bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quantitative Comparison of Four Current Portable Ultrasound Bladder Scanners
Authors: Small D.R. , Watson A. , McConnachie A. 
Published: September 2008

Objective: Portable bladder ultrasound is a necessary investigation in urology and other disciplines. Scanners image with or without bladder wall detection—others provide only numeric readout. In volunteers, we compared measurements from four current scanners. Methods: Bardscan, Verathon BVI3000, Verathon BVI6100 and Sonosite iLook15 were used with 28 healthy volunteers, with scanners in random order. Ordinary least squares regression modelled the measured volumes of each volunteer using each scanner. For each patient—scanner combination, the predicted volume from this model (corrected for the average bias of each scanner) represents the best estimate of the volume, and the difference between the measured bladder volume and the predicted volume was an estimate of the error of that measurement. Results: The iLook15 and Bardscan underpredict, and the BVI3000 and BVI6100 overpredict, relative to the average of the four scanners ( p< 0.05). The BVI3000 had slightly greater error variability than the others ( p = 0.051). Measurement error appears more variable for larger volumes. Conclusion: The two real-time imaging systems (the SonoSite iLook15 and the Bard-scan) tended to give lower volume estimates than the two systems from the same manufacturer (the BVI3000 and BVI6100). Of the two BVI scanners, the 6100 had markedly less variable error.
On contemporaneous controls, unlikely outcomes, boxes and replacing the ‘Student’: Good statistical practice in pharmacology, problem 3
Authors: Lew M J 
Published: September 2008

This paper is intended to assist pharmacologists to make the most of statistical analysis and avoid common errors. A scenario, in which an experimenter performed an experiment in two separate stages, combined the control groups for analysis and found some surprising results, is presented. The consequences of combined controls are discussed, appropriate display and analysis of the data are described, and an analysis of the likelihood of erroneous conclusions is made. Comparisons between data from separately conducted experimental series are hazardous when there is any possibility that the properties of the experimental units have changed between the series. Experiments that have been performed independently should be analyzed independently. Unlikely or surprising results should be treated with caution and a high standard of evidence should be required, and verification by repeated experiments should be performed and reported. Box and whisker plots contain more information than plots more commonly used to display for qualitative variables and should be used where the sample size is large enough (say, n5). In most biomedical experiments the observations are not random samples from large populations as assumed by conventional parametric analyses such as Student's t‐test, and so permutation tests, which do not lose their validity when a sampled population is non‐normal or when the data are not random samples, should frequently be used instead of Student's t‐tests.British Journal of Pharmacology (2008) 155, 797–803; doi:10.1038/bjp.2008.350; published online 22 September 2008
The pharmacological challenge to tame the transient receptor potential vanilloid‐1 (TRPV1) nocisensor
Authors: Holzer P 
Published: September 2008

The transient receptor potential vanilloid‐1 (TRPV1) cation channel is a receptor that is activated by heat (>42 °C), acidosis (pH<6) and a variety of chemicals among which capsaicin is the best known. With these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurones, although some non‐neuronal cells and neurones in the brain also express TRPV1. The activity of TRPV1 is controlled by a multitude of regulatory mechanisms that either cause sensitization or desensitization of the channel. As many proalgesic pathways converge on TRPV1 and this nocisensor is upregulated and sensitized by inflammation and injury, TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for the pharmacological control of pain. As a consequence, TRPV1 agonists causing defunctionalization of sensory neurones and a large number of TRPV1 blockers have been developed, some of which are in clinical trials. A major drawback of many TRPV1 antagonists is their potential to cause hyperthermia, and their long‐term use may carry further risks because TRPV1 has important physiological functions in the peripheral and central nervous system. The challenge, therefore, is to pharmacologically differentiate between the physiological and pathological implications of TRPV1. There are several possibilities to focus therapy specifically on those TRPV1 channels that contribute to disease processes. These approaches include (i) site‐specific TRPV1 antagonists, (ii) modality‐specific TRPV1 antagonists, (iii) uncompetitive TRPV1 (open channel) blockers, (iv) drugs interfering with TRPV1 sensitization, (v) drugs interfering with intracellular trafficking of TRPV1 and (vi) TRPV1 agonists for local administration.British Journal of Pharmacology(2008)155, 1145–1162; doi:fn2; published online 22 September 2008
Low doses of α2‐adrenoceptor antagonists augment spinal morphine analgesia and inhibit development of acute and chronic tolerance
Authors: Milne B , Sutak M , Cahill C M , Jhamandas K 
Published: September 2008

