bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological profile of the clonidine‐induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with α2A/2C‐adrenoceptors
Authors: Villalón C M , Albarrán‐Juárez J A , Lozano‐Cuenca J , Pertz H H , Görnemann T , Centurión D 
Published: February 2008

Background and purpose: Resistance blood vessels are innervated by sympathetic and primary sensory nerves, which modulate vascular tone through the release of noradrenaline and calcitonin gene‐related peptide (CGRP), respectively. Moreover, electrical stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses which are mainly mediated by CGRP release. The present study has investigated the role of α2‐adrenoceptors in the inhibition of these vasodepressor responses.Experimental approach: 144 pithed male Wistar rats were pretreated with hexamethonium (2 mg kg−1 min−1) followed by i.v. continuous infusions of either methoxamine (15 and 30 μg kg−1 min−1) or clonidine (3, 10 and 30 μg kg−1 min−1). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the spinal cord (T9–T12) resulted in frequency‐dependent decreases in diastolic blood pressure.Key results: The infusion of clonidine (10 μg kg−1 min−1), as compared to those of methoxamine (15 or 30 μg kg−1 min−1), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of α‐CGRP (0.1–1 μg kg−1). This inhibition by clonidine was: (i) antagonized by 300 μg kg−1 rauwolscine (α2A/2B/2C), 300 and 1000 μg kg−1 BRL44408 (α2A), or 10 and 30 μg kg−1 MK912 (α2C); and (ii) unaffected by 1 ml kg−1 saline, 100 μg kg−1 BRL44408, 3000 and 10000 μg kg−1 imiloxan (α2B) or 3 μg kg−1 MK912.Conclusions and implications: The inhibition produced by 10 μg kg−1 min−1 clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional α2A/α2C‐adrenoceptors.
A role for the RISK pathway and KATPchannels in pre‐ and post‐conditioning induced by levosimendan in the isolated guinea pig heart
Authors: Du Toit E F , Genis A , Opie L H , Pollesello P , Lochner A 
Published: February 2008

Background and purpose:Myocardial reperfusion injury prevents optimal salvage of the ischaemic myocardium, and adjunct therapy that would significantly reduce reperfusion injury is still lacking. We investigated whether (1) the heart could be pre‐ and/or post‐conditioned using levosimendan (levosimendan pre‐conditioning (LPC) and levosimendan post‐conditioning (LPostC)) and (2) the prosurvival kinases and/or the sarcolemmal or mitochondrial KATPchannels are involved.Experimental approach:Isolated guinea pig hearts were treated with two 5 min cycles of levosimendan (0.1 μM) interspersed with vehicle perfusion, or two 5 min cycles of ischaemia/reperfusion, before coronary artery ligation (CAL) for 40 min at 36.5 °C. Hearts were treated with mitochondrial or sarcolemmal KATPchannel blockers before LPC or LPostC. For post‐conditioning, hearts received three 30 s cycles of ischaemia/reperfusion or levosimendan/vehicle. Hearts were pretreated with levosimendan immediately before CAL (without washout). Cardiac function, infarct size and reperfusion injury salvage kinase activity was assessed.Key results:LPC and LPostC halved the infarct size compared with controls (P<0.05). Treatment with KATPchannel blockers before LPC or LPostC reversed this decrease. Pretreating hearts with levosimendan increased activity of extracellular signal‐regulated kinase (ERK) 42/44 on reperfusion and had the most marked infarct‐lowering effect (P<0.05).Conclusions and implications:(1) Hearts could be pharmacologically pre‐ and post‐conditioned with levosimendan; (2) levosimendan pretreatment is the most effective way to reduce infarct size, possibly by increasing ERK 42/44 activity; (3) benefits of LPC and LPostC were abolished by both KATPchannel blockers and (4) LPC may be useful before elective cardiac surgery, whereas LPostC may be used after acute coronary artery events.
A potent and selective p38 inhibitor protects against bone damage in murine collagen‐induced arthritis: a comparison with neutralization of mouse TNFα
Authors: Mihara K , Almansa C , Smeets R L , Loomans E E M G , Dulos J , Vink P M F , Rooseboom M , Kreutzer H , Cavalcanti F , Boots A M , Nelissen R L 
Published: February 2008

