; P = 0·004). Among actively relapsing patients, the presence of ≥100 cPCs predicted for a worse survival after flow cytometry analysis (12 months vs. 33 months; P < 0·001). Future studies are needed to determine the role of these findings in developing a risk‐adapted treatment approach in MM patients with actively relapsing disease.
A distinct immunogenic region of glutamic acid decarboxylase 65 is naturally processed and presented by human islet cells to cytotoxic CD8 T cells
Authors: Knight R R , Dolton G , Kronenberg-Versteeg D , Eichmann M , Zhao M , Huang G C , Beck K , Cole D K , Sewell A K , Skowera A , Peakman M 
Published: August 2014

Summary
CD8 T cells specific for islet autoantigens are major effectors of β cell damage in type 1 diabetes, and measurement of their number and functional characteristics in blood represent potentially important disease biomarkers. CD8 T cell reactivity against glutamic acid decarboxylase 65 (GAD65) in HLA-A*0201 subjects has been reported to focus on an immunogenic region 114–123 (VMNILLQYVV), with studies demonstrating both 114–123 and 114–122 epitopes being targeted. However, the fine specificity of this response is unclear and the key question as to which epitope(s) β cells naturally process and present and, therefore, the pathogenic potential of CD8 T cells with different specificities within this region has not been addressed. We generated human leucocyte antigen (HLA)-A*0201-restricted CD8 T cell clones recognizing either 114–122 alone or both 114–122 and 114–123. Both clone types show potent and comparable effector functions (cytokine and chemokine secretion) and killing of indicator target cells externally pulsed with cognate peptide. However, only clones recognizing 114–123 kill target cells transfected with HLA-A*0201 and GAD2 and HLA-A*0201+ human islet cells. We conclude that the endogenous pathway of antigen processing by HLA-A*0201-expressing cells generates GAD65114–123 as the predominant epitope in this region. These studies highlight the importance of understanding β cell epitope presentation in the design of immune monitoring for potentially pathogenic CD8 T cells.
Pathophysiology of blast‐induced ocular trauma in rats after repeated exposure to low‐level blast overpressure
Authors: Choi Jae Hyek , Greene Whitney A , Johnson Anthony J , Chavko Mikulas , Cleland Jeffery M , McCarron Richard M , Wang Heuy‐Ching 
Published: August 2014

AbstractBackgroundThe incidence of blast‐induced ocular injury has dramatically increased due to advances in weaponry and military tactics. A single exposure to blast overpressure (BOP) has been shown to cause damage to the eye in animal models; however, on the battlefield, military personnel are exposed to BOP multiple times. The effects of repeated exposures to BOP on ocular tissues have not been investigated. The purpose of this study is to characterize the effects of single or repeated exposure on ocular tissues.MethodsA compressed air shock tube was used to deliver 70 ± 7 KPa BOP to rats, once (single blast overpressure [SBOP]) or once daily for 5 days (repeated blast overpressure [RBOP]). Immunohistochemistry was performed to characterize the pathophysiology of ocular injuries induced by SBOP and RBOP. Apoptosis was determined by quantification activated caspase 3. Gliosis was examined by detection of glial fibrillary acidic protein (GFAP). Inflammation was examined by detection of CD68.ResultsActivated caspase 3 was detected in ocular tissues from all animals subjected to BOP, while those exposed to RBOP had more activated caspase 3 in the optic nerve than those exposed to SBOP. GFAP was detected in the retinas from all animals subjected to BOP. CD68 was detected in optic nerves from all animals exposed to BOP.ConclusionSBOP and RBOP induced retinal damage. RBOP caused more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and increased inflammation in the optic nerve.
Façade to Street to Façade: Negotiating Public Spatial Legality in a World Heritage City
Authors: LITTLE WALTER E. 
Published: August 2014

AbstractAll UNESCO urban World Heritage sites are strictly regulated. In Antigua, Guatemala, this includes building façades and streets, as well as the use of public places. Homeowners and building owners, however, challenge regulations by using unapproved paints, signs, and building materials. Residents modify building façades to accommodate cars and open walls to effectively blend home‐based businesses with the street. At the same time, street vendors contest regulated public spaces by behaving inappropriately by selling goods on public streets rather than designated marketplaces. Rather than conceive of property owners and vendors behavior as outside and in contrast to the building and street vending regulations, I reframe their actions within what I am calling urban spatial permissiveness, a concept I derive from Roy's (2004) theory of the unmapping—flexible regulation—of urban space. Antigua offers an ethnographic setting that shows how regulations are not always rigidly enforced but are negotiated to deal with everyday contingencies that relate to residents' and vendors' rights to the city (Harvey 2008). By way of conclusion I consider Foucault's concept of governmentality as a negotiated process, in order to argue that relationships between building regulations and public space usage reveal the limits of legality and strict enforcement policies.