bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels
Authors: Moran Yehu , Kahn Roy , Cohen Lior , Gur Maya , Karbat Izhar , Gordon Dalia , Gurevitz Michael 
Published: November 2007

Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Navs (voltage-gated Na+ channels) like the structurally dissimilar scorpion α-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Navs, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65±0.46 pmol/100 mg), to compete well with the site-3 toxin LqhαIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (Ki=21.4±7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNav1, but not that of mammalian Navs expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion β-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNav1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.
Contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud's disease
Authors: EASTER Melanie J. , MARSHALL Janice M. 
Published: November 2007

In 15 women with PR (primary Raynaud's) disease and in 15 matched control women, ACh (acetylcholine) was delivered by iontophoresis to the dorsum of the finger (seven 20 s pulses of 0.1 mA, followed by one 20 s pulse of 0.2 mA, applied at 60 s intervals). Cutaneous RCF (red cell flux) was recorded from the same site by the laser Doppler technique. ACh evoked progressive increases in RCF that were comparable in pre- and post-menopausal women with PR [maxima of 294±113 and 259±59 pu (perfusion units) respectively, n=7 and 8 respectively], and in pre-menopausal controls (225±92 pu, n=7), but smaller in post-menopausal controls (140±63 pu, n=8; P&lt;0.05). Aspirin (600 mg, orally), a COX (cyclo-oxygenase) inhibitor, potentiated the ACh-evoked dilator responses in pre- and post-menopausal women with PR (343±129 and 311±48 pu respectively) and post-menopausal controls (277±124 pu; P&lt;0.05), but had no effect in pre-menopausal controls (225±92 pu). These results suggest that vasoconstrictor COX products limit ACh-evoked endothelium-dependent cutaneous dilatation in the digits in pre- and post-menopausal women with PR and in post-menopausal, but not pre-menopausal, control women. We propose that PR disease is associated with abnormality in the ability of oestrogen to modulate the synthesis of endothelium-dependent vasodilator and/or vasoconstrictor COX products.
Prognostic potential of brain natriuretic peptide (BNP) in predialysis chronic kidney disease patients
Authors: CARR Susan J. , BAVANANDAN Sunita , FENTUM Barbara , NG Leong 
Published: November 2007

In the present study, we investigated the potential of N-BNP (N-terminal B-type natriuretic peptide) as a prognostic marker for risk of CV (cardiovascular) events, overall mortality and progression to ESRD (end-stage renal disease) in a cohort of 83 pre-dialysis CKD (chronic kidney disease) patients without clinical evidence of heart failure. During the study, ten patients reached the combined end point of overall mortality and/or CV event. Univariate factors associated with the combined end point were plasma N-BNP (P&lt;0.0005), creatinine (P&lt;0.002), systolic blood pressure (P&lt;0.009) and age (P&lt;0.015). N-BNP levels were higher in patients with CV events (P&lt;0.0005). Cox model regression analysis yielded log10 N-BNP (hazard ratio, 9.608; P&lt;0.007) and pre-existing CV disease (hazard ratio, 4.571; P&lt;0.029) as independent predictors of overall mortality or CV events. Kaplan–Meier analysis curves for the subgroup with supramedian creatinine levels (225 μmol/l) showed significant separation of the curves stratified for plasma N-BNP levels above and below the group median (291 pmol/l) for all end points. Receiver-operator-characteristic curves for N-BNP (355 pmol/l cut-off) demonstrated a specificity of 65.8% at a sensitivity of 100% for predicting CV events/overall mortality. The measurement of plasma N-BNP may aid in the risk stratification of pre-dialysis CKD patients. The high sensitivity and negative predictive value (100%) may enable the selection of patients who could safely be excluded from further investigations, resulting in better focusing of resources.
Opposite changes in carotid versus aortic stiffness during healthy human pregnancy
Authors: MERSICH Beatrix , RIGÓ János , BESENYEI Csilla , LÉNÁRD Zsuzsanna , STUDINGER Péter , KOLLAI Márk 
Published: November 2007

