bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elite athletes’ duty to provide information on their whereabouts: Justifiable anti‐doping work or an indefensible surveillance regime?
Authors: Hanstad Dag Vidar , Loland Sigmund 
Published: January 2009

AbstractIn this article, we explain and reflect critically upon the athlete whereabouts reporting system in top‐level sports initiated by the World Anti‐Doping Agency (WADA). This system makes it compulsory for athletes who are in a registered testing pool in their national and/or international federation to submit information about their whereabouts. In this way, athletes are required to be available for a no advance notice doping test throughout the year. If an athlete provides incorrect information or cannot be found when a no advance notice test is supposed to be taken (a missed test), he or she may be given a warning. In most sports and national anti‐doping regulations, three such warnings within 18 months may be regarded as a violation of the doping regulations and may lead to exclusion from sport for between 3 months and 2 years. The system is controversial. In this article, we examine the key objections to the system and, more specifically, objections connected to ideas of justice and athletes’ autonomy and right to self‐determination. The argument will be a practical ethical one informed by a survey on attitudes towards the whereabouts system carried out among 236 athletes belonging to the registered testing pool in Norway. We conclude that if the basic principles of anti‐doping work are accepted, WADA's whereabouts reporting system represents nothing other than an efficient extension of this work.
The prognostic value of repeated measurement of N‐terminal pro‐B‐type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction
Authors: Kubánek Miloš , Goode Kevin M. , Lánská Věra , Clark Andrew L. , Cleland John G.F. 
Published: January 2009

AimsDecreased N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) during treatment of chronic heart failure (CHF) is associated with improved prognosis. However, there is lack of data from community‐based HF programmes. We hypothesized that plasma levels of NT‐proBNP, measured after optimization of pharmacotherapy in patients with CHF, may provide independent prognostic information when compared with baseline values and conventional prognostic markers.Methods and resultsN‐terminal pro‐B‐type natriuretic peptide was measured in 354 patients with CHF and left ventricular ejection fraction <45%, who had recently been enrolled in a community‐based HF programme. Patients underwent a 6 min walk test and clinical, echocardiographic and laboratory examinations. Pharmacotherapy was optimized; 318 patients survived until the second examination and measurement of NT‐proBNP, which was performed between the 4th and 6th month of follow‐up. During a median follow‐up of 38.8 months, 125 patients died. Follow‐up log NT‐proBNP was a better predictor of death than either baseline log NT‐proBNP or change in NT‐proBNP (χ2: 46.5 vs. 30.4 and 12.5, all P < 0.001). N‐terminal pro‐B‐type natriuretic peptide was consistently the strongest independent prognostic marker at predicting death or unplanned cardiovascular hospitalizations after baseline or follow‐up assessment.ConclusionThe measurement of NT‐proBNP after optimization of pharmacotherapy provides stronger prognostic information than either the baseline value, the change in NT‐proBNP, or other conventional methods of assessment.
ENGINEERING IMAGING: USING PARTICLE IMAGE VELOCIMETRY TO SEE PHYSIOLOGY IN A NEW LIGHT
Authors: Fouras Andreas , Dusting Jonathan , Sheridan John , Kawahashi Masaaki , Hirahara Hiroyuki , Hourigan Kerry 
Published: January 2009

SUMMARY

Despite the array of sophisticated imaging techniques available for biological applications, none of the standard biomedical techniques adequately provides the capability to measure motion and flow. Those techniques currently in use are particularly lacking in spatial and temporal resolution.
Herein, we introduce the technique of particle image velocimetry. This technique is a well‐established tool in engineering research and industry. Particle image velocimetry is continuing to develop and has an increasing number of variants.
Three case studies are presented: (i) the use of microparticle image velocimetry to study flow generated by high‐frequency oscillatory ventilation in a human airway model; (ii) the use of stereoparticle image velocimetry to study stirred cell and tissue culture devices; and (iii) a three‐dimensional X‐ray particle image velocimetry technique used to measure flow in an in vitro vascular flow model.
The case studies highlight the vast potential of applying the engineering technique of particle image velocimetry and its many variants to current research problems in physiology.
High‐pitched breath sounds indicate airflow limitation in asymptomatic asthmatic children
Authors: HABUKAWA Chizu , NAGASAKA Yukio , MURAKAMI Katsumi , TAKEMURA Tsukasa 
Published: January 2009

