bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective quality of life of Nigerian schizophrenia patients: sociodemographic and clinical correlates
Authors: Adewuya A. O. , Makanjuola R. O. A.
Published: April 2009

Objective:  Subjective quality of life (QOL) is dependent upon culture and its evaluation based on one’s particular belief system. This study aimed to examine the subjective QOL of Nigerian out‐patients with schizophrenia and its correlates.

Method:  Out‐patients with Schizophrenia (n = 99) completed the WHOQOL‐BREF as a measure of their subjective QOL. Sociodemographic, illness related and medication related details were also obtained.

Results:  Overall, 21 patients (21.2%) were categorised as having ‘good’ and 36 (36.4%) as having ‘poor’ subjective QOL. ‘Poor’ subjective QOL correlated with anxiety/depression symptoms (OR 4.88, 95% CI 2.93–11.48), comorbid medical problems (OR 4.75, 95% CI 1.43–16.33), unemployment (OR 3.75, 95% CI 1.25–11.72) and poor social support (OR 4.60, 95% CI 1.49–14.28).

Conclusion:  Efforts to improve the QOL of patients with schizophrenia in this environment should encompass the identified variables. Larger, longitudinal and multi‐centred studies are needed to adequately identify factors predicting QOL in this environment.
Ridge augmentation and maxillary sinus grafting with a biphasic calcium phosphate: histologic and histomorphometric observations
Authors: Friedmann Anton , Dard Michel , Kleber Bernd‐Michael , Bernimoulin Jean‐Pierre , Bosshardt Dieter D.
Published: April 2009

Objectives: This retrospective study reports on histologic and histomorphometric observations performed on human biopsies harvested from sites augmented exclusively by biphasic calcium phosphate [BCP: hydroxyapatite (HA)/ tricalcium phosphate (TCP) 60/40] and healed for a minimum of 6 months.

Materials and methods: Five patients benefited from three augmentation regimens (i.e.: one‐stage lateral augmentation; two‐stage lateral augmentation; and two‐stage sinus grafting). In all patients, a degradable collagen membrane served as a cell‐occlusive barrier. Core biopsies were obtained from lateral as from crestal aspects 6–10 months after augmentation surgeries. For histologic and histomorphometric evaluations, the non‐decalcified tissue processing was performed.

Results: The histological examination of 11 biopsies showed graft particles frequently being bridged by the new bone, and a close contact between the graft particles and newly formed bone was seen in all samples. The mean percentages of newly formed bone, soft tissue compartment, and graft material were 38.8% (±5.89%), 41.75% (±6.08%), and 19.63% (±4.85%), respectively. Regarding bone‐to‐graft contact values, the percentage of bone coverage of graft particles for all biopsies ranged from 27.83% to 80.17%. The mean percentage of bone coverage was 55.39% (±13.03%).

Conclusions: Data from the present study demonstrated osteoconductivity scores for the BCP material (HA/TCP 60/40) in patients resembling those previously shown for grafting materials of xenogenic and alloplastic origin.
Early N‐terminal pro‐brain natriuretic peptide measurements predict clinically significant ductus arteriosus in preterm infants
Authors: Ramakrishnan S , Heung YM , Round J , Morris TP , Collinson P , Williams AF
Published: April 2009

We report a blinded, prospective study of the diagnostic utility of N‐terminal pro‐brain natriuretic peptide (NTproBNP) measurements for predicting clinically significant patent ductus arteriosus (PDA) and assessing closure.

Methods:  Plasma NTproBNP was measured during the first week in 100 preterm babies (mean gestation 28.8 ± 2.9 weeks; mean birth weight 1224 ± 512 g). Echocardiography was performed between days 5 and 7 by operators, blinded to NTproBNP concentration.

Results: NTproBNP peaked on days 2 and 3, declined by day 7. Twenty babies, later treated for PDA, had significantly higher NTproBNP levels throughout. Areas under receiver operating characteristic (ROC) curves were 0.896, 0.897 and 0.931 on days 2, 3 and 7, respectively (p < 0.0001). A concentration > 2850 pmol/L had diagnostic sensitivity of 90% and specificity of 89% (95% CI: 68, 99; likelihood ratio 8.10). Ductal closure was associated with a fall in mean NTproBNP from 3003 to 839 pmol/L (p < 0.001).

Conclusion:  N‐terminal pro B‐type brain natriuretic peptide (NTproBNP) concentrations peaked and then declined in the first week but remained higher in preterm babies whose PDA required treatment. NTproBNP on day 3 predicted whether a neonatal physician blinded to results would treat a PDA. Fall in plasma NTproBNP indicated closure.
Costs of neonatal care for low‐birthweight babies in English hospitals
Authors: Mistry Hema , Dowie Robin , Franklin Rodney CG , Jani Bhavdeep R
Published: April 2009

Aim:  To estimate mean costs of neonatal care for babies with birthweights ≤1800 g in a regional Level 3 unit and three Level 2 units providing short‐term intensive care.

Method:  Babies ≤1800 g admitted to units in four hospitals in England over 15 months in 2001–2002 were audited until discharge. Unit costs (2005–2006 prices) were attributed to their resource items, including neonatal cot occupancy, pharmaceuticals, blood products and ambulance transfers. Bootstrapped mean costs were derived for the Level 3 unit and the Level 2 units combined.