Background and purpose:Ultra‐low doses of opioid receptor antagonists augment spinal morphine antinociception and block the induction of tolerance. Considering the evidence demonstrating functional and physical interactions between the opioid and α2‐adrenoceptors, this study investigated whether ultra‐low doses of α2‐adrenoceptor antagonists also influence spinal morphine analgesia and tolerance.Experimental approach:Effects of low doses of the competitive α2‐adrenoceptor antagonists—atipamezole (0.08, 0.8 ng), yohimbine (0.02, 2 ng), mirtazapine (0.02 ng) and idazoxan (0.08 ng) were investigated on intrathecal morphine analgesia, as well as acute and chronic morphine antinociceptive tolerance using the rat tail flick and paw pressure tests.Key results:At doses markedly lower than those producing α2‐adrenoceptor blockade, atipamezole, yohimbine, mirtazapine and idazoxan, prolonged the antinociceptive effects of morphine. When co‐administered with repeated acute spinal injections of morphine, all four agents blocked the induction of acute tolerance. Co‐injection of atipamezole with morphine for 5 days inhibited the development of tolerance in a chronic treatment paradigm. Spinal administration of atipamezole also reversed established antinociceptive tolerance to morphine as indicated by the restoration of morphine antinociceptive potency. The effects of atipamezole on spinal morphine tolerance were not influenced by treatment with 6‐hydroxydopamine.Conclusions and implications:Low doses of competitive α2‐adrenoceptor antagonists can augment acute morphine analgesia and block or reverse tolerance to spinal administration of morphine. These actions are interpreted in terms of their interaction with an opioid‐α2‐adrenoceptor complex, whose activity may have a function in the genesis of analgesic tolerance.British Journal of Pharmacology(2008)155, 1264–1278; doi:10.1038/bjp.2008.353; published online 22 September 2008
Luteolin inhibits myelin basic protein‐induced human mast cell activation and mast cell‐dependent stimulation of Jurkat T cells
Authors: Kempuraj D , Tagen M , Iliopoulou B P , Clemons A , Vasiadi M , Boucher W , House M , Wolfberg A , Theoharides T C 
Published: September 2008

Background and purpose:Allergic inflammation and autoimmune diseases, such as atopic dermatitis, psoriasis and multiple sclerosis (MS), involve both mast cell and T‐cell activation. However, possible interactions between the two and the mechanism of such activations are largely unknown.Experimental approach:Human umbilical cord blood‐derived cultured mast cells (hCBMCs) and Jurkat T cells were incubated separately or together, following activation with myelin basic protein (MBP), as well as with or without pretreatment with the flavonoid luteolin for 15 min. The supernatant fluid was assayed for inflammatory mediators released from mast cells and interleukin (IL)‐2 release from Jurkat cells.Key results:MBP (10 μM) stimulates hCBMCs to release IL‐6, IL‐8, transforming growth factor (TGF)‐β1, tumour necrosis factor‐α (TNF‐α), vascular endothelial growth factor (VEGF), histamine and tryptase (n=6,P<0.05). Addition of mast cells to Jurkat cells activated by anti‐CD3/anti‐CD28 increases IL‐2 release by 30‐fold (n=3,P<0.05). MBP‐stimulated mast cells and their supernatant fluid further increase Jurkat cell IL‐2 release (n=3,P<0.05). Separation of mast cells and activated Jurkat cells by a Transwell permeable membrane inhibits Jurkat cell stimulation by 60%. Pretreatment of Jurkat cells with a TNF‐neutralizing antibody reduces IL‐2 release by another 40%. Luteolin pretreatment inhibits mast cell activation (n=3–6,P<0.05), Jurkat cell activation and mast cell‐dependent Jurkat cell stimulation (n=3,P<0.05).Conclusions and implications:Mast cells can stimulate activated Jurkat cells. This interaction is inhibited by luteolin, suggesting that this flavonoid may be useful in the treatment of autoimmune diseases.British Journal of Pharmacology(2008)155, 1076–1084; doi:10.1038/bjp.2008.356; published online 22 September 2008
Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine
Authors: De Man J G , De Winter B Y , De Schepper H U , Herman A G , Pelckmans P A 
Published: September 2008

