bluuebunny/crossref_metadata_2025 huggingface dataset:
Azithromycin has an antiproliferative and autophagic effect on airway smooth muscle cells
Authors: Stamatiou R. , Paraskeva E. , Boukas K. , Gourgoulianis K. I. , Molyvdas P-A. , Hatziefthimiou A. A.
Published: April 2009

Azithromycin is used in long-term, low-dose treatment of airway diseases where airway wall remodelling is present. Since it improves total score symptom and respiratory function of such patients, we hypothesise that azithromycin's additional clinical benefits are due to an inhibition of airway smooth muscle cell (SMC) proliferation.

Rabbit tracheal SMCs were treated with azithromycin (10−5to 10−6 M) in the presence or absence of 10% fetal bovine serum (FBS). The proliferation was estimated using the Cell Titer 96® AQueousOne Solution Assay (Promega, Madison, WI, USA). Cell viability was assessed with Trypan blue staining and flow cytometry after 7-aminoactinomycin D (7-AAD) staining. Induction of autophagy was studied by indirect immmunofluorescence and/or Western blotting with antibodies against human smooth muscle α-actin, beclin 1, light chain 3 and caspase 3. The involvement of the phosphoinositide 3-kinase pathway was investigated with the inhibitors LY294002 and wortmannin.

Incubation with azithromycin for 72 h in the presence of FBS reduced SMC proliferation and viability in a dose-dependent manner. Azithromycin treatment was accompanied by the formation of cytoplasmic vacuoles, characteristic of autophagy. All these effects were reversible after azithromycin removal and prevented by the autophagy inhibitor, 3-methyladenine, or LY294002, but not by wortmannin.

In conclusion, azithromycin reduces proliferation and causes autophagy of airway SMCs.
Propofolversuscombined sedation in flexible bronchoscopy: a randomised non-inferiority trial
Authors: Stolz D. , Kurer G. , Meyer A. , Chhajed P. N. , Pflimlin E. , Strobel W. , Tamm M.
Published: April 2009

Combined sedation with a benzodiazepine and an opiate has been proposed as standard sedation for bronchoscopy. Propofol is a sedative–hypnotic with a rapid onset of action and fast recovery time, but carries the potential risk of respiratory failure.

Consecutive patients (n = 200) were randomly allocated to receive either the combination midazolam and hydrocodone or intravenous propofol. The primary end-points were the mean lowest arterial oxygen saturation during bronchoscopy and the readiness-for-discharge score 1 h after the procedure.

The mean lowest arterial oxygen saturation during bronchoscopy did not differ across treatment groups (p = 0.422), and the number of patients recording an arterial oxygen saturation of ≤90% on at least one occasion was similar in both groups (p = 0.273). The median (interquartile range) readiness-for-discharge score 1 h after the procedure was significantly higher in the propofol group than in the combined sedation group (8 (6–9)versus7 (5–9); p = 0.035). Patients assigned propofol exhibited less tachycardia during bronchoscopy and for ≥1 h after the examination. Minor procedural complications were noted in 71 (35.5%) patients and exhibited a similar incidence in both treatment arms (p = 0.460).

Propofol is as effective and safe as combined sedation in patients undergoing flexible bronchoscopy, thus representing an appealing option if timely discharge is a priority.
Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD
Authors: Miravitlles M. , Marín A. , Monsó E. , Vilà S. , de la Roza C. , Hervás R. , Esquinas C. , García M. , Millares L. , Morera J. , Torres A.
Published: April 2009

This study was designed to investigate the efficacy of moxifloxacin for the eradication of bacterial colonisation of the airways in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Out of 119 stable patients with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50% predicted) were colonised with potentially pathogenic microorganisms (PPMs) and were included in a randomised, double-blind, placebo-controlled trial with moxifloxacin 400 mg daily for 5 days.

Eradication rates were 75% with moxifloxacin and 30% with placebo at 2 weeks (p = 0.01). Bacterial persistence at 8 weeks was still higher (not significantly) in the placebo arm (five (25%) out of 20versusone (5%) out of 20; p = 0.18). The frequencies of acquisition of a new PPM were high and similar in both treatment groups; consequently, the prevalence of colonisation at 8 weeks was also similar between treatment arms. No difference was found in the number of patients with exacerbations during the 5-month follow-up. Only the acquisition of a new PPM during follow-up showed a statistically significant relationship with occurrence of an exacerbation.