Results:  The mean gestation period for 199 Level 3 babies was 29.5 weeks compared with 30.4 weeks for 192 Level 2 babies (p = 0.003). Mean costs excluding ambulance journeys were £17  861 per Level 3 baby and £12  344 per Level 2 baby. Level 3 babies <1000 g averaged £26  815, whereas Level 2 babies <1000 g were generally less costly than babies 1000–1499 g. Ambulances transported 76 Level 3 babies and 62 Level 2 babies; their adjusted mean costs were £18  495 and £12  881, respectively.

Conclusion:  By comprehensively costing resource components, the magnitude of total costs for low‐birthweight babies has been revealed, thus demonstrating the importance of budgets for neonatal units being realistically determined by commissioners of neonatal services.
Work Interruptions and Their Contribution to Medication Administration Errors: An Evidence Review
Authors: Biron Alain D. , Loiselle Carmen G. , Lavoie‐Tremblay Mélanie
Published: April 2009

Background: In many surveys, nurses cite work interruptions as a significant contributor to medication administration errors.

Objectives: To review the evidence on (1) nurses' interruption rates, (2) characteristics of such work interruptions, and (3) contribution of work interruptions to medication administration errors.

Approach: Search strategy: CINHAL (1982–2008), MEDLINE (1980–2008), EMBASE (1980–2008), and PSYCINFO (1980–2008) were searched using a combination of keywords and reference lists. Selection criteria: Original studies published in English using nurses as participants and for which work interruption frequencies are reported. Data collection and analysis: Studies were identified and selected by two reviewers. Once selected, a single reviewer extracted data and assessed quality based on established criteria. Data on nurses' work interruption rates were synthesized to produce a pooled estimate.

Results: Twenty‐three studies were considered for analysis. A rate of 6.7 work interruptions per hour was obtained, based on 14 studies that reported both an observation time and work interruption frequency. Work interruptions are mostly initiated by nurses themselves through face‐to‐face interactions and are of short duration. A lower proportion of interruptions resulted from work system failures such as missing medication. One nonexperimental study documented the contribution of work interruptions to medication administration errors with evidence of a significant association (p = 0.01) when errors related to time of administration are excluded from the analysis. Conceptual shortcomings were noted in a majority of reviewed studies, which included the absence of theoretical underpinnings and a diversity of definitions of work interruptions.

Conclusions: Future studies should demonstrate improved methodological rigor through a precise definition of work interruptions and reliability reporting to document work interruption characteristics and their potential contribution to medication administration errors, considering the limited evidence found. Meanwhile, efforts should be made to reduce the number of work interruptions experienced by nurses.
Near Zero Shrinkage of an Low‐Temperature Co‐Fired Ceramic Package by Constrained Sintering Using Screen Printed Alumina Paste
Authors: Lee Sang Myoung , Yoo Myong Jae , Park Seong Dae , Park Jong Chul , Nahm Sahn
Published: April 2009

Conventional free sintering of low‐temperature co‐firing ceramic (LTCC) technology has several merits such as sintering temperature below 1000°C that enables co‐firing with electrode materials of silver or copper metal and multilayer structure formation. But due to the free sintering process, large shrinkage occurs. To fabricate electronic devices and components with near zero shrinkage within x, y directions constrained sintering (CS) technology is required. In this study a constrained sintering paste (CSP) utilizing alumina powder, which has a higher sintering temperature than LTCC powders, was fabricated for CS technology. The effect of CSP formulated using alumina powder on shrinkage was studied according to variation in paste composition. As a result ceramic package structure with a cavity was fabricated with shrinkage control of 0.028%, which is far smaller than the current CS technology shrinkage of approximately 0.1%.
Is the Milky Way ringing? The hunt for high-velocity streams
Authors: Minchev I. , Quillen A. C. , Williams M. , Freeman K. C. , Nordhaus J. , Siebert A. , Bienaymé O.
Published: April 2009

We perform numerical simulations of a stellar galactic disc with initial conditions chosen to represent an unrelaxed population which might have been left following a merger. Stars are unevenly distributed in radial action angle, though the disc is axisymmetric. The velocity distribution in the simulated solar neighbourhood exhibits waves travelling in the direction of positive v, where u, v are the radial and tangential velocity components. As the system relaxes and structure wraps in phase space, the features seen in the u–v plane move closer together. We show that these results can be obtained also by a semi-analytical method. We propose that this model could provide an explanation for the high-velocity streams seen in the solar neighbourhood at approximate v in kms−1, of −60 (HR1614), −80, −100 (Arcturus) and −160. In addition, we predict four new features at v≈−140, −120, 40 and 60kms−1. By matching the number and positions of the observed streams, we estimate that the Milky Way disc was strongly perturbed ∼1.9Gyr ago. This event could have been associated with Galactic bar formation.
The merger-driven evolution of warm infrared luminous galaxies
Authors: Younger Joshua D. , Hayward Christopher C. , Narayanan Desika , Cox T. J. , Hernquist Lars , Jonsson Patrik
Published: April 2009