Background and purpose:Tachykinin NK3 receptors are widely expressed in the mouse gastrointestinal tract but their functional role in enteric neuromuscular transmission remains unstudied in this species. We investigated the involvement of NK3 receptors in cholinergic neurotransmission in the mouse stomach and small intestine.Experimental approach:Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings. Effects of NK3 agonists and antagonists were studied on contractions to EFS of enteric nerves and to carbachol.Key results:EFS induced frequency‐dependent tetrodotoxin‐sensitive contractions, which were abolished by atropine. The cholinergic contractions to EFS in the stomach were enhanced by the NK3 antagonist SR142801, but not affected by the NK3 agonist senktide or neurokinin B. The cholinergic contractions to EFS in the small intestine were not affected by SR142801, but dose‐dependently inhibited by senktide and neurokinin B. This inhibitory effect was prevented by SR142801 but not by hexamethonium. SR142801, senktide or neurokinin B did not induce any response per se in the stomach and small intestine and did not affect contractions to carbachol.Conclusions and implications:NK3 receptors modulate cholinergic neurotransmission differently in the mouse stomach and small intestine. Blockade of NK3 receptors enhanced cholinergic transmission in the stomach but not in the intestine. Activation of NK3 receptors inhibited cholinergic transmission in the small intestine but not in the stomach. This indicates a physiological role for NK3 receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility.British Journal of Pharmacology (2008) 155, 1195–1203; doi:10.1038/bjp.2008.357; published online 22 September 2008
Intra‐ and extrarenal arteries exhibit different profiles of contractile responses in high glucose conditions
Authors: Nobe K , Nezu Y , Tsumita N , Hashimoto T , Honda K 
Published: September 2008

Background and purpose:The renal artery (RA) has been extensively investigated for the assessment of renal vascular function/dysfunction; however, few studies have focused on the intrarenal vasculature.Experimental approach:We devised a microvascular force measurement system, which allowed us to measure contractions of interlobar arteries (ILA), isolated from within the mouse kidney and prepared without endothelium.Key results:KCl (50 mM) induced similar force development in the aorta and RA but responses in the ILA were about 50% lower. Treatment of RA with 10 μMphenylephrine (PE), 10 nMU46619 (thromboxane A2analogue) or 10 μMprostaglandin F2αelicited a response greater than 150% of that induced by KCl. In ILA, 10 nMU46619 elicited a response that was 130% of the KCl‐induced response; however, other agonists induced levels similar to that induced by KCl. High glucose conditions (22.2 mMglucose) significantly enhanced responses in RA and ILA to PE or U46619 stimulation. This enhancement was suppressed by rottlerin, a calcium‐independent PKC inhibitor, indicating that glucose‐dependent, enhanced small vessel contractility in the kidney was linked to the activation of calcium‐independent PKC.Conclusion and implications:Extra‐ and intrarenal arteries exhibit different profiles of agonist‐induced contractions. In ILA, only U46619 enhanced small vessel contractility in the kidney, which might lead to renal dysfunction and nephropathy through reduced intrarenal blood flow rate. A model has been established, which will allow the assessment of contractile responses of intrarenal arteries from murine models of renal disease, including type 2 diabetes.British Journal of Pharmacology(2008)155, 1204–1213; doi:10.1038/bjp.2008.365; published online 22 September 2008
Mono‐galloyl glucose derivatives are potent poly(ADP‐ribose) glycohydrolase (PARG) inhibitors and partially reduce PARP‐1‐dependent cell death
Authors: Formentini L , Arapistas P , Pittelli M , Jacomelli M , Pitozzi V , Menichetti S , Romani A , Giovannelli L , Moroni F , Chiarugi A 
Published: September 2008

