bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cu2+(1,10 phenanthroline)3is an open‐channel blocker of the human skeletal muscle sodium channel
Authors: Popa Mariana Oana , Lerche Holger 
Published: January 2006

The formation of disulfide bridges is a classical approach used to study the mobility, proximity and distances of residues in a variety of proteins, including ligand‐ and voltage‐gated ion channels. We performed patch‐clamp studies to investigate the interaction of a pair of cysteines introduced into the human skeletal muscle voltage‐gated Na+channel (hNav1.4) using the oxidation catalyst, Cu2+(1,10‐phenanthroline)3(CuPhen).Our experiments resulted in a surprising finding, a reversible current inhibition of the mutant I1160C/L1482C containing two cysteines in the D3/and D4/S4–S5 loops, subjected to oxidative cross‐linking in the presence of CuPhen.We report here that CuPhen is an open channel blocker of both mutant and wild‐type (WT) hNav1.4 channels, however, for WT channels a more than 10‐fold higher concentration was needed to induce the same effect. Moreover, 1,10‐phenanthroline was capable of blocking Na+channels in the absence of Cu2+ions. Our results indicate a use‐ and voltage‐dependent binding and unbinding of CuPhen, reminiscent of the lidocaine quaternary derivative QX‐314 and the neurotoxin batrachotoxin.Care should be taken when using CuPhen as an oxidizing reagent in cross‐linking experiments, since it may directly affect channel activity. Our results identify CuPhen (and phenantroline) as a novel use‐dependent inhibitor of Na+channels, a mechanism that is shared by drugs widely used in the treatment of epilepsy, neuropathic pain, cardiac arrhythmia and myotonia. We hypothesize that I1160C in D3/S4–S5 and the corresponding L1482C mutation in D4/S4–S5 could allosterically affect a binding site located in the inner pore region of the channel.British Journal of Pharmacology(2006)147, 808–814. doi:10.1038/sj.bjp.0706667
QT Interval Measurement
Authors: Charbit Beny , Samain Emmanuel , Merckx Paul , Funck-Brentano Christian 
Published: January 2006

Background
Assessment of repolarization duration is often recommended to avoid administration of QT-prolonging drugs in patients with prolonged QTc interval, a frequent situation in the postoperative period. Bazett QT correction inappropriately increases QTc when heart rate is increased, and the use of the Fridericia formula may avoid a falsely prolonged QTc interval. The authors assessed automatic QT interval measurement to detect prolonged QTc interval (women >450 ms; men >440 ms) in the postoperative setting.

Methods
Automatic and manual electrocardiograms were performed in 108 patients after anesthesia. Automatic electrocardiographic measurement used the Bazett formula. Manual measurements were made from each electrocardiogram and used as the reference. Agreement between the two methods was analyzed. Bazett and Fridericia QT corrections were compared in this population.

Results
Agreement between automatic and manual measurements was low. The Fridericia correction, but not the Bazett correction, was independent from heart rate and allowed adequate QT correction. Sensitivity of automatic measurements to detect prolonged QTc-Bazett interval was 54%. Automatic QTc-Bazett interval less than 430 ms ruled out a manual prolonged QTc interval. When automatic QTc-Bazett was greater than 430 ms, this value was converted according to Fridericia. Automatic QTc-Fridericia greater than 430 ms identified all patients with prolonged manual QTc with a negative predictive error of 0% (95% confidence interval, 0-7%). QTc-Fridericia can be approximated by respectively adding or subtracting 5% to the uncorrected QT for each increase or decrease by 10 beats/min in heart rate from 60 beats/min.

Conclusions
Automatic QTc-Bazett measurement, if abnormal, associated with calculation of QTc-Fridericia reliably identifies patients in whom manual QTc measurement must be performed to confirm postoperative prolonged QTc interval.
Effects of General Anesthesia on Anandamide Blood Levels in Humans
Authors: Schelling Gustav , Hauer Daniela , Azad Shahnaz Christina , Schmoelz Martin , Chouker Alexander , Schmidt Michael , Hornuss Cyrill , Rippberger Markus , Briegel Josef , Thiel Manfred , Vogeser Michael 
Published: January 2006

Background
The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Endocannabinoids play an important role in the physiologic control of sleep, pain processing, and emesis. The authors therefore investigated the effects of general anesthesia on the endocannabinoid system in humans.