AbstracT

We present a merger-driven evolutionary model for the production of luminous (LIRGs) and ultraluminous infrared galaxies (ULIRGs) with warm infrared (IR) colours. Our results show that simulations of gas-rich major mergers including star formation, black hole growth and feedback can produce warm (U)LIRGs. We also find that while the warm evolutionary phase is associated with increased active galactic nucleus (AGN) activity, star formation alone may be sufficient to produce warm IR colours. However, the transition can be suppressed entirely – even when there is a significant AGN contribution – when we assume a single-phase interstellar medium, which maximizes the attenuation. Finally, our evolutionary models are consistent with the 25-to-60 µm flux density ratio versus LHX/LIR relation for local LIRGs and ULIRGs, and predict the observed scatter in IR colour at fixed LHX/LIR. Therefore, our models suggest a cautionary note in the interpretation of warm IR colours: while associated with periods of active black hole growth, they are probably produced by a complex mix of star formation and AGN activity intermediate between the cold star formation dominated phase and the birth of a bright, unobscured quasar.
EFFECT OF PRICKLY PEAR (OPUNTIA FICUS‐INDICA) AND ALGARROBO (PROSOPIS SPP.) POD SYRUP COATINGS ON THE SENSORY AND CHEMICAL STABILITY IN ROASTED PEANUT PRODUCTS
Authors: MESTRALLET MARTA G. , NEPOTE VALERIA , QUIROGA PATRICIA R. , GROSSO NELSON R.
Published: April 2009

The purpose of this work was to determine the oxidative stability of roasted peanuts coated with prickly pear and algarrobo pod syrups. General composition, total phenolic compounds and radical scavenging activity were determined on prickly pear and algarrobo pod syrups. Chemical (peroxide value) and descriptive analyses were performed on samples of roasted peanuts, roasted peanuts with prickly pear syrup and roasted peanuts with algarrobo pod syrup stored at 23C for 112 days to determine protective effect of the syrup coating on the product stability. Prickly pear syrup showed higher moisture, protein, ash, lipid, phenolic compound content and lower carbohydrate content than algarrobo pod syrup. Prickly pear syrup also showed higher antioxidant activity (diphenyl picryl hydrazyl inhibition). Peroxide value, oxidized and cardboard intensity flavors increased and roasted peanutty intensity attribute decreased across the storage time for all studied products. Therefore, the addition of syrup coating provided protection against lipid oxidation. Peroxide value reached 10 meqO2/kg after 8.5 days in roasted peanuts, 20.7 days in roasted peanuts coated with prickly pear syrup and 29.5 days in roasted peanuts coated with algarrobo pod syrup at 23C. In consequence, algarrobo pod syrup had the highest protective effect in the roasted peanut product stored at room temperature.

PRACTICAL APPLICATIONS

The results of this work show advantages for using coatings that improve the stability of peanut products by making it more resistant to lipid oxidation and the development of rancid flavor. In this case, the edible coatings are elaborated using prickly pear and algarrobo pod syrups. These syrups could be applied on other similar food products with high lipid content to increase their shelf life and improve their stability, thus preventing loss of their sensory and nutritional quality.
The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans
Authors: Sakuma K. , Watanabe K. , Hotta N. , Koike T. , Ishida K. , Katayama K. , Akima H.
Published: April 2009

Aim:  To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF‐linked (RhoA, RhoGDI, STARS and SRF), myostatin‐linked (myostatin, Smad2, Smad3 and FLRG) and Foxo‐linked (P‐Akt, Foxo1, Foxo3a and Atrogin‐1) mediators.

Methods:  A single lower limb of each of eight healthy men was suspended for 20 days. Biopsy specimens were obtained from the vastus lateralis muscle pre‐ and post‐suspension.

Results:  The volume of the vastus lateralis muscle was significantly decreased after unloading. The amount of RhoA, RhoGDI or SRF protein in the muscle was not significantly changed post‐suspension. An RT‐PCR semiquantitative analysis showed increased levels of myostatin mRNA but not Smad2, Smad3 or FLRG mRNA. Unloading did not elicit significant changes in the amount of p‐Smad3 or myostatin protein in the muscle. The amount of p‐Akt protein was markedly reduced in the unloaded muscle. Lower limb suspension did not influence the expression pattern of Foxo1, Foxo3a or Atrogin‐1.

Conclusion:  Unloading inducing a mild degree of muscle atrophy may decrease p‐Akt and increase myostatin but not SRF‐linked mediators.
Can we see a cohort effect on survival of Steller sea lions (Eumetopias jubatus) at Kozlova Cape rookery (eastern Kamchatka, Russia)?
Authors: Burdin Alexander M. , Hennen Daniel R. , Calkins Donald G. , Burkanov Vladimir N. , Nikulin Victor S. , Lisitsina Tatiana Yu.
Published: April 2009