ABSTRACTBackground and objective:  Asthmatic children may have airway dysfunction even when asymptomatic, indicating that their long‐term treatment is less than optimal. Although airway dysfunction can be identified on lung function testing, performing these tests can be difficult in infants. We studied whether breath sounds reflect subtle airway dysfunction in asthmatic children.Methods:  The highest frequency of inspiratory breaths sounds (HFI) and the highest frequency of expiratory breath sounds (HFE) were measured in 131 asthmatic children while asymptomatic and with no wheezes for more than 2 weeks. No child was being treated with inhaled corticosteroids (ICS). Breath sounds were recorded and analysed by sound spectrography and compared with spirometric parameters. After initial evaluation, cases with more than step 2 (mild persistent) asthma were treated using inhaled fluticasone (100–200 µg/day) for 1 month, and then breath sound analysis and pulmonary function testing were repeated.Results:  On initial evaluation, HFI correlated with the percentage of predicted FEF50 (%FEF50), (r = −0.45, P < 0.001), the percentage of predicted FEF75 (%FEF75) (r = −0.456, P < 0.001), and FEV1 as a percentage of FVC (FEV1/FVC (%)) (r = −0.32, P < 0.001). HFI did not correlate with the percentage of predicted PEF (%PEF). The 69 children with lower than normal %FEF50 were then treated with ICS. The %FEF50 and %FEF75 improved after ICS treatment, and increases in %FEF50 (P < 0.005) correlated with decreases in HFI (P < 0.001).Conclusions:  Higher HFI in asymptomatic asthmatic children may indicate small airway obstruction. Additional ICS treatment may improve the pulmonary function indices representing small airway function with simultaneous HFI decreases in such patients.
TGF‐β effects on airway smooth muscle cell proliferation, VEGF release and signal transduction pathways
Authors: SHIN Joo Hwa , SHIM Jae Won , KIM Deok Soo , SHIM Jung Yeon 
Published: January 2009

ABSTRACTBackground and objective:  Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal‐regulated kinase (ERK), p38MAPK and c‐Jun NH2‐terminal kinase (JNK). The effect of transforming growth factor (TGF)‐β on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated.Methods:  ASM cells were growth‐arrested for 48 h then stimulated with platelet‐derived growth factor (PDGF), TGF‐β and dexamethasone. ASM cells were also treated with specific inhibitors of MAPK (PD98059), PI3K (wortmannin) and JNK (SP600125). Cell proliferation and VEGF concentrations were measured.Results:  TGF‐β neither augmented ASM cell proliferation nor showed a synergistic effect on PDGF‐mediated ASM cell proliferation. Dexamethasone did not suppress ASM cell proliferation. VEGF release was augmented by TGF‐β stimulation in a time‐dependent manner, and was further enhanced by co‐stimulation with PDGF and TGF‐β. Dexamethasone suppressed VEGF release significantly. TGF‐β enhanced PI3K phosphorylation, while PDGF augmented both ERK and PI3K phosphorylation. Wortmannin inhibited both TGF‐β‐ and PDGF‐stimulated VEGF release.Conclusions:  TGF‐β may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation.
In vitro cytotoxicity of CD8+ T cells in multi‐drug‐resistant tuberculosis. A preliminary report
Authors: SADA‐OVALLE Isabel , TORRE‐BOUSCOULET Luis , VALDEZ‐VÁZQUEZ Rafael , LASCURAIN Ricardo 
Published: January 2009