Moxifloxacin was effective in eradicating PPMs in patients with positive sputum cultures. However, most patients were recolonised after 8 weeks of follow-up. Acquisition of a new strain of bacteria was associated with an increased risk of developing an exacerbation.
Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function
Authors: Moroz Olga V , Burkitt Will , Wittkowski Helmut , He Wei , Ianoul Anatoli , Novitskaya Vera , Xie Jingjing , Polyakova Oxana , Lednev Igor K , Shekhtman Alexander , Derrick Peter J , Bjoerk Per , Foell Dirk , Bronstein Igor B
Published: April 2009

Background

Human S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. S100A12 is an important factor in host/parasite defenses and in the inflammatory response. Like several other S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of zinc regulation have been proposed for a number of S100 proteins e.g. S100B, S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is strongly dependent on cellular microenvironment.

Results

The aim of the study was to explore the factors that influence S100A12 oligomerization and target interaction. A comprehensive series of biochemical and biophysical experiments indicated that changes in the concentration of calcium and zinc led to changes in the oligomeric state of S100A12. Surface plasmon resonance confirmed that the presence of both calcium and zinc is essential for the interaction of S100A12 with one of its extracellular targets, RAGE – the Receptor for Advanced Glycation End products. By using a single-molecule approach we have shown that the presence of zinc in tissue culture medium favors both the oligomerization of exogenous S100A12 protein and its interaction with targets on the cell surface.

Conclusion

We have shown that oligomerization and target recognition by S100A12 is regulated by both zinc and calcium. Our present work highlighted the potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling.
Genome-wide QTL mapping for three traits related to teat number in a White Duroc × Erhualian pig resource population
Authors: Ding Nengshui , Guo Yuanmei , Knorr Christoph , Ma Junwu , Mao Huirong , Lan Lütao , Xiao Shijun , Ai Huashui , Haley Chris S , Brenig Bertram , Huang Lusheng
Published: April 2009

Background

Teat number is an important fertility trait for pig production, reflecting the mothering ability of sows. It is also a discrete and often canalized trait presenting bilateral symmetry with minor differences between the two sides, providing a potential power to evaluate fluctuating asymmetry and developmental instability. The knowledge of its genetic control is still limited. In this study, a genome-wide scan was performed with 183 microsatellites covering the pig genome to identify quantitative trait loci (QTL) for three traits related to teat number including the total teat number (TTN), the teat number at the left (LTN) and right (RTN) sides in a large scale White Duroc × Erhualian resource population.

Results

A sex-average linkage map with a total length of 2350.3 cM and an average marker interval of 12.84 cM was constructed. Eleven genome-wide significant QTL for TTN were detected on 8 autosomes including pig chromosomes (SSC) 1, 3, 4, 5, 6, 7, 8 and 12. Six suggestive QTL for this trait were detected on SSC6, 9, 13, 14 and 16. Eight chromosomal regions each on SSC1, 3, 4, 5, 6, 7, 8 and 12 showed significant associations with LTN. These regions were also evidenced as significant QTL for RTN except for those on SSC6 and SSC8. The most significant QTL for the 3 traits were all located on SSC7. Erhualian alleles at most of the identified QTL had positive additive effects except for three QTL on SSC1 and SSC7, at which White Duroc alleles increased teat numbers. On SSC1, 6, 9, 13 and 16, significant dominance effects were observed on TTN, and predominant imprinting effect on TTN was only detected on SSC12.

Conclusion

The results not only confirmed the QTL regions from previous experiments, but also identified five new QTL for the total teat number in swine. Minor differences between the QTL regions responsible for LTN and RTN were validated. Further fine mapping should be focused on consistently identified regions with small confidence intervals, such as those on SSC1, SSC7 and SSC12.
Cervical cancer isolate PT3, super-permissive for adeno-associated virus replication, over-expresses DNA polymerase δ, PCNA, RFC and RPA
Authors: Kang Bum Yong , You Hong , Bandyopadhyay Sarmistha , Agrawal Nalini , Melchert Russell B , Basnakian Alexei G , Liu Yong , Hermonat Paul L
Published: April 2009

Background

Adeno-associated virus (AAV) type 2 is an important virus due to its use as a safe and effective human gene therapy vector and its negative association with certain malignancies. AAV, a dependo-parvovirus, autonomously replicates in stratified squamous epithelium. Such tissue occurs in the nasopharynx and anogenitals, from which AAV has been clinically isolated. Related autonomous parvoviruses also demonstrate cell tropism and preferentially replicate in oncogenically transformed cells. Combining these two attributes of parvovirus tropism, squamous and malignant, we assayed if AAV might replicate in squamous cervical carcinoma cell isolates.