Background and purpose: The p38 kinase regulates the release of proinflammatory cytokines including tumour‐necrosis factor‐α (TNFα) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762‐0, we investigated the therapeutic potential of p38 inhibition and compared this to anti‐mouse (m)TNFα antibody treatment in murine collagen‐induced arthritis (CIA).Experimental approach: Pharmacological profiles of Org 48762‐0 were characterized in kinase assays, cellular assays and in lipopolysaccharide (LPS)‐induced inflammation in mice. The effects of Org 48762‐0 and of mTNFα‐neutralization on established arthritis were examined in murine CIA.Key results: Org 48762‐0 potently inhibited p38α kinase with a high degree of kinase selectivity. In cellular assays, Org 48762‐0 reduced LPS‐induced TNFα release. Oral administration of Org 48762‐0 in mice showed drug‐like pharmacokinetic properties and inhibited LPS‐induced cytokine production. These pharmacological characteristics of Org 48762‐0 prompted a comparison of therapeutic efficacy with mTNFα‐neutralization in CIA. Org 48762‐0 and anti‐mTNFα antibody treatment equally inhibited development of arthritis when evaluated macroscopically. Radiological analyses revealed protection against bone damage for both treatments, although statistical difference was reached with Org 48762‐0 treatment only. Further, micro‐computed tomographical and histopathological analyses confirmed the protective effects of Org 48762‐0 on joint damage.Conclusions and implications: Pharmacological targeting of p38 kinase provided good protection against joint tissue damage in CIA. In our experiments, neutralization of mTNFα produced less prominent suppression of bone damage. Our data suggest a therapeutic potential for selective and potent p38 inhibitors in RA.
Three-dimensional endoluminal ultrasound-guided interstitial brachytherapy in patients with anal cancer
Authors: Christensen A. F. , Nielsen Bachmann M. , Engelholm S. A. 
Published: February 2008

Background: New techniques using image guidance other than computed tomography (CT) and traditional two-dimensional (2D) endosonography might improve interstitial brachytherapy in patients with anal cancer. Purpose: To investigate a new technique guided by three-dimensional (3D) endosonography used in our institution. Material and Methods: Seventeen patients with anal carcinoma were referred to interstitial brachytherapy under 3D endosonographic guidance after external radiotherapy. The procedure was initiated by anal endosonography performed with a 10-MHz rotating endoprobe. Cross-sectional images of the anal sphincters were stored on a 3D system during retraction of the endoprobe through the anal canal. Afterward, any projection could be reconstructed. From this scanning, the optimal positioning of the needles was determined. The needles were inserted through holes in an externally fixated anal template. A repeated endosonography assured that optimal tumor coverage could be obtained by adjusting the number, dwell positions, and/or position of the needles. Results: In all patients, endosonography was able to visualize the extension of the tumors and the position of each needle in 3D. Conclusion: 3D endosonography guidance of interstitial brachytherapy in anal carcinoma seems to optimize the implant procedure and offer better information for dose planning.
The NADPH oxidase Cpnox1 is required for full pathogenicity of the ergot fungus Claviceps purpurea
Authors: GIESBERT SABINE , SCHÜRG TIMO , SCHEELE SANDRA , TUDZYNSKI PAUL 
Published: February 2008