Abstract

Steller sea lions (Eumetopias jubatus) have experienced a decline in Russia as well as the United States. The causes for the decline of the Russian population may or may not overlap the causes of the decline in Alaska. The demographics of the Russian population are not well understood and are an area of interest for scientists wishing to compare and contrast the Alaskan and Russian stocks. This study uses a unique observational system to assess survival by age at a small rookery on the Kamchatka Peninsula, Kozlova Cape. We proceeded under the hypothesis that changes in environmental conditions between years would produce noticeable differences in survival of pups born in those years. We found no evidence to support our hypothesis, but did find some differences from the Alaskan population in estimated survival for the juvenile stage class. This study also provides some of the history of Steller sea lions in Russia for context.
Assessment of inhaled corticosteroid treatment response in asthma using hypertonic histamine challenge‐induced cough
Authors: Purokivi Minna , Koskela Heikki , Koistinen Tiina , Peuhkurinen Keijo , Kontra Kirsi Maarit
Published: April 2009

Background and Aims:  Bronchial provocation tests may be utilised to monitor the efficacy of the corticosteroid treatment. Unfortunately, these measurements necessitate good patient cooperation during the spirometry. Coughing during such tests is related to the degree of the bronchoconstriction and occurs involuntarily, i.e. independent of patient cooperation. This study aimed to evaluate the utility of a hypertonic histamine challenge‐induced cough in assessing the efficacy of inhaled corticosteroid treatment.

Methods:  A total of 16 steroid‐naïve asthmatics and 10 non‐asthmatic, symptomatic controls received 800‐µg beclomethasone (Beclomet Easyhaler®, Orion Ltd., Orion Pharma, Helsinki, Finland) via powder inhaler per day for 8 weeks. Videoed inhalation challenge with hypertonic histamine solution was performed before and after the treatment. Symptom questionnaire was completed before both challenges. The airway responsiveness to hypertonic histamine was expressed as the cumulative number of coughs divided by the final histamine concentration administered [coughs/concentration ratio (CCR)] and as the provocative concentration of histamine to induce a 20% fall in FEV1(PC20).

Results:  CCR [geometric mean; 95% confidence interval (CI)] of the asthmatic subjects decreased from 494 (209–1168) to 73.6 (29.8–182) coughs per mg/mL (P = 0.002). Their PC20 levels were 1.31 (1.07–1.60) and 1.91 (1.33–2.74) mg/mL over the treatment period (P = 0.01). The symptom frequency also decreased significantly in the asthmatics (P = 0.039). There were no significant changes in PC20 level, in CCR level or in symptom frequency in non‐asthmatic subjects during the treatment.

Conclusions:  Hypertonic histamine challenge‐induced cough and PC20 are sensitive measures in assessing the treatment effect in asthma. The cough response may be especially useful in subjects who cannot perform spirometry reliably.

Please cite this paper as: Purokivi M, Koskela H, Koistinen T, Peuhkurinen K and Kontra KM. Assessment of inhaled corticosteroid treatment response in asthma using hypertonic histamine challenge‐induced cough. The Clinical Respiratory Journal 2010; 4: 67–73.
Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits
Authors: Loftsson Thorsteinn , Thorisdóttir Sigridur , Fridriksdóttir Hafrun , Stefánsson Einar
Published: April 2009

Purpose:  This study aimed to develop low‐viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits.

Methods:  Aqueous eyedrops with hydroxypropyl‐β‐cyclodextrin containing 0.01–2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg).

Results:  Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf‐life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10–22 hours after administration and duration of up to 32 hours.

Conclusions:  Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low‐viscosity aqueous eyedrop formulations.
The changing balance of brainstem–spinal cord modulation of pain processing over the first weeks of rat postnatal life
Authors: Hathway G. J. , Koch S. , Low L. , Fitzgerald M.
Published: April 2009

Brainstem–spinal cord connections play an essential role in adult pain processing, and the modulation of spinal pain network excitability by brainstem nuclei is known to contribute to hyperalgesia and chronic pain. Less well understood is the role of descending brainstem pathways in young animals when pain networks are more excitable and exposure to injury and stress can lead to permanent modulation of pain processing. Here we show that up to postnatal day 21 (P21) in the rat, the rostroventral medulla of the brainstem (RVM) exclusively facilitates spinal pain transmission but that after this age (P28 to adult), the influence of the RVM shifts to biphasic facilitation and inhibition. Graded electrical microstimulation of the RVM at different postnatal ages revealed a robust shift in the balance of descending control of both spinal nociceptive flexion reflex EMG activity and individual dorsal horn neuron firing properties, from excitation to inhibition, beginning after P21. The shift in polarity of descending control was also observed following excitotoxic lesions of the RVM in adult and P21 rats. In adults, RVM lesions decreased behavioural mechanical sensory reflex thresholds, whereas the same lesion in P21 rats increased thresholds. These data demonstrate, for the first time, the changing postnatal influence of the RVM in spinal nociception and highlight the central role of descending brainstem control in the maturation of pain processing.
Mechanisms underlying short‐term modulation of transmitter release by presynaptic depolarization
Authors: Hori Tetsuya , Takahashi Tomoyuki
Published: April 2009

