bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Ryanodine Receptor–mediated Calcium Release in Human B Cells
Authors: McKinney Leslie C. , Butler Thomas , Mullen Shawn P. , Klein Michael G. 
Published: May 2006

Background
Mutations in the ryanodine type 1 receptor (RyR1) are causative for malignant hyperthermia. Studies in human B lymphocytes have shown that measurement of RyR1-mediated intracellular Ca(2+) (Ca(2+)(i)) release can differentiate between normal and malignant hyperthermia-susceptible individuals. The authors have further developed the B-cell assay by pharmacologically characterizing RyR1-mediated Ca release in two normal human B-cell lines and demonstrating increased sensitivity of lymphocytes to the RyR1 agonist 4-chloro-m-cresol (4-CmC) in the porcine model of MH.

Methods
Ca(2+)(i) was measured fluorometrically using fura-2 in populations of cells in suspension or with fluo-4 in single cells using confocal microscopy. The Dakiki and PP normal human B cell lines were used, as well as lymphocytes obtained from normal and malignant hyperthermia-susceptible pigs. 4-CmC was used to elicit RyR1-mediated Ca release; all experiments were performed in the absence of external Ca(2+).

Results
EC(50) values for 4-CmC were 0.98 and 1.04 mm for Dakiki and PP cells, respectively, demonstrating reproducibility. The 4-CmC-induced increase in Ca(2+)(i) was eliminated by thapsigargin and was unaffected by xestospongin C. The Ca(2+)(i) increase was separable from mitochondrial stores and was inhibited by azumolene. Caffeine did not induce Ca(2+)(i) release, but ryanodine depleted intracellular stores by 50%. Lymphocytes from pigs carrying the Arg614Cys mutation in RyR1 showed increased sensitivity to 4-CmC (EC(50) = 0.47 vs. 0.81 mm for cells derived from normal animals).

Conclusions
RyR1-mediated Ca(2+) signals can be pharmacologically distinguished from other intracellular sources in human B cells, and alterations of RyR1 function can be successfully detected using Ca(2+) release from intracellular stores as an end point.
Effect of the Physical Properties of Isoflurane, Sevoflurane, and Desflurane on Pulmonary Resistance in a Laboratory Lung Model
Authors: Nyktari Vasilia G. , Papaioannou Alexandra A. , Prinianakis George , Mamidakis Eytichis G. , Georgopoulos Dimitris , Askitopoulou Helen 
Published: May 2006

Background
Airway resistance depends not only on an airway's geometry but also on flow rate, and gas density and viscosity. A recent study showed that at clinically relevant concentrations, the mixtures of volatile agents with air and oxygen and oxygen-nitrogen affected the density of the mixture. The goal of the current study was to investigate the effect of different minimum alveolar concentrations (MACs) of three commonly used volatile agents, isoflurane, sevoflurane, and desflurane, on the measurements of airway resistance.

Methods
A two-chamber fixed-resistance test lung was connected to an anesthesia machine using the volume control mode of ventilation. Pulmonary resistance was calculated at baseline (25% oxygen in air); at 1.0, 1.5, and 2.0 MAC; and also at the same concentrations, 1.2% and 4%, of isoflurane, sevoflurane, and desflurane mixtures with 25% oxygen in air. The analysis of variance test for repeated measures and probabilities for post hoc Tukey and least significant difference tests were used.

Results
Isoflurane affected pulmonary resistance only at 2 MAC. Sevoflurane caused a significant increase of pulmonary resistance at 1.5 and 2 MAC, whereas desflurane caused the greatest increase in pulmonary resistance at all MAC values used. At 1.2% concentration, no difference from the baseline resistance was observed, whereas at 4%, the three agents produced similar increases of pulmonary resistance.

Conclusion
High concentrations of volatile agents in 25% oxygen in air increased the density of the gas mixture and the calculated resistance of a test lung model with fixed resistance.
The Antibiotic Erythromycin Induces Tolerance against Transient Global Cerebral Ischemia in Rats (Pharmacologic Preconditioning)
Authors: Brambrink Ansgar M. , Koerner Ines P. , Diehl Kathrin , Strobel Georg , Noppens Ruediger , Kempski Oliver 
Published: May 2006

Background
Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression.