SUMMARYThe role of reactive oxygen species (ROS) in interactions between phytopathogenic fungi and their hosts is well established. An oxidative burst mainly caused by superoxide formation by membrane‐associated NADPH oxidases is an essential element of plant defence reactions. Apart from primary effects, ROS play a major role as a second messenger in host response. Recently, NADPH oxidase (nox)‐encoding genes have been identified in filamentous fungi. Functional analyses have shown that these fungal enzymes are involved in sexual differentiation, and there is growing evidence that they also affect developmental programmes involved in fungus–plant interactions. Here we show that in the biotrophic plant pathogen Claviceps purpurea deletion of the cpnox1 gene, probably encoding an NADPH oxidase, has impact on germination of conidia and pathogenicity: Δcpnox1 mutants can penetrate the host epidermis, but they are impaired in colonization of the plant ovarian tissue. In the few cases where macroscopic signs of infection (honeydew) appear, they are extremely delayed and fully developed sclerotia have never been observed. C. purpurea Nox1 is important for the interaction with its host, probably by directly affecting pathogenic differentiation of the fungus.
Quantitative trait loci for chemical body composition traits in pigs and their positional associations with body tissues, growth and feed intake
Authors: Duthie C. , Simm G. , Doeschl‐Wilson A. , Kalm E. , Knap P. W. , Roehe R. 
Published: February 2008

SummaryIn this study, quantitative trait loci (QTL) for chemical and physical body composition, growth and feed intake in pigs were identified in a three‐generation full‐sib population, developed by crossing Pietrain sires with a commercial dam line. Phenotypic data from 315 F2 animals were available for protein and lipid deposition measured in live animals by the deuterium dilution technique at 30‐, 60‐, 90‐, 120‐ and 140‐kg body weight. At 140‐kg body weight, carcass characteristics were measured by the AutoFOM grading system and after dissection. Three hundred and eighty‐six animals from 49 families were genotyped for 51 molecular markers covering chromosomes SSC2, SSC4, SSC8, SSC9, SSC10 and SSC14. Novel QTL for protein (lipid) content at 60‐kg body weight and protein (lipid) accretion from 120 to 140 kg were detected on SSC9 near several previously detected QTL for lean and fat tissue in neck, shoulder and ham cuts. Another QTL for lipid accretion was found on SSC8, closely associated with a QTL for intramuscular fat content. QTL for daily feed intake were detected on SSC2 and SSC10. The favourable allele of a QTL for food conversion ratio (FCR) on SSC2 was associated with alleles for increased lean tissue and decreased fat tissue. Because no QTL for growth rate were found in the region, the QTL for FCR is most likely due to a change in body composition. These QTL provide insights into the genomic regulation of chemical or physical body composition and its association with feed intake, feed efficiency and growth.
Characterization of peptidic and carbohydrate cross‐reactive determinants in pollen polysensitization
Authors: Chardin H. , Sénéchal H. , Wal J. M. , Desvaux F. X. , Godfrin D. , Peltre G. 
Published: February 2008

SummaryBackground
Cross‐reactivity may be due to protein sequence or domain homologies and/or the existence of cross‐reactive carbohydrate determinants (CCDs). The clinical relevance of peptidic cross‐reactivities is well known, whereas that of CCDs is still a question of debate. The aim of this study is to characterize the IgE specificity of various patients suffering from pollen polysensitization to identify both peptidic and carbohydrate cross‐reactive determinants.Material and methods
Rapeseed, grass and Arabidopsis proteins were separated by isoelectric focusing, followed by SDS‐PAGE, and transferred to a nitrocellulose sheet. The sheets were incubated either with an individual serum from a birch+grass‐sensitive patient, followed by anti‐human IgE, or with labelled Concanavalin A (ConA). Binding inhibition was tested by incubation of the sera with a mixture of sugar residues.Results
The results showed two different patterns of cross‐reacting sera: a pattern that implies few proteins, not always glycosylated and known as allergens, and a pattern that implies numerous proteins with molecular masses over 30 kDa. This second pattern was very close to the ConA ‐binding pattern. The IgE binding was abolished by pre‐incubation with sugar residues only in the case of the second pattern.Discussion
This study shows that multiple pollen sensitizations could result from multiple sensitizations to specific proteins or from a cross‐sensitization to a wide range of glycoproteins. Two‐D blots allow to characterize a cross‐sensitization due to carbohydrate determinants, and thus to improve the diagnosis of allergy and its medical treatment.
Clinical and immunologic findings of methylene diphenyl diisocyanate‐induced occupational asthma in a car upholstery factory
Authors: Hur G‐Y. , Koh D‐H. , Choi G‐S. , Park H‐J. , Choi S‐J. , Ye Y‐M. , Kim K‐S. , Park H‐S. 
Published: February 2008