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index β, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8±0.2 versus 2.9±0.3 mmHg for Einc), which was reversed after delivery (2.3±0.2 mmHg). Aortic PWV decreased during pregnancy (6.2±0.2 versus 5.4±0.2 m/s) and increased in the PP period (6.7±0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.
Biodistribution, plasma kinetics and quantification of single-pass pulmonary clearance of adrenomedullin
Authors: DUPUIS Jocelyn , CARON Alexandre , RUËL Nathalie 
Published: November 2007

The biodistribution, pharmacokinetics and multi-organ clearance of the vasodilator peptide AM (adrenomedullin) were evaluated in rats and its single-pass pulmonary clearance was measured in dogs by the indicator-dilution technique. Intravenously administered 125I-rAM(1–50) [rat AM(1–50)] was rapidly cleared following a two-compartment model with a very rapid distribution half-life of 2.0 min [95% CI (confidence interval), 1.98–2.01] and an elimination half-life of 15.9 min (95% CI, 15.0–16.9). The lungs retained most of the injected activity with evidence of single-pass clearance, since retention was lower after intra-arterial (13.5±0.6%) compared with intravenous (30.4±1.5%; P&lt;0.001) injection. Lung tissue levels of total endogenous AM were 20-fold higher than in other organs with no difference in plasma levels across the pulmonary circulation. In dogs, there was 36.4±2.1% first-pass unidirectional extraction of 125I-rAM(1–50) by the lungs that was reduced to 21.9±2.4% after the administration of unlabelled rAM(1–50) (P&lt;0.01). Extraction was not affected by calcitonin-gene-related peptide administration (40.6±2.9%), but was slightly reduced by the C-terminal fragment of human AM(22–52) (31.4±3.3%; P&lt;0.01). These data demonstrate that the lungs are a primary site for AM clearance in vivo with approx. 36% first-pass extraction through specific receptors. This suggests that the lungs not only modulate circulating levels of this peptide, but also represent its primary target.
Different contribution of interleukin-6 and cortisol activity to total plasma fibrin concentration and to acute mental stress-induced fibrin formation
Authors: von KÄNEL Roland , KUDIELKA Brigitte M. , HANEBUTH Dirk , PRECKEL Daniel , FISCHER Joachim E. 
Published: November 2007

Acute mental stress may contribute to atherosclerosis by affecting inflammation and coagulation; however, the crosstalk between inflammation and coagulation during stress has not been studied. In the present study, we investigated the association of plasma fibrinogen, plasma IL-6 (interleukin-6) and free salivary cortisol with the procoagulant marker D-dimer reflecting fibrin formation both over a 2-h period and in response to acute mental stress. Twenty-one male volunteers (mean age, 47±8 years) underwent the Trier Social Stress Test combining a 3-min preparation phase, a 5-min job interview and 5-min mental arithmetic test before an audience. IL-6, fibrinogen, D-dimer and cortisol were measured immediately before and after stress, and after 45 min and 105 min of recovery from stress. Two distinct areas under the curve were computed to obtain integrated measures of total protein activity over the entire 2-h period and of stress reactivity of proteins. IL-6 (P&lt;0.001), fibrinogen (P=0.001), D-dimer (P=0.021) and cortisol (P&lt;0.001) had all significantly changed across the four time points assessed, as determined by ANOVA. For the entire 2-h period, total fibrinogen activity (R2=0.33, P=0.007) and total cortisol activity (ΔR2=0.17, P=0.034) explained 50% of the variance in total D-dimer activity. Stress-induced changes in fibrinogen (R2=0.47, P=0.001) and IL-6 (ΔR2=0.18, P=0.008) together explained 65% of the variance in D-dimer reactivity to stress. Total fibrin formation was independently predicted by fibrinogen and hypothalamo–pituitary–adrenal activity. Pro-inflammatory and procoagulant changes with stress were associated. Aside from fibrinogen reactivity, IL-6 reactivity was an independent predictor of stress-induced fibrin formation.
Increased levels of tumour necrosis factor-α (TNF-α) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction
Authors: Nyström Thomas , Nygren Arne , Sjöholm Åke 
Published: November 2007