Methods
The authors measured whole blood levels of anandamide in 12 patients after induction of general anesthesia with etomidate (an agent shown to have no effect on anandamide levels) and maintenance of anesthesia with the volatile agent sevoflurane as well as in 12 patients undergoing total intravenous anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the mouse brain. Anandamide levels were measured using high-performance liquid chromatography-tandem mass spectrometry at four time points (before and at 10, 20, 30, and 40 min after induction of anesthesia).

Results
Patients of the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min after induction, whereas anandamide levels in patients of the propofol group remained unchanged (type III sum of squares = 1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance).

Conclusion
General anesthesia influences the endocannabinoid system in a drug-dependent way, which may explain side effects of general anesthetics such as psychomimetic and antiemetic properties of propofol and the high incidence of postoperative nausea and vomiting after volatile anesthetics. These findings suggest new targets for anesthetic drug development.
Expansion of Gas Bubbles by Nitrous Oxide and Xenon
Authors: Benavides Rodrigo , Maze Mervyn , Franks Nicholas P. 
Published: January 2006

Background
Nitrous oxide is well known to expand gas bubbles trapped in enclosed spaces and is contraindicated in situations where this may occur. Xenon, an anesthetic gas with similar physical properties to nitrous oxide, is also likely to expand gas bubbles, and it has been predicted that microbubbles in the circulation may expand dramatically when exposed to xenon. Because of the possibility that xenon will be used during cardiopulmonary bypass surgery, a procedure that is likely to introduce microbubbles into the circulation, the authors reinvestigated the extent to which xenon expands gas bubbles in aqueous solution.

Methods
Gas bubbles of either air or oxygen were formed in an aqueous solution, and their size was monitored using optical microscopy when they were exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen mixture.

Results
Both nitrous oxide and xenon rapidly expanded air bubbles, although nitrous oxide caused a much larger expansion. The observed expansion was not greatly dependent on the initial size of the bubble but was significantly greater at lower temperatures. Under conditions relevant to cardiopulmonary bypass surgery (50% xenon-50% oxygen, 30 degrees C), the increase in diameter was modest (9.7 +/- 0.8%).

Conclusions
Although xenon does expand small air and oxygen bubbles, the extent to which this occurs under clinically relevant conditions of concentration and temperature is modest.
Increased Expression of Cyclooxygenase and Nitric Oxide Isoforms, and Exaggerated Sensitivity to Prostaglandin E2, in the Rat Lumbar Spinal Cord 3 Days after L5–L6 Spinal Nerve Ligation
Authors: O’Rielly Darren D. , Loomis Christopher W. 
Published: January 2006

Background
Spinal prostaglandins seem to be important in the early pathogenesis of experimental neuropathic pain. Here, the authors investigated changes in the expression of cyclooxygenase and nitric oxide synthase (NOS) isoforms in the lumbar, thoracic, and cervical spinal cord and the pharmacologic sensitivity to spinal prostaglandin E2 (PGE2) after L5-L6 spinal nerve ligation (SNL).

Methods
Male Sprague-Dawley rats, fitted with intrathecal catheters, underwent SNL or sham surgery 3 days before experimentation. Paw withdrawal threshold was monitored for up to 20 days. Immunoblotting, spinal glutamate release, and behavioral testing were examined 3 days after SNL.