ABSTRACTBackground and objective:  Specific CD8+ T‐cell cytotoxicity has been recognized as being involved in the elimination of drug‐susceptible tuberculosis (DS‐TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi‐drug‐resistant tuberculosis (MDR‐TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR‐TB patients and compare it with that of DS‐TB patients, as well as purified protein derivative (PPD)+ and PPD− subjects.Methods:  Cytotoxic activity of CD8+ T cells from MDR‐TB patients, DS‐TB patients, PPD+ and PPD− subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus.Results:  Twenty‐eight subjects were studied (7 MDR‐TB patients, 7 DS‐TB patients, 7 PPD+ subjects and 7 PPD− subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR‐TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS‐TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD− subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR‐TB patients than PPD+ and PPD− subjects (P = 0.003), but not compared with that for DS‐TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR‐TB patients.Conclusions:  CD8+ T cells from MDR‐TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR‐TB.
En bloc paediatric kidney transplant: is this the best use of a scarce resource?
Authors: Lam Vincent W. T. , Laurence Jerome M. , Robertson Paul , Hawthorne Wayne , Ryan Brendan J. , Lau Howard M. H. , Allen Richard D. M. , Pleass Henry C. C. 
Published: January 2009

AbstractBackground:  Kidney transplants using organs from paediatric cadaver donors are uncommon and technically difficult. It has become accepted practice to transplant both kidneys en bloc from donors of 5 years into a single recipient. We aim to compare outcomes of en bloc kidney (EBK) transplants versus single kidney (SK) transplants from cadaver donors of age 5 years and lesser.Methods:  Data reported to Australia and New Zealand Dialysis and Transplant Registry from 1989 to 2004 were analysed.Results:  From donors 5 years of age and younger, there were 33 EBK and 38 SK transplants carried out. Overall graft survival rates at 1 and 5 years were 78 and 61%, respectively, in the EBK group and 63 and 55%, respectively, in the SK group (P = 0.94). Vascular thrombosis was the most common cause of early graft loss with an incidence of 11 and 18%, respectively, in the EBK and SK groups (P = 0.5).Conclusion:  There is a trend towards a lower vascular thrombosis rate and a better long‐term graft survival in EBK transplants. These transplants will remain a technical challenge for the surgeon and EBK transplants should remain the technique of choice for donors of 5 years and lesser.
Aortic fat pad and atrial fibrillation: cardiac lymphatics revisited
Authors: Lupinski Ryszard W. 
Published: January 2009

AbstractThe lymphatics of the heart have not generated any broad or sustained interest among clinicians. Few publications on cardiac lymphatics are available, the anatomy is not routinely known and the true role of cardiac lymphatics remains doubtful. One important anatomical concept needing clarification is that of the lymphatic drainage of conduction tissue. The sinoatrial node lymphatic collector and right principal lymphatic trunk are both incorporated into the aortic fat pad of the ascending aorta and are the most frequently damaged lymphatic vessels during cardiac surgery. Thus, preservation of the aortic fat pad and its lymphatic collectors should reduce the incidence of new atrial fibrillation observed in patients after cardiac surgery. This review assesses current knowledge of cardiac lymphatics and shows their possible role in triggering arrhythmias in the postoperative period.
Regional cortical blood flow changes following sodium lactate infusion in Alzheimer's disease
Authors: Kálmán János , Palotás András , Kis Gabriella , Boda Krisztina , Túri Piroska , Bari Ferenc , Domoki Ferenc , Dóda Ildikó , Árgyelán Miklós , Vincze Gábor , Séra Teréz , Csernay László , Janka Zoltán , Pávics László 
Published: January 2009

AbstractBilateral temporoparietal hypoperfusion is a characteristic single photon emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate is a metabolic vasodilator and is known to provoke increased cerebral blood flow (CBF) in healthy adults. This work investigated whether lactate, which is present in high concentrations in AD cerebrospinal fluid, affects AD‐specific perfusion abnormalities. Twenty mild‐to‐moderately demented AD probands participated in the self‐controlled study. The regional CBF was examined utilizing 99mTc‐HMPAO SPECT after sodium lactate infusion (0.5 m, 5 mL/kg body weight) and 0.9% NaCl infusion, one on each of two separate days. Despite the vasodilatator effects of sodium lactate, AD rCBF patterns did not show increase in temporo‐parietal regions after its infusion. AD‐specific bi‐temporo‐parietal reduction in CBF was accompanied by further hypoperfusion in the parieto‐occipital areas after the sodium lactate infusion in seven patients, while no CBF changes were observed in the case of the remaining 13 probands. The pattern of the CBF abnormalities was not correlated with the apolipoprotein E genotype. The decreased vascular responsiveness to sodium lactate reflects disturbed vasoregulatory processes in AD and it is unlikely that lactate would have any relevance in the treatment of AD‐related cerebral hypoperfusion, but could be used to improve the value of perfusion SPECT in the diagnosis of AD.
Retinoic acid synthesis by a population of NG2‐positive cells in the injured spinal cord
Authors: Mey Jörg , J. Morassutti Dante , Brook Gary , Liu Rong‐Huan , Zhang Yi‐Ping , Koopmans Guido , McCaffery Peter 
Published: January 2009