SummaryBackground
Although methylene diphenyl diisocyanate (MDI) is widely used in many industries, there have been few immunological studies of MDI‐induced occupational asthma.Objectives
We investigated the effects of MDI exposure on the clinical and immunologic condition of workers in a single car upholstery factory.Methods
Fifty‐eight MDI‐exposed workers were studied. Work‐related lower‐respiratory symptoms (WRRS) were identified using a questionnaire. Serum‐specific IgE and IgG antibodies to MDI‐human serum albumin conjugate were detected by ELISA. Atopy was evaluated using a skin prick test. MDI‐induced occupational asthma was confirmed in the symptomatic workers with a positive result on an MDI‐specific inhalation test.Results
Thirteen (22.4%) of the subjects complained of WRRS. MDI‐induced occupational asthma was confirmed in five (8.6%) of the workers, and occupational eosinophilic bronchitis was confirmed in two (3.5%). The prevalence of specific IgG antibodies (20.7%) was higher than that of specific IgE antibodies (8.6%). The prevalence of MDI‐induced occupational asthma/eosinophilic bronchitis was strongly associated with the presence of both WRRS and serum‐specific IgG antibodies to an MDI‐human serum albumin conjugate (P<0.01, <0.05, respectively).Conclusion
These findings suggest that MDI could be a causative agent of occupational asthma among MDI‐exposed workers. The prevalence of MDI‐induced occupational asthma was 8.6%, and MDI‐induced eosinophilic bronchitis was confirmed in two workers. The presence of work‐related lower‐respiratory symptoms and serum‐specific IgG antibodies to an MDI‐human serum albumin conjugate may be used to predict MDI‐induced occupational asthma/eosinophilic bronchitis in MDI‐exposed workers.
Early skin sensitization to aeroallergens
Authors: De Bilderling G. , Mathot M. , Agustsson S. , Tuerlinckx D. , Jamart J. , Bodart E. 
Published: February 2008

SummaryBackground
Early detection of aeroallergen sensitization is important as a prognosis factor but may be more difficult in young children.Objective
We sought to demonstrate that skin sensitization to aeroallergens was present in a selected group of 0–2‐year‐old children and that it was associated with environmental exposure and a family history of allergic disease.Methods
Data on exposure and history were extracted from the files of 824 children seen in the asthma clinic and who were skin tested to a panel of aero‐ and food allergens.Results
Forty percent of our children demonstrated atopy, 28% were sensitized to aeroallergens, the majority of which to house dust mite. Higher sensitization rates were found in children with large weals to histamine (P<0.001) and in those who slept with soft toys [odds ratio (OR) 1.45, 95% confidence interval (CI) 1.02–2.08]. With a definition of sensitization including the size of the weal to histamine, there was a negative association with a personal history of eczema only (OR 0.66, 95% CI 0.45–0.99). There was no gender‐dependent effect and no association with day‐care attendance.Conclusion
This is one of the largest studies to evaluate skin testing in a selected population of young children. We found a high prevalence of sensitization to aeroallergens, which was associated with exposure to soft toys. Further follow‐up of this population will allow assessment of the predictive value of this sensitization.
Exhaled breath condensate in patients with asthma: implications for application in clinical practice
Authors: Kostikas K. , Koutsokera A. , Papiris S. , Gourgoulianis K. I. , Loukides S. 
Published: February 2008

SummaryExhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non‐invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on‐site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO2, sample de‐aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non‐invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.
Incorporating life histories and diet quality in stable isotope interpretations of crustacean zooplankton
Authors: VENTURA MARC , CATALAN JORDI 
Published: February 2008