Results
Allodynia (paw withdrawal threshold < or = 4 g) was evident 1 day after SNL and remained stable for 20 days. Paw withdrawal threshold was unchanged (P > 0.05) from baseline (> 15 g) after sham surgery except for a small but significant decrease on day 20. Cyclooxygenase 2, neuronal NOS, and inducible NOS were significantly increased in the ipsilateral lumbar dorsal horn after SNL. Expression in the contralateral dorsal horn and ventral horns (lumbar segments) or bilaterally (thoracic and cervical segments) was unchanged from sham controls. This was accompanied by a significant decrease in both the EC50 of PGE2-evoked glutamate release and the ED50 of PGE2 on brush-evoked allodynia. Enhanced sensitivity to PGE2 was localized to lumbar segments of SNL animals and attenuated by SC-51322 or S(+)-ibuprofen, but not R(-)-ibuprofen (100 mum).

Conclusion
The increased expression of cyclooxygense-2, neuronal NOS, and inducible NOS and the enhanced sensitivity to PGE2 in spinal segments affected by SNL support the hypothesis that spinal prostanoids play an early pathogenic role in experimental neuropathic pain.
Determination of network of residues that regulate allostery in protein families using sequence analysis
Authors: Dima Ruxandra I. , Thirumalai D. 
Published: January 2006

AbstractAllosteric interactions between residues that are spatially apart and well separated in sequence are important in the function of multimeric proteins as well as single‐domain proteins. This observation suggests that, among the residues that are involved in long‐range communications, mutation at one site should affect interactions at a distant site. By adopting a sequence‐based approach, we present an automated approach that uses a generalization of the familiar sequence entropy in conjunction with a coupled two‐way clustering algorithm, to predict the network of interactions that trigger allosteric interactions in proteins. We use the method to identify the subset of dynamically important residues in three families, namely, the small PDZ family, G protein–coupled receptors (GPCR), and the Lectins, which are cell‐adhesion receptors that mediate the tethering and rolling of leukocytes on inflamed endothelium. For the PDZ and GPCR families, our procedure predicts, in agreement with previous studies, a network containing a small number of residues that are involved in their function. Application to the Lectin family reveals a network of residues interspersed throughout the C‐terminal end of the structure that are responsible for binding to ligands. Based on our results and previous studies, we propose that functional robustness requires that only a small subset of distantly connected residues be involved in transmitting allosteric signals in proteins.
Diversity: between neutrality and structure
Authors: Pueyo Salvador 
Published: January 2006

Here I present an integrated framework for species abundance distributions (SADs) that goes beyond the neutral theory without relying on complex mechanistic models. I give some general mathematical results on the relationship between SADs and their underlying dynamics, and analyse an extensive set of marine phytoplankton data in order to test the neutral theory against this broader framework.The main theoretical and empirical results are: (i) the logseries, which is the SAD produced by simple neutral models without migration, is quite robust in response to additional factors, including some forms of niche segregation; (ii) when there is a small but significant deviation from a logseries, the SAD will generally have the form of a power law, regardless of the specific mechanisms; (iii) when the deviation is moderate, the SAD will generally have the form of a lognormal, regardless of the specific mechanisms; (iv) although in a wide range of situations neutral and non‐neutral dynamics cannot be distinguished from the SAD alone, some empirical SADs do have the fingerprint of non‐neutrality: this is the case of marine dinoflagellates, in contrast to marine diatoms, which adjust to neutral theory predictions. The results for marine phytoplankton illustrate that both neutral and non‐neutral mechanisms coexist in nature, and seem to have different weights in different groups of organisms.In addition to the above findings, I discuss several related contributions and point out some important pitfalls in the literature.
A preliminary in vitro study into the use of IL‐1Ra gene therapy for the inhibition of intervertebral disc degeneration
Authors: Le Maitre Christine L. , Freemont Anthony J. , Hoyland Judith A. 
Published: January 2006

SummaryConventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL‐1 in DIVD. A natural inhibitor of IL‐1 exists, IL‐1Ra, which would be an ideal molecular target for inhibiting IL‐1‐mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL‐1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL‐1Ra gene (Ad‐IL‐1Ra) and protein production measured using an enzyme‐linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL‐1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad‐IL‐1Ra were injected into degenerate disc tissue explants and IL‐1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad‐IL‐1Ra produced elevated levels of IL‐1Ra for prolonged time periods, and these infected cells were resistant to IL‐1. When the infected cells were injected into disc explants, IL‐1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL‐1‐mediated events during disc degeneration.
A vitellogenic‐like carboxypeptidase expressed by human macrophages is localized in endoplasmic reticulum and membrane ruffles
Authors: Harris James , Schwinn Nicole , Mahoney James A. , Lin Hsi‐Hsien , Shaw Michael , Howard Chris J. , Da Silva Rosangela P. , Gordon Siamon 
Published: January 2006