Presynaptic terminal depolarization modulates the efficacy of transmitter release. Residual Ca2+ remaining after presynaptic depolarization is thought to play a critical role in facilitation of transmitter release, but its downstream mechanism remains unclear. By making simultaneous pre‐ and postsynaptic recordings at the rodent calyx of Held synapse, we have investigated mechanisms involved in the facilitation and depression of postsynaptic currents induced by presynaptic depolarization. In voltage‐clamp experiments, cancellation of the Ca2+‐dependent presynaptic Ca2+ current (IpCa) facilitation revealed that this mechanism can account for 50% of postsynaptic current facilitation, irrespective of intraterminal EGTA concentrations. Intraterminal EGTA, loaded at 10 mm, failed to block postsynaptic current facilitation, but additional BAPTA at 1 mm abolished it. Potassium‐induced sustained depolarization of non‐dialysed presynaptic terminals caused a facilitation of postsynaptic currents, superimposed on a depression, with the latter resulting from reductions in presynaptic action potential amplitude and number of releasable vesicles. We conclude that presynaptic depolarization bidirectionally modulates transmitter release, and that the residual Ca2+ mechanism for synaptic facilitation operates in the immediate vicinity of voltage‐gated Ca2+ channels in the nerve terminal.
Decreased microvascular vasomotion and myogenic response in rat skeletal muscle in association with acute insulin resistance
Authors: Newman John M. B. , Dwyer Renee M. , St‐Pierre Philippe , Richards Stephen M. , Clark Michael G. , Rattigan Stephen
Published: April 2009

In addition to increased glucose uptake, insulin action is associated with increased total and microvascular blood flow, and vasomotion in skeletal muscle. The aim of this study was to determine the effect of acute insulin resistance caused by the peripheral vasoconstrictor α‐methylserotonin (αMT) on microvascular vasomotion in muscle. Heart rate (HR), mean arterial pressure (MAP), femoral blood flow (FBF), whole body glucose infusion (GIR) and hindleg glucose uptake (HGU) were determined during control and hyperinsulinaemic euglycaemic clamp conditions in anaesthetized rats receiving αMT infusion. Changes in muscle microvascular perfusion were measured by laser Doppler flowmetry (LDF) and vasomotion was assessed by applying wavelet analysis to the LDF signal. Insulin increased GIR and HGU. Five frequency bands corresponding to cardiac, respiratory, myogenic, neurogenic and endothelial activities were detected in the LDF signal. Insulin infusion alone increased FBF (1.18 ± 0.10 to 1.78 ± 0.12 ml min–1, P < 0.05), LDF signal strength (by 16% compared to baseline) and the relative amplitude of the myogenic component of vasomotion (0.89 ± 0.09 to 1.18 ± 0.06, P < 0.05). When infused alone αMT decreased LDF signal strength and the myogenic component of vasomotion by 23% and 27% respectively compared to baseline, but did not affect HGU or FBF. Infusion of αMT during the insulin clamp decreased the stimulatory effects of insulin on GIR, HGU, FBF and LDF signal and blocked the myogenic component of vasomotion. These data suggest that insulin action to recruit microvascular flow may in part involve action on the vascular smooth muscle to increase vasomotion in skeletal muscle to thereby enhance perfusion and glucose uptake. These processes are impaired with this model of αMT‐induced acute insulin resistance.
Relationship between nucleotide binding and ion channel gating in cystic fibrosis transmembrane conductance regulator
Authors: Aleksandrov Andrei A. , Cui Liying , Riordan John R.
Published: April 2009

We have employed rate‐equilibrium free energy relationship (REFER) analysis to characterize the dynamic events involved in the allosteric regulation of cystic fibrosis transmembrane conductance regulator (CFTR) function. A wide range of different hydrolysable and poorly hydrolysable nucleoside triphosphates were used to elucidate the role of ATP hydrolysis in CFTR function. The linearity of the REFER plots and Φ values near unity for all ligands tested implies that CFTR channel gating is a reversible thermally driven process with all structural reorganization in the binding site(s) completed prior to channel opening. This is consistent with the requirement for nucleotide binding for channel opening. However, the channel structural transition from the open to the closed state occurs independently of any events in the binding sites. Similar results were obtained on substitution of amino acids at coupling joints between both nucleotide binding domains (NBD) and cytoplasmic loops (CL) in opposite halves of the protein, indicating that any structural reorganization there also had occurred in the channel closed state. The fact that fractional Φ values were not observed in either of these distant sites suggests that there may not be a deterministic ‘lever‐arm’ mechanism acting between nucleotide binding sites and the channel gate. These findings favour a stochastic coupling between binding and gating in which all structural transitions are thermally driven processes. We speculate that increase of channel open state probability is due to reduction of the number of the closed state configurations available after physical interaction between ligand bound NBDs and the channel.
Revisiting synaptic vesicle pool localization in the Drosophila neuromuscular junction
Authors: Denker Annette , Kröhnert Katharina , Rizzoli Silvio O.
Published: April 2009

The synaptic vesicles are organized in distinct populations or ‘pools’: the readily releasable pool (the first vesicles released upon stimulation), the recycling pool (which maintains release under moderate stimulation) and the reserve pool (which is called into action only upon strong, often unphysiological stimulation). A major question in the field is whether the pools consist of biochemically different vesicles or whether the pool tag is a spatial one (with the recycling vesicles found next to the release sites, and the reserve ones farther away). A strong and stable spatial segregation has been proposed in the last decade in the Drosophila larval neuromuscular junction – albeit based solely on light microscopy experiments. We have tested here this hypothesis using electron microscopy (EM) photoconversion. We found the recycling and reserve pools to be thoroughly intermixed at the EM level, indicating that spatial location is irrelevant for the functional properties of the vesicle.
Minor sarcoplasmic reticulum membrane components that modulate excitation–contraction coupling in striated muscles
Authors: Treves Susan , Vukcevic Mirko , Maj Marcin , Thurnheer Raphael , Mosca Barbara , Zorzato Francesco
Published: April 2009