AbstractRetinoic acid (RA) promotes growth and differentiation in many developing tissues but less is known about its influence on CNS regeneration. We investigated the possible involvement of RA in rat spinal cord injury (SCI) using the New York University (NYU) impactor to induce mild or moderate spinal cord contusion injury. Changes in RA at the lesion site were determined by measuring the activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at days 8–14 following the injuries. RALDH2 was the only detectable RALDH present in the control or injured spinal cord. The cellular localization of RALDH2 was identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected in oligodendroglia positive for the markers RIP and CNPase. Expression was also intense in the arachnoid membrane surrounding the spinal cord. After SCI the increase in RALDH2 was independent of the RIP‐ and CNPase‐positive cells, which were severely depleted. Instead, RALDH2 was present in a cell type not previously identified as capable of synthesizing RA, that expressed NG2 and that was negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann cells and immature lymphocytes. We postulate that the RALDH2‐ and NG2‐positive cells migrate into the injured sites from the adjacent arachnoid membrane, where the RALDH2‐positive cells proliferate substantially following SCI. These findings indicate that close correlations exist between RA synthesis and SCI and that RA may play a role in the secondary events that follow acute SCI.
Estrogen enhances light‐induced activation of dorsal raphe serotonergic neurons
Authors: Abizaid Alfonso , Mezei Gabor , Thanarajasingam Gita , Horvath Tamas L. 
Published: January 2009

AbstractThe serotonergic system has been implicated in the modulation of physiological processes including circadian rhythms, learning, memory, mood and food intake. In females, cessation of ovarian function produces deleterious changes in all of these processes and estrogen treatment often ameliorates these conditions. Estrogen may produce these effects by acting on the midbrain raphe, an estrogen‐sensitive region that receives direct projections from sensory systems. Here we examined the ability of estradiol to modulate neuronal responses of neurons within raphe nuclei to photic stimulation. Ovariectomized rats treated with estradiol or cholesterol were killed 1 h after the normal onset of light (Zeitgeber time 0) or after a 2‐h phase advance (Zeitgeber time 22). In a second study, estradiol‐treated ovariectomized rats under constant dark conditions were exposed to light 2 h before the subjective onset of circadian time [(CT)22] and killed 1 h later (CT23). The brains from all animals were processed for Fos and/or serotonin (5‐HT) immunocytochemistry. Comparisons showed that the phase shift increased Fos immunoreactivity in all dorsal raphe nucleus (DRN) regions. Although estradiol did not alter the overall number of Fos‐positive nuclei, it significantly increased the number of Fos/5‐HT double‐labelled cells in the medial and lateral DRN. In contrast, neither a phase shift nor estradiol altered the number of Fos‐immunoreactive cells or the proportion of Fos‐positive 5‐HT cells in the median raphe nucleus. Results reveal that the DRN 5‐HT system responds to changes in the light : dark cycle and that these responses are modulated by estrogen.
Ratio and time requirements on operant schedules: effort‐related effects of nucleus accumbens dopamine depletions
Authors: Mingote Susana , Weber Suzanne M. , Ishiwari Keita , Correa Mercè , Salamone John D. 
Published: January 2009