AbstractCarboxypeptidase, vitellogenic‐like (CPVL) is a serine carboxypeptidase of unknown function that was first characterized in human macrophages. Initial studies suggested that CPVL is largely restricted to the monocytic lineage, although it may also be expressed by cells outside the immune system. Here, we use a new monoclonal antibody to characterize the properties and localization of CPVL in human macrophages to elucidate a possible function for the protease. CPVL is up‐regulated during the maturation of monocytes (MO) to macrophages, although the protein can be seen in both. In primary macrophages, CPVL is glycosylated with high mannose residues and colocalizes with markers for endoplasmic reticulum, while in MO it is more disperse and less clearly associated with endoplasmic reticulum. CPVL is highly expressed in lamellipodia and membrane ruffles, which also concentrate markers of the secretory pathway (MIP‐1α and tumour necrosis factor‐α) and major histocompatibility complex (MHC) class I and II molecules. CPVL can be seen on early latex bead and Candida albicans phagosomes, but it is not retained in the maturing phagosome, unlike MHC class I/II. CPVL has a mixed cytosolic and membrane‐associated localization but is not detectable on the outer plasma membrane. We propose that CPVL may be involved in antigen processing, the secretory pathway and/or in actin remodelling and lamellipodium formation.
Early and late immunohistochemical and ultrastructural changes associated with functional impairment of the lachrymal gland following external beam radiation
Authors: Hakim Samer G. , Schroder Christina , Geerling Gerd , Lauer Isabel , Wedel Thilo , Kosmehl Hartwig , Driemel Oliver , Jacobsen Hans‐Christian , Trenkle Thomas , Hermes Dirk , Sieg Peter 
Published: January 2006

SummaryThe aim of this study was to investigate scintigraphic, immunohistological and ultrastructural changes associated with radiation‐induced dysfunction of the lachrymal gland in an established experimental animal model. Ten rabbits were randomized into two groups and used for the study; in the control as well as experimental group, the Schirmer‐test, lachrymal gland scintigraphy, and immunohistological and ultrastructural investigations were carried out prior to irradiation and 72 h as well as 1 month after single‐dose irradiation with 15 Gy. Seventy‐two hours after irradiation, secretion reduction evaluated by the Schirmer‐test was evident. At this phase, we could observe a decrease in the expression of α‐SMA and a re‐distribution of tenascin‐C matrix. Ultrastructural changes of acinar and myoepithelial cells were noticed; simultaneously, disturbance in the primary 99mTcO4– uptake as well as significant reduction of the lachrymal ejection fraction was assessed scintigraphically. These changes were still evident 1 month following irradiation but became less intensive. Single‐dose irradiation with 15 Gy implicates a functional impairment of the lachrymal gland, which is associated with early immunohistological and ultrastructural alterations. These changes may represent objective surrogate parameters for radiogenic dysfunction and prerequisites for further investigations on radioprotection of lachrymal glands during radiotherapy of the periorbital region.
Patients’ perceptions of the concept of the quality of care in the psychiatric setting: a phenomenographic study
Authors: Schröder Agneta , Ahlström Gerd , Larsson Bodil Wilde 
Published: January 2006