Methods
Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later.

Results
Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged.

Conclusions
Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.
Mechanism-based Pharmacokinetic–Pharmacodynamic Modeling of the Antinociceptive Effect of Buprenorphine in Healthy Volunteers
Authors: Yassen Ashraf , Olofsen Erik , Romberg Raymonda , Sarton Elise , Danhof Meindert , Dahan Albert 
Published: May 2006

Background
The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers.

Methods
Data on the time course of the antinociceptive effect after intravenous administration of 0.05-0.6 mg/70 kg buprenorphine in healthy volunteers was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis.

Results
A three-compartment pharmacokinetic model best described the concentration time course. Four structurally different pharmacokinetic-pharmacodynamic models were evaluated for their appropriateness to describe the time course of buprenorphine's antinociceptive effect: (1) E(max) model with an effect compartment model, (2) "power" model with an effect compartment model, (3) receptor association-dissociation model with a linear transduction function, and (4) combined biophase equilibration/receptor association-dissociation model with a linear transduction function. The latter pharmacokinetic-pharmacodynamic model described the time course of effect best and was used to explain time dependencies in buprenorphine's pharmacodynamics. The model converged, yielding precise estimation of the parameters characterizing hysteresis and the relation between relative receptor occupancy and antinociceptive effect. The rate constant describing biophase equilibration (k(eo)) was 0.00447 min(-1) (95% confidence interval, 0.00299-0.00595 min(-1)). The receptor dissociation rate constant (k(off)) was 0.0785 min(-1) (95% confidence interval, 0.0352-0.122 min(-1)), and k(on) was 0.0631 ml . ng(-1) . min(-1) (95% confidence interval, 0.0390-0.0872 ml . ng(-1) . min(-1)).

Conclusion
This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect for antinociception.
Parturition in the Rat
Authors: Catheline Gwénaëlle , Touquet Bastien , Besson Jean-Marie , Lombard Marie-Christine 
Published: May 2006

Background
Pain during labor is a common and severe phenomenon, but its clinical management remains haphazard because its neurophysiology is poorly understood. In the current study, the authors evaluate the parturient rat as a relevant model to study the pharmacology of labor pain.

Methods
Control of birth timing in term pregnant rats was achieved by gavage with RU 486 (5 mg/kg) the day before the expected day of parturition. The behavioral events preceding the expulsion of the first pup were analyzed, and immunodetection of the c-Fos protein was used to evaluate the spinal neuronal activity at the lumbosacral level where genital and perineal inputs terminate.

Results
Hind limb and abdominal stretches occurred during labor (mean number, 57 +/- 10), arbitrarily defined as the time elapsed between the first stretch and the expulsion of the first pup (mean duration, 62 +/- 5 min). Subcutaneous oxytocin increased the frequency of stretches, accounting for the fact that these manifestations are linked to uterine contractions. Finally, epidural morphine (30 microg/10 microl) in oxytocin-treated rats, although resulting in no change of labor duration, significantly decreased the number of stretches (8 +/- 2 vs. 57 +/- 12 for epidural saline) and the number of c-Fos-positive neurons in the lumbosacral spinal segments (80 +/- 25 vs. 165 +/- 17 for epidural saline).

Conclusions
These results indicate that stretches during labor in the rat correspond to a behavioral response to nociception associated with uterine contractions and suggest that parturition in the rat could be a relevant model to investigate nociceptive mechanisms associated with parturition in women.
Differential Spinal Cord Gene Expression in Rodent Models of Radicular and Neuropathic Pain
Authors: LaCroix-Fralish Michael L. , Tawfik Vivianne L. , Tanga Flobert Y. , Spratt Kevin F. , DeLeo Joyce A. 
Published: May 2006

Background
Neuropathic pain and radicular low back pain both have a major impact on human health worldwide. Microarray gene analysis on central nervous system tissues holds great promise for discovering novel targets for persistent pain modulation.