Background and purpose:Maintenance of poly(ADP‐ribose) (PAR) polymers at homoeostatic levels by PAR glycohydrolase (PARG) is central in cell functioning and survival. Yet the pharmacological relevance of PARG inhibitors is still debated. Gallotannin, a complex mixture of hydrolysable tannins from oak gall, inhibits PARG but which of its constituents is responsible for the inhibition and whether the pharmacodynamic properties are due to its antioxidant properties, has not yet been established.Experimental approach:A structure–activity relationship study was conducted on different natural and synthetic tannins/galloyl derivatives as potential PARG inhibitors, using a novel in vitro enzymic assay. Cytotoxicity was assayed in cultured HeLa cells.Key results:Mono‐galloyl glucose compounds were potent inhibitors of PARG, with activities similar to that of ADP‐(hydroxymethyl) pyrrolidinediol, the most potent PARG inhibitor yet identified. When tested on HeLa cells exposed to the PAR polymerase (PARP)‐1‐activating compound 1‐methyl‐3‐nitro‐1‐nitrosoguanidine (MNNG), 3‐galloyl glucose weakly inhibited PAR degradation. Conversely, the more lipophilic, 3‐galloyl‐1,2‐O‐isopropylidene glucose, despite being inactive on the pure enzyme, efficiently prolonged the half‐life of the polymers in intact HeLa cells. Also, PARG inhibitors, but not radical scavengers, reduced, in part, cell death caused by MNNG.Conclusions and implications:Taken together, our findings identify mono‐galloyl glucose derivatives as potent PARG inhibitors, and emphasize the active function of this enzyme in cell death.British Journal of Pharmacology (2008) 155, 1235–1249; doi:10.1038/bjp.2008.370; published online 22 September 2008
Peroxynitrite: in vivo cardioprotectant or arrhythmogen?
Authors: Eaton P , Clements‐Jewery H 
Published: September 2008

The factors that determine susceptibility to lethal ventricular arrhythmias during myocardial ischaemia and reperfusion in vivo are complex, but the balance between proarrhythmic and antiarrhythmic endogenous substances is likely to be important. However, in this context, it is not well established what effect endogenously produced peroxynitrite has on arrhythmias that develop during ischaemia/reperfusion in vivo. The study by Kiss et al., published in this issue of the BJP, provides some insights to this problem. We discuss the wider implications of this study as well as issues that still require resolution.British Journal of Pharmacology (2008) 155, 972–973; doi:fn1; published online 22 September 2008
Protective action of doxycycline against diabetic cardiomyopathy in rats
Authors: Yaras N , Sariahmetoglu M , Bilginoglu A , Aydemir‐Koksoy A , Onay‐Besikci A , Turan B , Schulz R 
Published: September 2008

Background and purpose:Reactive oxygen and nitrogen species play an important role in the development of diabetic cardiomyopathy. They can activate matrix metalloproteinases (MMPs), and MMP‐2 in particular is known to mediate early consequences of oxidative stress injury in the heart. Therefore, we investigated the role of MMP‐2 and the effect of the MMP inhibitor doxycycline on the changes of heart function caused by diabetes.Experimental approach:Using streptozotocin‐induced diabetic rats, we evaluated the effect of doxycycline on both mechanical and electrical function of isolated hearts, papillary muscle and cardiomyocytes.Key results:Doxycycline abolished the diabetes‐induced depression in left ventricular developed pressure and the rates of changes in developed pressure in isolated hearts and normalized the prolongation of the action potential in papillary muscles. In cardiomyocytes isolated from doxycycline‐treated diabetic rats, the altered kinetic parameters of Ca2+ transients, depressed Ca2+ loading of sarcoplasmic reticulum and basal intracellular Ca2+ level, and the spatio‐temporal properties of Ca2+ sparks were significantly restored. Gelatin zymography and western blot data indicated that the diabetes‐induced alterations in MMP‐2 activity and protein level, level of tissue inhibitor of matrix metalloproteinase‐4 and loss of troponin I were restored to control levels with doxycycline.Conclusions and implications:Our data suggest that these beneficial effects of doxycycline on the mechanical, electrical and biochemical properties of the diabetic rat heart appear, at least in part, to be related to inhibition of MMP activity, implying a role for MMPs in the development of diabetic cardiomyopathy.British Journal of Pharmacology (2008) 155, 1174–1184; doi:10.1038/bjp.2008.373; published online 22 September 2008
Matched Case-Control Analysis of Polymicrobial Bloodstream Infection In A Neonatal Intensive Care Unit
Authors: Bizzarro Matthew J. , Dembry Louise-Marie , Baltimore Robert S. , Gallagher Patrick G. 
Published: September 2008