In striated muscle, activation of contraction is initiated by membrane depolarisation caused by an action potential, which triggers the release of Ca2+ stored in the sarcoplasmic reticulum by a process called excitation–contraction coupling. Excitation–contraction coupling occurs via a highly sophisticated supramolecular signalling complex at the junction between the sarcoplasmic reticulum and the transverse tubules. It is generally accepted that the core components of the excitation–contraction coupling machinery are the dihydropyridine receptors, ryanodine receptors and calsequestrin, which serve as voltage sensor, Ca2+ release channel, and Ca2+ storage protein, respectively. Nevertheless, a number of additional proteins have been shown to be essential both for the structural formation of the machinery involved in excitation–contraction coupling and for its fine tuning. In this review we discuss the functional role of minor sarcoplasmic reticulum protein components. The definition of their roles in excitation–contraction coupling is important in order to understand how mutations in genes involved in Ca2+ signalling cause neuromuscular disorders.
Triadin: what possible function 20 years later?
Authors: Marty Isabelle , Fauré Julien , Fourest‐Lieuvin Anne , Vassilopoulos Stéphane , Oddoux Sarah , Brocard Julie
Published: April 2009

During the last 20 years, the identification of triadin function in cardiac and skeletal muscle has been the focus of numerous studies. First thought of as the missing link between the ryanodine receptor and the dihydropyridine receptor and responsible of skeletal type excitation–contraction coupling, the current hypothesis on triadin function has slowly evolved, and triadin is envisaged now as a regulator of calcium release, both in cardiac and skeletal muscle. Nevertheless, none of the experiments performed up to now has given a clear cut view of what triadin really does in muscle. The problem became more complex with the identification of multiple triadin isoforms, having possibly multiple functions. Using a different approach from what has been done previously, we have obtained new clues about the function of triadin. Our data point to a possible involvement of triadin in reticulum structure, in relation with the microtubule network.
Deconstructing calsequestrin. Complex buffering in the calcium store of skeletal muscle
Authors: Royer Leandro , Ríos Eduardo
Published: April 2009

Since its discovery in 1971, calsequestrin has been recognized as the main Ca2+ binding protein inside the sarcoplasmic reticulum (SR), the organelle that stores and upon demand mobilizes Ca2+ for contractile activation of muscle. This article reviews the potential roles of calsequestrin in excitation–contraction coupling of skeletal muscle. It first considers the quantitative demands for a structure that binds Ca2+ inside the SR in view of the amounts of the ion that must be mobilized to elicit muscle contraction. It briefly discusses existing evidence, largely gathered in cardiac muscle, of two roles for calsequestrin: as Ca2+ reservoir and as modulator of the activity of Ca2+ release channels, and then considers the results of an incipient body of work that manipulates the cellular endowment of calsequestrin. The observations include evidence that both the Ca2+ buffering capacity of calsequestrin in solution and that of the SR in intact cells decay as the free Ca2+ concentration is lowered. Together with puzzling observations of increase of Ca2+ inside the SR, in cells or vesicular fractions, upon activation of Ca2+ release, this is interpreted as evidence that the Ca2+ buffering in the SR is non‐linear, and is optimized for support of Ca2+ release at the physiological levels of SR Ca2+ concentration. Such non‐linearity of buffering is qualitatively explained by a speculation that puts together ideas first proposed by others. The speculation pictures calsequestrin polymers as ‘wires’ that both bind Ca2+ and efficiently deliver it near the release channels. In spite of the kinetic changes, the functional studies reveal that cells devoid of calsequestrin are still capable of releasing large amounts of Ca2+ into the myoplasm, consistent with the long term viability and apparent good health of mice engineered for calsequestrin ablation. The experiments therefore suggest that other molecules are capable of providing sites for reversible binding of large amounts of Ca2+ inside the sarcoplasmic reticulum.
Tumour necrosis factor α activates nuclear factor κB signalling to reduce N‐type voltage‐gated Ca2+ current in postganglionic sympathetic neurons
Authors: Motagally Mohamed A. , Lukewich Mark K. , Chisholm Susan P. , Neshat Shadia , Lomax Alan E.
Published: April 2009