Summary1. Stable isotope studies have been extremely useful for improving general food web descriptions due to their ability to simultaneously summarize complex trophic networks and track the energy flow through them. However, when considering trophic relationships involving only two or few species, application of general isotopic interpretations based on average fractionation values may easily lead to misleading conclusions. In these cases a more accurate consideration of the current processes involved in the isotopic fractionation should be considered.2. We investigated the trophic relationships of the crustacean zooplankton assemblage in an alpine lake (Lake Redon, Pyrenees) by means of stable isotopes of carbon and nitrogen and applied information on their life history and biochemical composition in the interpretation.3. The three species occurring in the lake had distinct isotopic signatures: the two copepod species (the cyclopoid Cyclops abyssorum and the calanoid Diaptomus cyaneus) had higher nitrogen isotopic composition than the cladoceran (Daphnia pulicaria), indicative of a higher trophic position of the two copepods. Most intra‐specific isotopic variability was associated with growth, while the effect of metabolic turnover was negligible. The effects of changes in the proportion of lipids was restricted to the adults of the two copepods.4. Daphnia Juveniles showed ontogenetic shifts in their carbon, and nitrogen isotopic composition. Cyclops copepodites only showed changes in carbon isotopic composition. These isotopic shifts with changes in size were the result of: (i) the prevalence of growth over metabolic turnover as the main factor for isotopic variability and (ii) feeding, during the growth period, on isotopically depleted food in the case of Daphnia, and on isotopically enriched food in the case of Cyclops.5. The carbon isotopic variation in Cyclops juveniles could be explained by fitting an isotopic growth model that considered that they fed entirely on Daphnia. However this was not the case for nitrogen isotopic variability. Cyclops nitrogen isotopic composition variation and the Cyclops to Daphnia nitrogen isotopic enrichment were closely correlated to the quantity of Daphnia protein and to the dissimilarity in the essential amino acid composition between the two species, which can be interpreted as an indication of consumer nitrogen limitation.
Expression of TNF‐receptor associated factor 2 correlates with poor progression‐free survival time in ABC‐like primary nodal diffuse large B‐cell lymphomas
Authors: Van Galen J C , Muris J J F , Giroth C P E , Vos W , Ossenkoppele G J , Meijer C J L M , Oudejans J J 
Published: February 2008

Aims:  Tumour necrosis factor (TNF)‐receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)‐κB activation, which is characteristic of in vitro activated B‐cell (ABC)‐like diffuse large B‐cell lymphomas (DLBCL) and may result in expression of anti‐apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti‐apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC‐like DLBCL, and whether expression correlates with clinical outcome.Methods and results:  TRAF2 was expressed in nine of 20 tested ABC‐like DLBCLs and in only one of 13 tested germinal centre B‐lymphocyte (GCB)‐like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression‐free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC‐like DLBCL only, TRAF2 expression was significantly associated with poor progression‐free survival time.Conclusions:  TRAF2 might be involved in activation of NF‐κB in a subset of ABC‐like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.
Near‐field optical images of subwavelength annular aperture arrays exhibiting an extraordinary transmission
Authors: POUJET Y. , SALVI J. , BAIDA F. I. , VAN LABEKE D. , PERENTES A. , SANTSCHI C. , HOFFMANN P. 
Published: February 2008

SummaryIn this paper, we present near‐field optical images of nanostructures exhibiting an extraordinary transmission. These structures consist of annular aperture arrays engraved in a metallic film: they are quite promising structures for nanophotonics because of their high transmission directly linked to a guided mode mediated by each annular aperture. We first briefly explain our fabrication process (focused ion beam milling), then we expose the experimental setup of the near‐field optical microscope working both in reflection and transmission modes. For the reflection mode, the ‘coffee‐bean’ structure of the electromagnetic field predicted by the theory has been quite well reproduced. For the transmission mode, we present preliminary experimental results concerning the influence of the wavelength and the polarization of the incident beam on the obtained near‐field images.