Objective.To compare and contrast the epidemiology of polymicrobial and monomicrobial bloodstream infections (BSIs) in newborn intensive care unit (NICU) patients.Design.Retrospective, matched case-control study.Setting.The Yale-New Haven Hospital NICU from 1989 through 2006.Subjects.NICU patients with BSIs.Methods.Each neonate with polymicrobial BSI (case patient) was matched to one neonate with monomicrobial BSI (control patient), by birth date, weight, and sex; and univariate and multivariate analyses were performed.Results.One hundred five cases of polymicrobial BSI were identified in 102 infants, representing 10% of all neonatal BSIs in our institution. Coagulase-negative staphylococci were the most common organisms recovered from culture. Infants with polymicrobial BSI had later onset of infection than infants with monomicrobial BSI (mean day of life, 37.5 vs 24.0;P< .001). Polymicrobial BSI occurred more frequently among infants with a severe underlying condition than in those without such a condition (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.2) and among infants requiring an indwelling central venous catheter for a prolonged duration (mean, 16.9 days, compared with 9.8 days for infants with monomicrobial BSI;P= .001). Multivariate analysis revealed that later onset of infection (adjusted OR [aOR], 1.02; 95% CI, 1.00-1.04) and presence of a severe underlying condition (aOR, 1.91; 95% CI, 1.12-3.38) were independent risk factors for polymicrobial BSI. No differences in outcome or mortality were observed.Conclusions.Changes in the microbiology and epidemiology of NICU-related polymicrobial BSI have occurred since the last North American review. In the present study, although differences were observed, most risk factors and outcomes were similar between monomicrobial BSI and polymicrobial BSI. Epidemiologic surveillance is critical to identify trends associated with neonatal polymicrobial BSI, particularly those that may impact preventative strategies, diagnostic measures, and therapeutic interventions.
Can sugars be produced from fatty acids? A test case for pathway analysis tools
Authors: de Figueiredo Luis F. , Schuster Stefan , Kaleta Christoph , Fell David A. 
Published: September 2008

Abstract
Motivation: In recent years, several methods have been proposed for determining metabolic pathways in an automated way based on network topology. The aim of this work is to analyse these methods by tackling a concrete example relevant in biochemistry. It concerns the question whether even-chain fatty acids, being the most important constituents of lipids, can be converted into sugars at steady state. It was proved five decades ago that this conversion using the Krebs cycle is impossible unless the enzymes of the glyoxylate shunt (or alternative bypasses) are present in the system. Using this example, we can compare the various methods in pathway analysis.
Results: Elementary modes analysis (EMA) of a set of enzymes corresponding to the Krebs cycle, glycolysis and gluconeogenesis supports the scientific evidence showing that there is no pathway capable of converting acetyl-CoA to glucose at steady state. This conversion is possible after the addition of isocitrate lyase and malate synthase (forming the glyoxylate shunt) to the system. Dealing with the same example, we compare EMA with two tools based on graph theory available online, PathFinding and Pathway Hunter Tool. These automated network generating tools do not succeed in predicting the conversions known from experiment. They sometimes generate unbalanced paths and reveal problems identifying side metabolites that are not responsible for the carbon net flux. This shows that, for metabolic pathway analysis, it is important to consider the topology (including bimolecular reactions) and stoichiometry of metabolic systems, as is done in EMA.
Contact: ldpf@minet.uni-jena.de; schuster@minet.uni-jena.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Postharvest Fruit Rots in Apples Caused by Botrytis cinerea, Phacidiopycnis washingtonensis, and Sphaeropsis pyriputrescens
Authors: Xiao C. L. , Kim Y. K. 
Published: September 2008

Postharvest fruit rot diseases can be a limiting factor for storage of apples, and identifying target pathogens is the first necessary step for development and implementation of relevant measures for disease control. However, the symptoms of two new diseases, Sphaeropsis rot and speck rot, are similar to those of gray mold, and the two newly recognized diseases are often misdiagnosed as gray mold. The objective of this article is to provide a practical guide to diagnosis of these three diseases in apples. Accepted for publication 14 July 2008. Published 19 September 2008.