AbstractAccumbens dopamine (DA) depletions produce deficits that are related to the ratio requirement of the operant schedule; however, it is also possible that time without reinforcement is a factor. The present study examined the effects of accumbens DA depletions in rats using variable interval (VI) schedules with additional fixed ratio (FR) requirements. Four VI schedules were used (VI 60/FR 1, VI 120/FR 1, VI 60/FR 10, VI 120/FR 10). Attachment of the additional work requirement increased response rates under control conditions. After surgery, there was no interaction between interval level (i.e. 60 vs. 120 s) and DA depletion, but there was a significant interaction between ratio requirement (i.e. 1 vs. 10) and DA depletion within the first week after surgery. DA depletions substantially impaired performance on the schedules with added FR 10 requirements, an effect that was largely dependent upon a reduction in fast responses (i.e. interresponse times less than 1.0 s). There was little effect of DA depletion on overall responding on VI 60/FR 1 and VI 120/FR 1 schedules. DA depletions also increased the tendency to take long pauses in responding (i.e. > 20.0 s), and this effect was evident across all schedules tested. Thus, accumbens DA depletions interact with work requirements and blunt the rate‐enhancing effects of moderate size ratios, and also enhance the tendency to pause. Attachment of ratio requirements to interval schedules is a work‐related response cost that provides a challenge to the organism, and DA in nucleus accumbens appears to be necessary for adapting to this challenge.
IGF‐I neuroprotection in the immature brain after hypoxia‐ischemia, involvement of Akt and GSK3β?
Authors: Brywe Katarina G. , Mallard Carina , Gustavsson Malin , Hedtjärn Maj , Leverin Anna‐Lena , Wang Xiaoyang , Blomgren Klas , Isgaard Jörgen , Hagberg Henrik 
Published: January 2009

AbstractInsulin‐like growth factor I (IGF‐I) is a neurotrophic factor that promotes neuronal growth, differentiation and survival. Neuroprotective effects of IGF‐I have previously been shown in adult and juvenile rat models of brain injury. We wanted to investigate the neuroprotective effect of IGF‐I after hypoxia‐ischemia (HI) in 7‐day‐old neonatal rats and the mechanisms of IGF‐I actions in vivo. We also wanted to study effects of HI and/or IGF‐I on the serine/threonine kinases Akt and glycogen synthase kinase 3β (GSK3β) in the phophatidylinositol‐3 kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and phosphorylated GSK3β (pGSK3β) immunoreactivity was lost in the ipsilateral and reduced in the contralateral hemisphere. After 45 min, pAkt levels were restored to control values, whereas pGSK3β remained low 4 h after HI. Administration of IGF‐I (50 µg i.c.v.) after HI resulted in a 40% reduction in brain damage (loss of microtubule‐associated protein) compared with vehicle‐treated animals. IGF‐I treatment without HI was shown to increase pAkt whereas pGSK3β decreased in the cytosol, but increased in the nuclear fraction. IGF‐I treatment after HI increased pAkt in the cytosol and pGSK3β in both the cytosol and the nuclear fraction in the ipsilateral hemisphere compared with vehicle‐treated rats, concomitant with a reduced caspase‐3‐ and caspase‐9‐like activity. In conclusion, IGF‐I induces activation of Akt during recovery after HI which, in combination with inactivation of GSK3β, may explain the attenuated activation of caspases and reduction of injury in the immature brain.
Presynaptic ‘Cav2.3‐containing’ E‐type Ca2+ channels share dual roles during neurotransmitter release
Authors: Kamp M. A. , Krieger A. , Henry M. , Hescheler J. , Weiergräber M. , Schneider T. 
Published: January 2009

AbstractCa2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis. Within the group of ten cloned voltage‐gated Ca2+ channels, the Cav2.3‐containing E‐type Ca2+ channels are involved in various physiological processes, such as neurotransmitter release and exocytosis together with other voltage‐gated Ca2+ channels of the Cav1, Cav2 and Cav3 subfamily. However, E‐type Ca2+ channels also exhibit several subunit‐specific features, most of which still remain poorly understood. Cav2.3‐containing R‐type channels (here called ‘E‐type channels’) are also located in presynaptic terminals and interact with some synaptic vesicle proteins, the so‐called SNARE proteins, although lacking the classical synprint interaction site. E‐type channels trigger exocytosis and are also involved in long‐term potentiation. Recently, it was shown that the interaction of Cav2.3 with the EF‐hand motif containing protein EFHC1 is involved in the aetiology and pathogenesis of juvenile myoclonic epilepsy.