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), SI (insulin sensitivity index; determined by isoglycaemic–hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-α (tumour necrosis factor-α), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and SI, and CRP, TNF-α, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P&lt;0.05), NTG (14.9 compared with 21.2%; P&lt;0.05) and SI [4.3 compared with 6.6 10−4 dl·kg−1 of body weight·min−1·(μ-units/ml)−1; P&lt;0.05], and adiponectin levels (3.1 compared with 6.4 μg/ml; P&lt;0.01) were all lower in patients with T2DM. TNF-α (6.9 compared with 1.8 pg/ml; P&lt;0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P&lt;0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-α concentrations and brachial artery diameter were negatively, whereas SI was positively, correlated with FMD. Adjustment for age weakened the association for SI, whereas TNF-α and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.
Use of the prone position in the acute respiratory distress syndrome: how should we assess benefit?
Authors: Treacher David F. 
Published: November 2007

Prone positioning of patients with acute respiratory failure was first suggested over 30 years ago. In the present issue of Clinical Science, Reutershan and co-workers have studied the changes in end-expiratory lung volume in 12 patients with ARDS (acute respiratory distress syndrome) over an 8 h period following manual turning from the supine to prone position. From the data presented, the authors suggest that baseline end-expiratory lung volume could be used to identify responders, and serial measurements would permit appropriate ‘dosing’ of the therapy. Although this is an interesting study that provides data that have rarely been collected when assessing the response to prone positioning, there are a number of limitations that need to be considered. However, despite the limitations, the study does stimulate a number of important questions related not only to the use of the prone position, but also to the management of patients with ARDS in general.
Impact of age on the vasovagal response provoked by sublingual nitroglycerine in routine tilt testing
Authors: Verheyden Bart , Gisolf Janneke , Beckers Frank , Karemaker John M. , Wesseling Karel H. , Aubert André E. , Wieling Wouter 
Published: November 2007

NTG (nitroglycerine) is used in routine tilt testing to elicit a vasovagal response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related vasovagal collapse patterns. The study groups consisted of 29 patients (16–71 years old, 17 females) with clinically suspected VVS (vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was inversely related to age (r=0.51, P=0.005). Accordingly, patients with a mean FAP fall &gt;1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30±10 years compared with 51±17 years; P=0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r=0.75, P&lt;0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a vasovagal episode depend on the magnitude of the underlying bradycardic response.
Structural risk minimization: a robust method for density‐dependence detection and model selection
Authors: Corani Giorgio , Gatto Marino 
Published: November 2007

Statistically distinguishing density‐dependent from density‐independent populations and selecting the best demographic model for a given population are problems of primary importance. Traditional approaches are PBLR (parametric bootstrapping of likelihood ratios) and Information criteria (IC), such as the Schwarz information criterion (SIC), the Akaike information criterion (AIC) or the Final prediction error (FPE). While PBLR is suitable for choosing from a couple of models, ICs select the best model from among a set of candidates. In this paper, we use the Structural risk minimization (SRM) approach. SRM is the model selection criterion developed within the Statistical learning theory (SLT), a theory of great generality for modelling and learning with finite samples. SRM is almost unknown in the ecological literature and has never been used to analyze time series.First, we compare SRM with PBLR in terms of their ability to discriminate between the Malthusian and the density‐dependent Ricker model. We rigorously repeat the experiments described in a previous study and find out that SRM is equally powerful in detecting density‐independence and much more powerful in detecting density‐dependence.Then, we compare SRM against ICs in terms of their ability to select one of several candidate models; we generate, via stochastic simulation, a huge amount of artificial time series both density‐independent and dependent, with and without exogenous covariates, using different dataset sizes, noise levels and parameter values. Our findings show that SRM outperforms traditional ICs, because generally a) it recognizes the model underlying the data with higher frequency, and b) it leads to lower errors in out‐of‐samples predictions. SRM superiority is specially apparent with short time series.We finally apply SRM to the population records of Alpine ibex Capra ibex living in the Gran Paradiso National Park (Italy), already investigated by other authors via traditional statistical methods; we both analyze their models and introduce some novel ones. We show that models that are best according to SRM show also the lowest leave‐one‐out cross‐validation error.
Distinguishing dung from blue, red and yellow‐backed duikers through noninvasive genetic techniques
Authors: Van Vliet Nathalie , Zundel Stéphanie , Miquel Christian , Taberlet Pierre , Nasi Robert 
Published: November 2007