Inflammation has profound effects on the innervation of affected tissues, including altered neuronal excitability and neurotransmitter release. As Ca2+ influx through voltage‐gated Ca2+ channels (VGCCs) is a critical determinant of excitation–secretion coupling in nerve terminals, the aim of this study was to characterize the effect of overnight incubation in the inflammatory mediator tumour necrosis factor α (TNFα; 1 nm) on VGCCs in dissociated neurons from mouse superior mesenteric ganglia (SMG). Voltage‐gated Ca2+ currents (ICa) were measured using the perforated patch clamp technique and the VGCC subtypes present in SMG neurons were estimated based on inhibition by selective VGCC blockers: ω‐conotoxin GVIA (300 nm; N‐type), nifedipine (10 μm; L‐type), and ω‐conotoxin MVIIC (300 nm; N‐, P/Q‐type). We used intracellular Ca2+ imaging with Fura‐2 AM to compare Ca2+ influx during depolarizations in control and TNFα‐treated neurons. TNF receptor and VGCC mRNA expression were measured using PCR, and channel α subunit (CaV2.2) was localized with immunohistochemistry. Incubation in TNFα significantly decreased ICa amplitude and depolarization‐induced Ca2+ influx. The reduction in ICa was limited to ω‐conotoxin GVIA‐sensitive N‐type Ca2+ channels. Depletion of glial cells by incubation in cytosine arabinoside (5 μm) did not affect ICa inhibition by TNFα. Preincubation of neurons with SC‐514 (20 μm) or BAY 11‐7082 (1 μm), which both inhibit nuclear factor κB signalling, prevented the reduction in ICa by TNFα. Inhibition of N‐type VGCCs following TNFα incubation was associated with a decrease in CaV2.2 mRNA and reduced membrane localization of CaV2.2 immunoreactivity. These data suggest that TNFα inhibits ICa in SMG neurons and identify a novel role for NF‐κB in the regulation of neurotransmitter release during inflammatory conditions with elevated circulating TNFα, such as Crohn's disease and Guillain‐Barré syndrome.
Separate signalling mechanisms underlie mGluR1 modulation of leak channels and NMDA receptors in the network underlying locomotion
Authors: Nanou Evanthia , Kyriakatos Alexandros , Kettunen Petronella , El Manira Abdeljabbar
Published: April 2009

Metabotropic glutamate receptor subtype 1 (mGluR1) contributes importantly to the activity of the spinal locomotor network. For example, it potentiates NMDA current and inhibits leak conductance in lamprey spinal cord neurons. In this study we examined the signalling pathways underlying the mGluR1 modulation of NMDA receptors and leak channels, respectively. Our results show that mGluR1‐induced potentiation of NMDA current required activation of phospholipase C (PLC) and was independent of the increase in the intracellular Ca2+ concentration because it was unaffected by the Ca2+ chelator BAPTA and by depletion of the internal Ca2+ stores with thapsigargin. We also show that the mGluR1‐mediated inhibition of leak channels is mediated by activation of G‐proteins. Finally, we show that blockade of protein kinase C (PKC) abolished the mGluR1‐induced inhibition of leak current without affecting the potentiation of NMDA receptors. The contribution of mGluR1‐mediated modulation of leak channels to the potentiation of the locomotor cycle frequency was assessed during fictive locomotion. Blockade of PKC significantly decreased the short‐term potentiation of locomotor cycle frequency by mGluR1. These results show that the effects of mGluR1 activation on the two cellular targets, the NMDA receptor and leak channels, are mediated through separate signalling pathways.
Altered firing pattern of single‐unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure
Authors: Murai Hisayoshi , Takamura Masayuki , Maruyama Michirou , Nakano Manabu , Ikeda Tatsunori , Kobayashi Daisuke , Otowa Kan‐ichi , Ootsuji Hiroshi , Okajima Masaki , Furusho Hiroshi , Takata Shigeo , Kaneko Shuichi
Published: April 2009

Sympathetic activation in chronic heart failure (CHF) is greatly augmented at rest but the response to exercise remains controversial. We previously demonstrated that single‐unit muscle sympathetic nerve activity (MSNA) provides a more detailed description of the sympathetic response to physiological stress than multi‐unit nerve recordings. The purpose of this study was to determine whether the reflex response and discharge properties of single‐unit MSNA are altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3 min) in CHF patients (New York Heart Association functional class II or III, n= 16) compared with age‐matched healthy control subjects (n= 13). At rest, both single‐unit and multi‐unit indices of sympathetic outflow were augmented in CHF compared with controls (P < 0.05). However, the percentage of cardiac intervals that contained one, two, three or four single‐unit spikes were not different between the groups. Compared to the control group, HG elicited a larger increase in multi‐unit total MSNA (Δ1002 ± 50 compared with Δ636 ± 76 units min−1, P < 0.05) and single‐unit MSNA spike incidence (Δ27 ± 5 compared with Δ8 ± 2 spikes (100 heart beats)–1), P < 0.01) in the CHF patients. More importantly, the percentage of cardiac intervals that contained two or three single‐unit spikes was increased (P < 0.05) during exercise in the CHF group only (Δ8 ± 2% and Δ5 ± 1% for two and three spikes, respectively). These results suggest that the larger multi‐unit total MSNA response observed during HG in CHF is brought about in part by an increase in the probability of multiple firing of single‐unit sympathetic neurones.
Mast cell‐cholinergic nerve interaction in mouse airways
Authors: Weigand Letitia A. , Myers Allen C. , Meeker Sonya , Undem Bradley J.
Published: April 2009