Results

Three primary isolates (PT1-3) and two established cervical cancer cell lines were compared to normal keratinocytes (NK) for their ability to replicate AAV. One isolate, PT3, allowed for high levels of AAV DNA replication and virion production compared to others. In research by others, four cellular components are known required for in vitro AAV DNA replication: replication protein A (RPA), replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase delta (POLD1). Thus, we examined PT3 cells for expression of these components by DNA microarray and real-time quantitative PCR. All four components were over-expressed in PT3 over two representative low-permissive cell isolates (NK and PT1). However, this super-permissiveness did not result in PT3 cell death by AAV infection.

Conclusion

These data, for the first time, provide evidence that these four cellular components are likely important for AAV in vivo DNA replication as well as in vitro. These data also suggest that PT3 will be a useful reagent for investigating the AAV-permissive transcriptome and AAV anti-cancer effect.
The zinc finger protein Zn72D and DEAD box helicase Belle interact and control maleless mRNA and protein levels
Authors: Worringer Kathleen A , Chu Feixia , Panning Barbara
Published: April 2009

Background

The Male Specific Lethal (MSL) complex is enriched on the single X chromosome in maleDrosophilacells and functions to upregulate X-linked gene expression and equalize X-linked gene dosage with XX females. The zinc finger protein Zn72D is required for productive splicing of themaleless(mle) transcript, which encodes an essential subunit of the MSL complex. In the absence of Zn72D, MLE levels are decreased, and as a result, the MSL complex no longer localizes to the X chromosome and dosage compensation is disrupted. To understand the molecular basis of Zn72D function, we identified proteins that interact with Zn72D.

Results

Among several proteins that associate with Zn72D, we found the DEAD box helicase Belle (Bel). Simultaneous knockdown ofZn72Dandbelrestored MSL complex localization to the X chromosome and dosage compensation. MLE protein was restored to 70% of wild-type levels, although the level of productively splicedmletranscript was still four-fold lower than in wild-type cells. The increase in production of MLE protein relative to the amount of correctly splicedmlemRNA could not be attributed to an alteration in MLE stability.

Conclusion

These data indicate that Zn72D and Bel work together to controlmlesplicing and protein levels. Thus Zn72D and Bel may be factors that coordinate splicing and translational regulation.
Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)
Authors: Lüblinghoff Nicola , Winkler Karl , Winkelmann Bernhard R , Seelhorst Ursula , Wellnitz Britta , Boehm Bernhard O , März Winfried , Hoffmann Michael M
Published: April 2009

Background

Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography.

Methods

We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP.

Results

In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI.

Conclusion

Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI.
Early markers of airways inflammation and occupational asthma: Rationale, study design and follow-up rates among bakery, pastry and hairdressing apprentices
Authors: Tossa Paul , Bohadana Abraham , Demange Valérie , Wild Pascal , Michaely Jean-Pierre , Hannhart Bernard , Paris Christophe , Zmirou-Navier Denis
Published: April 2009

Background

Occupational asthma is a common type of asthma caused by a specific agent in the workplace. The basic alteration of occupational asthma is airways inflammation. Although most patients with occupational asthma are mature adults, there is evidence that airways inflammation starts soon after inception of exposure, including during apprenticeship. Airways hyper responsiveness to methacholine is a valid surrogate marker of airways inflammation, which has proved useful in occupational epidemiology. But it is time-consuming, requires active subject's cooperation and is not readily feasible. Other non-invasive and potentially more useful tests include the forced oscillation technique, measurement of fraction exhaled nitric oxide, and eosinophils count in nasal lavage fluid.

Methods and design

This study aims to investigate early development of airways inflammation and asthma-like symptoms in apprentice bakers, pastry-makers and hairdressers, three populations at risk of occupational asthma whose work-related exposures involve agents of different nature. The objectives are to (i) examine the performance of the non-invasive tests cited above in detecting early airways inflammation that might eventually develop into occupational asthma; and (ii) evaluate whether, and how, constitutional (e.g. atopy) and behavioural (e.g. smoking) risk factors for occupational asthma modulate the effects of allergenic and/or irritative substances involved in these occupations. This paper presents the study rationale and detailed protocol.

Discussion

Among 441 volunteers included at the first visit, 354 attended the fourth one. Drop outs were investigated and showed unrelated to the study outcome. Sample size and follow-up participation rates suggest that the data collected in this study will allow it to meet its objectives.
Acetylation of PAMAM dendrimers for cellular delivery of siRNA
Authors: Waite Carolyn L , Sparks Sarah M , Uhrich Kathryn E , Roth Charles M
Published: April 2009

Background

The advancement of gene silencing via RNA interference is limited by the lack of effective short interfering RNA (siRNA) delivery vectors. Rational design of polymeric carriers has been complicated by the fact that most chemical modifications affect multiple aspects of the delivery process. In this work, the extent of primary amine acetylation of generation 5 poly(amidoamine) (PAMAM) dendrimers was studied as a modification for the delivery of siRNA to U87 malignant glioma cells.