Aim.  The aim was to describe how patients perceived the concept of quality of care in psychiatric care.Background.  It is important to include patients’ experiences in defining quality of care and in the development of instruments measuring quality of psychiatric care, as patients have unique information. But only a limited number of studies have directly involved patients.Design.  It was a qualitative interview study with 20 adult in and outpatients from psychiatric care.Method.  A phenomenographic approach was used for the analysis of the interviews.Results.  The results showed that quality of care was perceived as a positive concept, namely as ‘good’ quality of care. The normative component was striking. Five descriptive categories emerged: The patient's dignity is respected; The patient's sense of security with regard to care; The patient's participation in the care; The patient's recovery; and The patient's care environment. Two conceptions emerged that had not emerged explicitly in earlier studies of quality of care: Being helped to reduce the shame and Being looked upon as like anyone else.Conclusions.  The findings emphasize the importance of the interpersonal relationship between patients and staff. There is a need for further exploration of central aspects of quality in psychiatric care.Relevance to clinical practice.  It is important that the knowledge about how patients perceived the quality of care in psychiatric care is included in the planning and evaluation of care. The guidelines should designate quality of care from the patient perspective as the goal of interventions.
Consultation with children in hospital: children, parents’ and nurses’ perspectives
Authors: Coyne Imelda 
Published: January 2006

Aims and objectives.  To explore children's, parents’ and nurses’ views on participation in care in the healthcare setting.Background.  Children have a right to be consulted and involved in their care.Design.  The grounded theory method was used and data were collected through in‐depth interviews, questionnaires and observation. Sample consisted of 11 children, 10 parents and 12 nurses from four paediatric wards in two hospitals in England.Results.  Parents felt that children should be involved in the decision‐making process thereby enhancing and promoting children's self‐esteem and positive self‐regard, which would consequently enhance their overall welfare. Likewise, children expressed the need for consultation and information so that they could understand their illness; be involved in their care, and prepare themselves for procedures. However, children's own opinions and views were underused and they had varying experiences of being consulted about their care and treatment. Nurses appeared to hold varying and discrepant views on the involvement of children in decisions and for some nurses, the child's involvement seemed to be dependent on the child's cognitive maturity and being defined as a rational subject.Conclusion.  Health professionals’ communication behaviour may reflect recognition of children's cognitive abilities rather than their competence to understand. The fact that children's nurses appeared to make decisions about involving children in decision making in the absence of a reliable framework was a significant finding and highlights a real problem in the current climate.Relevance to clinical practice.  Nurses faced with workforce pressures may encounter considerable challenges to facilitating children's involvement in decisions about their care. Hence it is imperative that nurses’ examine the basis of their decisions and use more explicit criteria for determining children's involvement.
Development of a measure to assess the impact of epilepsy on people with an intellectual disability: the Glasgow Epilepsy Outcome Scale – Client version (GEOS‐C)
Authors: Watkins J. , Espie C. A. , Curtice L. , Mantala K. , Corp A. , Foley J. 
Published: January 2006

AbstractBackground  Epilepsy is common in people with intellectual disability, yet clinicians and researchers seldom obtain information directly from the client. The development and preliminary validation of a novel measure for use with people with mild to moderate intellectual disabilities is described.Methods  Focus group methods (6 groups; 24 participants) identified issues of concern, and qualitative analysis (NUD*IST) was applied to derive items and themes for a draft scale. Psychometric scale development techniques were then used in a pilot study and subsequent field‐testing to investigate validity and reliability (n = 46).Results  A total of 148 issues of concern was reduced initially to 52 and then to 42 items using these methods. The derived scale comprised sub‐scales reflecting (1) concerns about having seizures; (2) about injury; (3) about issues during; and (4) after seizures; (5) about medication; (6) about what people think; and (7) about daily life. Cronbach α for the Glasgow Epilepsy Outcome Scale – Client version (GEOS‐C) was 0.92, and ranged from 0.64–0.81 for the sub‐scales. Relatively weak associations (r ≤ 0.40), between client and family carer, staff carer or clinician views, suggests that proxy reports are not good predictors of how people with epilepsy themselves are feeling. Preliminary validation suggests that the GEOS‐C can discriminate on variables of clinical importance.Conclusions  The GEOS‐C complements existing GEOS measures, can be completed in 5–15 min depending upon the level of support required, and may provide a valuable clinical and research tool. Further validational work and appraisal of sensitivity are required.