Methods
Rat models of lumbar radiculopathy (L5 nerve root ligation) and neuropathy (L5 spinal nerve transection) were used for these studies. The authors measured mechanical allodynia followed by analysis of global gene expression in the lumbar spinal cord at two time points (7 days and 14 days) after surgery using the Affymetrix RAE230A GeneChip(R) (Santa Clara, CA). The expression patterns of several genes of interest were subsequently confirmed using real-time reverse transcriptase polymerase chain reaction.

Results
The authors observed similarly robust mechanical allodynia in both models. Second, they observed significant differences in lumbar spinal cord gene expression across chronic pain models. There was little overlap between genes altered in each injury model, suggesting that the site and type of injury produce distinct spinal mechanisms mediating the observed mechanical allodynia. The authors further confirmed a subset of the genes using reverse transcriptase polymerase chain reaction and identified several genes as either neuropathy-associated genes or radiculopathy-associated genes.

Conclusions
These two models of persistent pain produce similar allodynic outcomes but produce differential gene expression. These results suggest that diverging mechanisms lead to a common behavioral outcome in these pain models. Furthermore, these distinct pathophysiologic mechanisms in neuropathic versus radicular pain may implicate unique drug therapies for these types of chronic pain syndromes.
Why Do Women Go Along with This Stuff?
Authors: Kitzinger Sheila , Green Josephine M. , Chalmers Beverley , Keirse Marc J.N.C. , Lindstrom Kathleen , Hemminki Elina 
Published: May 2006

PREFACE:  Normal childbirth has become jeopardized by inexorably rising interventions around the world. In many countries and settings, cesarean surgery, labor induction, and epidural analgesia continue to increase beyond all precedent, and without convincing evidence that these actions result in improved outcomes (1,2). Use of electronic fetal monitoring is endemic, despite evidence of its ineffectiveness and consequences for most parturients (1,3); ultrasound examinations are too often done unnecessarily, redundantly, or for frivolous rather than indicated reasons (4); episiotomies are still routine in many settings despite clear evidence that this surgery results in more harm than good (5); and medical procedures, unphysiological positions, pubic shaving and enemas, intravenous lines, enforced fasting, drugs, and early mother‐infant separation are used unnecessarily (1). Clinicians write and talk about the ideal of evidence‐based obstetrics, but do not practice it consistently, if at all. Why do women go along with this stuff? In this Roundtable Discussion, Part 1, we asked some maternity care professionals and advocates to discuss this question. (BIRTH 33:2 June 2006)
Bonfils semirigid endoscope for guidance during percutaneous tracheostomy
Authors: Buehner U. , Oram J. , Elliot S. , Mallick A. , Bodenham A. 
Published: May 2006

SummaryWe report on the use of the Bonfils semirigid scope for endoscopic guidance during percutaneous dilational tracheostomy. Forty patients requiring percutaneous dilational tracheostomy on the General or Neurosurgical Intensive Care Unit were enrolled in this study. We used the ‘45 degree curved distal tip’ scope in the first 15 patients, evaluating its ease of use, optical quality of focus and image resolution as well as light intensity on a 10‐point scale. We evaluated straight and curved versions of it in another 15 and 10 patients, respectively. We examined the impact on ventilation and cardiovascular parameters. In all patients (n = 40) visualisation of the procedure was satisfactory. There were no clinically significant changes in ventilatory or cardiovascular parameters. The image quality for most patients received a score of 7–10. The Bonfils scope provides a practical alternative to flexible bronchoscopes in this setting.
Learning and performance of tracheal intubation by novice personnel: a comparison of the Airtraq® and Macintosh laryngoscope
Authors: Maharaj C. H. , Costello J. F. , Higgins B. D. , Harte B. H. , Laffey J. G. 
Published: May 2006