Results

PAMAM dendrimers were reacted with acetic anhydride to obtain controlled extents of primary amine acetylation. Acetylated dendrimers were complexed with siRNA, and physical properties of the complexes were studied. Dendrimers with up to 60% of primary amines acetylated formed ~200 nm complexes with siRNA. Increasing amine acetylation resulted in reduced polymer cytotoxicity to U87 cells, as well as enhanced dissociation of dendrimer/siRNA complexes. Acetylation of dendrimers reduced the cellular delivery of siRNA which correlated with a reduction in the buffering capacity of dendrimers upon amine acetylation. Confocal microscopy confirmed that escape from endosomes is a major barrier to siRNA delivery in this system.

Conclusion

Primary amine acetylation of PAMAM dendrimers reduced their cytotoxicity to U87 cells, and promoted the release of siRNA from dendrimer/siRNA complexes. A modest fraction (approximately 20%) of primary amines of PAMAM can be modified while maintaining the siRNA delivery efficiency of unmodified PAMAM, but higher degrees of amine neutralization reduced the gene silencing efficiency of PAMAM/siRNA delivery vectors.
Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis
Authors: Vesterdal Lise K , Folkmann Janne K , Jacobsen Nicklas R , Sheykhzade Majid , Wallin Håkan , Loft Steffen , Møller Peter
Published: April 2009

Background

Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines.

Methods

We investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/-) with different degree of atherosclerosis.

Results

The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice.

Conclusion

Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.
Clinical factors associated with a conservative gait pattern in older male veterans with diabetes
Authors: Wrobel James S , Crews Ryan T , Connolly John E
Published: April 2009

Background

Patients with diabetes and peripheral neuropathy are at higher risk for falls. People with diabetes sometimes adopt a more conservative gait pattern with decreased walking speed, widened base, and increased double support time. The purpose of this study was to use a multivariate approach to describe this conservative gait pattern.

Methods

Male veterans (mean age = 67 years; SD = 9.8; range 37–86) with diabetes (n = 152) participated in this study from July 2000 to May 2001 at the Veterans Affairs Medical Center, White River Junction, VT. Various demographic, clinical, static mobility, and plantar pressure measures were collected. Conservative gait pattern was defined by visual gait analysis as failure to demonstrate a heel‐to‐toe gait during the propulsive phase of gait.

Results

Patients with the conservative gait pattern had lower walking speed and decreased stride length compared to normal gait. (0.68 m/s v. 0.91 m/s, p < 0.001; 1.04 m v. 1.24 m, p < 0.001) Age, monofilament insensitivity, and Romberg's sign were significantly higher; and ankle dorsiflexion was significantly lower in the conservative gait pattern group. In the multivariate analysis, walking speed, age, ankle dorsiflexion, and callus were retained in the final model describing 36% of the variance. With the inclusion of ankle dorsiflexion in the model, monofilament insensitivity was no longer an independent predictor.

Conclusion

Our multivariate investigation of conservative gait in diabetes patients suggests that walking speed, advanced age, limited ankle dorsiflexion, and callus describe this condition more so than clinical measures of neuropathy.
Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis
Authors: Badot Valérie , Galant Christine , Nzeusseu Toukap Adrien , Theate Ivan , Maudoux Anne-Lise , Van den Eynde Benoît J , Durez Patrick , Houssiau Frédéric A , Lauwerys Bernard R
Published: April 2009

Introduction

To identify markers and mechanisms of resistance to adalimumab therapy, we studied global gene expression profiles in synovial tissue specimens obtained from severe rheumatoid arthritis (RA) patients before and after initiation of treatment.

Methods

Paired synovial biopsies were obtained from the affected knee of 25 DMARD (disease-modifying antirheumatic drug)-resistant RA patients at baseline (T0) and 12 weeks (T12) after initiation of adalimumab therapy. DAS28-CRP (disease activity score using 28 joint counts-C-reactive protein) scores were computed at the same time points, and patients were categorized as good, moderate, or poor responders according to European League Against Rheumatism criteria. Global gene expression profiles were performed in a subset of patients by means of GeneChip Human Genome U133 Plus 2.0 Arrays, and confirmatory immunohistochemistry experiments were performed on the entire cohort.