We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 μg ml−1) caused histamine release (∼70% total tissue content), and smooth muscle contraction that was rapid in onset and short‐lived (t1/2< 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5‐HT, and responses to both OVA and 5‐HT were sensitive to 10 μm‐ketanserin (5‐HT2receptor antagonist) and strongly inhibited by atropine (1 μm). Epithelial denudation had no effect on the OVA‐induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5‐HT. There were virtually no mast cells in the mast cell‐deficient (sash−/−) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell‐deficient (sash−/−) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin‐sensitive 5‐HT‐induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen‐induced contraction of mouse trachea is epithelium‐independent, and requires mast cell‐derived 5‐HT to activate 5‐HT2receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction.
Off-Design Performance of a Single-Stage Transonic Turbine
Authors: Woinowsky-Krieger M. , Lavoie J.-P. , Vlasic E. P. , Moustapha S. H.
Published: April 2009

This paper presents results of rig testing of a transonic, single-stage turbine at off-design conditions. Mapping of the 3.4 pressure ratio, 1.9 stage loading turbine ranged from 70 through 120 percent of design speed and 75 to 125 percent of design pressure ratio. Results show expansion efficiency dropping over 4 percent from 100 to 80 percent of design speed at design pressure ratio, while remaining within half a percent from 90 to 110 percent of design pressure ratio at design speed. Efficiency lapse rate from equivalent sea-level to cruise altitude Reynolds numbers at the design point was measured and found to be worth over 1.5 percent. Analyses of test results using a viscous three-dimensional solver showed very good agreement for the efficiency change with speed.
Measurement and Calculation of Nozzle Guide Vane End Wall Heat Transfer
Authors: Harvey N. W. , Rose M. G. , Coupland J. , Jones T. V.
Published: April 2009

A three-dimensional steady viscous finite volume pressure correction method for the solution of the Reynolds-averaged Navier–Stokes equations has been used to calculate the heat transfer rates on the end walls of a modern High Pressure Turbine first-stage stator. Surface heat transfer rates have been calculated at three conditions and compared with measurements made on a model of the vane tested in annular cascade in the Isentropic Light Piston Facility at DERA, Pyestock. The NGV Mach numbers, Reynolds numbers, and geometry are fully representative of engine conditions. Design condition data have previously been presented by Harvey and Jones (1990). Off-design data are presented here for the first time. In the areas of highest heat transfer, the calculated heat transfer rates are shown to be within 20 percent of the measured values at all three conditions. Particular emphasis is placed on the use of wall functions in the calculations with which relatively coarse grids (of around 140,000 nodes) can be used to keep computational run times sufficiently low for engine design purposes.
Investigation of Detailed Film Cooling Effectiveness and Heat Transfer Distributions on a Gas Turbine Airfoil
Authors: Drost U. , Bo¨lcs A.
Published: April 2009

In the present study film cooling effectiveness and heat transfer were systematically investigated on a turbine NGV airfoil employing the transient liquid crystal technique and a multiple regression procedure. Tests were conducted in a linear cascade at exit Reynolds numbers of 0.52e6, 1.02e6 and 1.45e6 and exit Mach numbers of 0.33, 0.62 and 0.8, at two mainstream turbulence intensities of 5.5 and 10 percent. The film cooling geometry consisted of a single compound angle row on the pressure side (PS), and a single or a double row on the suction side (SS). Foreign gas injection was used to obtain a density ratio of approximately 1.65, while air injection yielded a density ratio of unity. Tests were conducted for blowing ratios of 0.25 to 2.3 on the SS, and 0.55 to 7.3 on the PS. In general film cooling injection into a laminar BL showed considerably higher effectiveness in the near-hole region, as compared to a turbulent BL. While mainstream turbulence had only a weak influence on SS cooling, higher effectiveness was noted on the PS at high turbulence due to increased lateral spreading of the coolant. Effects of mainstream Mach and Reynolds number were attributed to changes of the BL thickness and flow acceleration. Higher density coolant yielded higher effectiveness on both SS and PS, whereas heat transfer ratios were increased on the SS and decreased on the PS. Comparison of the single and double row cooling configurations on the SS revealed a better film cooling performance of the double row due to an improved film coverage and delayed jet separation.
Heat Transfer in a “Cover-Plate” Preswirl Rotating-Disk System
Authors: Pilbrow R. , Karabay H. , Wilson M. , Owen J. M.
Published: April 2009

In most gas turbines, blade-cooling air is supplied from stationary preswirl nozzles that swirl the air in the direction of rotation of the turbine disk. In the “cover-plate” system, the preswirl nozzles are located radially inward of the blade-cooling holes in the disk, and the swirling airflows radially outward in the cavity between the disk and a cover-plate attached to it. In this combined computational and experimental paper, an axisymmetric elliptic solver, incorporating the Launder–Sharma and the Morse low-Reynolds-number k–ε turbulence models, is used to compute the flow and heat transfer. The computed Nusselt numbers for the heated “turbine disk” are compared with measured values obtained from a rotating-disk rig. Comparisons are presented, for a wide range of coolant flow rates, for rotational Reynolds numbers in the range 0.5 X 106 to 1.5 X 106, and for 0.9 < βp < 3.1, where βp is the preswirl ratio (or ratio of the tangential component of velocity of the cooling air at inlet to the system to that of the disk). Agreement between the computed and measured Nusselt numbers is reasonably good, particularly at the larger Reynolds numbers. A simplified numerical simulation is also conducted to show the effect of the swirl ratio and the other flow parameters on the flow and heat transfer in the cover-plate system.