SummaryDirect laryngoscopic tracheal intubation is taught to many healthcare professionals as it is a potentially lifesaving procedure. However, it is a difficult skill to acquire and maintain, and, of concern, the consequences of poorly performed intubation attempts are potentially serious. The Airtraq® Laryngoscope is a novel intubation device which may possess advantages over conventional direct laryngoscopes for use by novice personnel. We conducted a prospective trial with 40 medical students who had no prior airway management experience. Following brief didactic instruction, each participant took turns in performing laryngoscopy and intubation using the Macintosh and Airtraq devices under direct supervision. Each student was allowed up to three attempts to intubate in three laryngoscopy scenarios using a Laerdal® Intubation Trainer and one scenario in a Laerdal® SimMan® Manikin. They then performed tracheal intubation of the normal airway a second time to characterise the learning curve for each device. The Airtraq provided superior intubating conditions, resulting in greater success of intubation, particularly in the difficult laryngoscopy scenarios. In both easy and simulated difficult laryngoscopy scenarios, the Airtraq decreased the duration of intubation attempts, reduced the number of optimisation manoeuvres required, and reduced the potential for dental trauma. The Airtraq device showed a rapid learning curve and the students found it significantly easier to use. The Airtraq appears to be a superior device for novice personnel to acquire the skills of tracheal intubation.
The status of new anticoagulants
Authors: Bates Shannon M. , Weitz Jeffrey I. 
Published: May 2006

SummaryCurrently available anticoagulants include heparin, low‐molecular weight heparin, fondaparinux and warfarin. Despite advances with low‐molecular weight heparin and fondaparinux, the currently available agents have limitations that have provided the impetus for the development of new drugs for prevention and treatment of both venous and arterial thromboembolism. Novel anticoagulants targeting specific steps in coagulation are in various stages of development. This paper reviews the pharmacology of these new agents and describes the results of clinical trials with new anticoagulants in more advanced stages of clinical testing.
Evidence for a lacustrine faunal refuge in the Larsemann Hills, East Antarctica, during the Last Glacial Maximum
Authors: Cromer Louise , Gibson John A. E. , Swadling Kerrie M. , Hodgson Dominic A. 
Published: May 2006

AbstractAim  There is no previous direct evidence for the occurrence of lacustrine refuges for invertebrate fauna in Antarctica spanning the Last Glacial Maximum (LGM). In the absence of verified LGM lacustrine refuges many species are believed to result from Holocene dispersal from sub‐Antarctic islands and continents further north. If freshwater lake environments were present throughout the LGM, extant freshwater species may have been associated with Antarctica prior to this glacial period. This study looked at faunal microfossils in a sediment core from an Antarctic freshwater lake. This lake is unusual in that, unlike most Antarctic lakes, the sediment record extends to c. 130,000 yr bp, i.e. prior to the LGM.Location  Lake Reid, Larsemann Hills, East Antarctica (76°23′ E; 69°23′ S).Methods  Palaeofaunal communities in Lake Reid were identified through examination of faunal microfossils in a sediment core that extended to c. 130,000 yr bp.Results  Ephippia and mandibles from the cladoceran Daphniopsis studeri and loricae of the rotifer Notholca sp. were found at all depths in the sediment, indicating that these two species have been present in the lake for up to 130,000 years. Copepod mandibles were also present in the older section of the core, yet were absent from the most recent sediments, indicating extinction of this species from Lake Reid during the LGM.Main conclusion  The presence of D. studeri and Notholca sp. microfossils throughout the entire Lake Reid core is the first direct evidence of a glacial lacustrine refugium for invertebrate animals in Antarctica, and indicates the presence of a relict fauna on the Antarctic continent.
Anagenetic evolution in island plants
Authors: Stuessy Tod F. , Jakubowsky Gerhard , Gómez Roberto Salguero , Pfosser Martin , Schlüter Philipp M. , Fer Tomas , Sun Byung‐Yun , Kato Hidetoshi 
Published: May 2006