AbstractDung counts have been widely used to estimate duiker abundance and densities in tropical African forests. However, one of the major limitations of this method is that species’ identification of dung based on morphological characteristics is extremely difficult in most cases. Some authors made the assumption that dung pellets could at least be distinguishable between the blue duiker, the red duikers and the yellow‐backed duiker. However, this study is the first attempt to test the reliability of field identification. In this study, we suggest a method based on a noninvasive genetic protocol to identify duiker species. The comparison of field and genetic identifications shows that only dung fromCephalophus silvicultorwas identified in the field without error. The rate of error for red duikers and the blue duiker is high and any attempt to distinguish among those species will result in wrong estimations for each species. We recommend the use of DNA tests to ensure reliable species’ identification when duiker censuses based on dung counts are used. This methodological input will probably strengthen the dung count technique and increase its reliability for duiker species abundance estimations and spatial distribution studies.
Remifentanil for general anaesthesia: a systematic review
Authors: Komatsu R. , Turan A. M. , Orhan‐Sungur M. , McGuire J. , Radke O. C. , Apfel C. C. 
Published: November 2007

SummaryWe performed a quantitative systematic review of randomised, controlled trials that compared remifentanil to short‐acting opioids (fentanyl, alfentanil, or sufentanil) for general anaesthesia. Eighty‐five trials were identified and these included a total of 13 057 patients. Intra‐operatively, remifentanil was associated with clinical signs of deeper analgesia and anaesthesia, such as fewer responses to noxious stimuli (relative risk 0.65, 95% CI 0.48–0.87), more frequent episodes of bradycardia (1.46, 1.04–2.05), more hypotension (1.68, 1.36–2.07) and less hypertension (0.60, 0.46–0.78). Postoperatively, remifentanil was associated with faster recovery (difference in extubation time of −2.03, 9.5% CI, −2.92 to −1.14 min), more frequent postoperative analgesic requirements (1.36, 1.21–1.53) and fewer respiratory events requiring naloxone (0.25, 0.14–0.47). Remifentanil had no overall impact on postoperative nausea (1.03, 0.97–1.09) or vomiting (1.06, 0.96–1.17), but was associated with twice as much shivering (2.15, 1.73–2.69). Remifentanil does not seem to offer any advantage for lengthy, major interventions, but may be useful for selected patients, e.g. when postoperative respiratory depression is a concern.
Pre‐operative analgesia with rectal diclofenac and/or paracetamol in children undergoing inguinal hernia repair
Authors: Riad W. , Moussa A. 
Published: November 2007

SummaryBoth rectal diclofenac and paracetamol are commonly used to treat acute postoperative pain in children but combining them to improve the quality of analgesia is controversial. This study aimed to detect whether the pre‐operative combined administration of rectal diclofenac and paracetamol is superior to either drug alone. One hundred and eight patients were randomly assigned to receive either rectal diclofenac 1 mg.kg−1 or paracetamol 40 mg.kg−1 or their combination 1 h prior to surgery. In the first 24 h postoperatively, pain was assessed using the Wong and Baker Pain Scale. If the patients experienced a pain score of 2 or more, morphine was given. The total dose of morphine and number of doses required were recorded. Children who received the rectal diclofenac‐paracetamol combination experienced a lower pain scale and a decreased need for morphine compared with children receiving each drug alone.