AbstractAim Plants in islands have often evolved through adaptive radiation, providing the classical model of evolution of closely related species each with strikingly different morphological and ecological features and with low levels of genetic divergence. We emphasize the importance of an alternative (anagenetic) model of evolution, whereby a single island endemic evolves from a progenitor and slowly builds up genetic variation through time.Location Continental and oceanic islands.Methods We surveyed 2640 endemic angiosperm species in 13 island systems of the world, both oceanic and continental, for anagenetic and cladogenetic patterns of speciation. Genetic data were evaluated from a progenitor and derivative species pair in Ullung Island, Korea, and Japan.Results We show that the anagenetic model of evolution is much more important in oceanic islands than previously believed, accounting for levels of endemic specific diversity from 7% in the Hawaiian Islands to 88% in Ullung Island, Korea, with a mean for all islands of 25%. Examination of an anagenetically derived endemic species in Ullung Island reveals genetic (amplified fragment length polymorphism) variation equal or nearly equal to that of its continental progenitor.Main conclusions We hypothesize that, during anagenetic speciation, initial founder populations proliferate, and then accumulate genetic variation slowly through time by mutation and recombination in a relatively uniform environment, with drift and/or selection yielding genetic and morphological divergence sufficient for the recognition of new species. Low‐elevation islands with low habitat heterogeneity are highly correlated with high levels of anagenetic evolution, allowing prediction of levels of the two models of evolution from these data alone. Both anagenetic and adaptive radiation models of speciation are needed to explain the observed levels of specific and genetic diversity in oceanic islands.
YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli
Authors: Malinverni Juliana C. , Werner John , Kim Seokhee , Sklar Joseph G. , Kahne Daniel , Misra Rajeev , Silhavy Thomas J. 
Published: May 2006

SummaryRecent advances in the study of bacterial membranes have led to the identification of a multicomponent YaeT complex in the outer membrane (OM) of Gram‐negative bacteria that is involved in the targeting and folding of β‐barrel outer membrane proteins (OMPs). In Escherichia coli, this complex consists of an essential OMP, YaeT, and three OM lipoproteins, YfgL, NlpB and YfiO. YfiO is the only essential lipoprotein component of the complex. We show that this lipoprotein is required for the proper assembly and/or targeting of OMPs to the OM but not the assembly of lipopolysaccharides (LPS). Depletion of YfiO causes similar phenotypes as does the depletion of YaeT, and we conclude that YfiO plays a critical role in YaeT‐mediated OMP folding. We demonstrate that YfiO and YfgL directly interact with YaeT in vitro, while NlpB interacts directly with YfiO. Genetic analysis verifies the importance of YfiO and its interactions with NlpB in maintaining the functional integrity of the YaeT complex.
O3impacts on plant development: a meta‐analysis of root/shoot allocation and growth
Authors: GRANTZ D. A. , GUNN S. , VU H.‐B. 
Published: May 2006

ABSTRACTThe mechanism of O3action on plants remains poorly characterized. Symptoms include visible lesions on the leaf surface, reduced growth and a hypothesized reduction in allocation of carbohydrate to roots. The generality of this latter phenomenon has not been demonstrated. Here, a meta‐analysis is performed of all available experimental data, to test the hypotheses that O3exposure of the shoot inhibits biomass allocation below ground (the root/shoot allometric coefficient,k) and inhibits whole‐plant growth rate [relative growth rate (RGR)]. Bothkand RGR were significantly reduced by O3(5.6 and 8.2%, respectively). Variability inkwas greater than in RGR, and both exhibited some positive as well as mostly negative responses. The effects onkwere distinct from the effects on RGR. In some cases,kwas reduced while RGR was unaffected. Slow‐growing plants (small RGR) exhibited the largest declines ink. These observations may have mechanistic implications regarding O3phytotoxicity. There were no effects of type of exposure chamber on sensitivity to O3. The analyses indicate that the O3inhibition of allocation to roots is real and general, but variable. Further experiments are needed for under‐represented plant groups, to characterize exceptions to this generalization and to evaluate O3–environment interactions.