Results

Gene expression studies performed at baseline identified 439 genes associated with poor response to therapy. The majority (n = 411) of these genes were upregulated in poor responders and clustered into two specific pathways: cell division and regulation of immune responses (in particular, cytokines, chemokines, and their receptors). Immunohistochemistry experiments confirmed that high baseline synovial expression of interleukin-7 receptor α chain (IL-7R), chemokine (C-X-C motif) ligand 11 (CXCL11), IL-18, IL-18 receptor accessory (IL-18rap), and MKI67 is associated with poor response to adalimumab therapy. In vitro experiments indicated that genes overexpressed in poor responders could be induced in fibroblast-like synoviocytes (FLS) cultures by the addition of tumor necrosis factor-alpha (TNF-α) alone, IL-1β alone, the combination of TNF-α and IL-17, and the combination of TNF-α and IL-1β.

Conclusions

Gene expression studies of the RA synovium may be useful in the identification of early markers of response to TNF blockade. Genes significantly overexpressed at baseline in poor responders are induced by several cytokines in FLSs, thereby suggesting a role for these cytokines in the resistance to TNF blockade in RA.
Gravity characterization of the La Rioja Valley Basin, Argentina
Authors: Gimenez Mario Ernesto , Martinez Myriam Patricia , Jordan Teresa , Ruíz F. , Lince Klinger Federico
Published: April 2009

The La Rioja Valley is a sedimentary basin in the Pampean Ranges, a region of basement uplifts and broad valleys in the Andean foreland. The present study advances understanding of the genesis of the basin by providing subsurface data on its geometry and characteristics. Gravity and topographic data, including a newly completed gravity survey, were integrated to create a complete Bouguer anomaly map. Euler and Werner deconvolution techniques sum with traditional potential-fields methods and sparse independent data from seismic and magnetotelluric methods to test and constrain the subsurface geophysical characterization of the La Rioja Valley Basin. The residual anomaly, obtained through upward continuation, was inverted to obtain the best 3D gravity model of the La Rioja Valley Basin, which shows the first-order geometry of the basin. This reveals that the basin is asymmetric, with up to [Formula: see text] of low-density basin fill in a depocenter located in the west-central sector of the valley. Second-order features of the basin include a southeast-trending basement high, likely a fault zone that subdivides the basin, which has been revealed by a suite of analytical methods (3D model of depth to basement, a 2D inverse model, and Werner deconvolution solutions).
Gravitational and magnetic anomaly inversion using a tree-based geometry representation
Authors: Wildman Raymond A. , Gazonas George A.
Published: April 2009

Gravitational and magnetic anomaly inversion of homogeneous 2D and 3D structures is treated using a geometric parameterization that can represent multiple, arbitrary polygons or polyhedra and a local-optimization scheme based on a hill-climbing method. This geometry representation uses a tree data structure, which defines a set of Boolean operations performed on convex polygons. A variable-length list of points, whose convex hull defines a convex polygon operand, resides in each leaf node of the tree. The overall optimization algorithm proceeds in two steps. Step one optimizes geometric transformations performed on different convex polygons. This step provides approximate size and location data. The second step optimizes the points located on all convex hulls simultaneously, giving a more accurate representation of the geometry. Though not an inherent restriction, only the geometry is optimized, not including material values such as density or susceptibility. Results based on synthetic and measured data show that the method accurately reconstructs various structures from gravity and magnetic anomaly data. In addition to purely homogeneous structures, a parabolic density distribution is inverted for 2D inversion.
Decomposed element-free Galerkin method compared with finite-difference method for elastic wave propagation
Authors: Katou Masafumi , Matsuoka Toshifumi , Mikada Hitoshi , Sanada Yoshinori , Ashida Yuzuru
Published: April 2009

The decomposed element-free Galerkin (DEFG) method is a modified scheme to resolve shortcomings of memory use in element-free Galerkin (EFG) methods. DEFG solves elastic wave equation problems by alternately updating the stress-strain relations and the equations of motion as in the staggered-grid finite-difference (FD) method. DEFG requires at most twice the memory space, a size comparable to that used by the FD method. In addition, DEFG can adopt perfectly matched layer (PML) absorbing boundary conditions as in the FD case. To confirm that DEFG performs as well as FD, a 2D DEFG under PML boundary conditions was compared with an FD with fourth-order spatial accuracy (FD4) using an exact analytical solution of PS reflection waves. The DEFG results are as accurate as those obtained by FD4. In a comparison using Lamb’s problem with eight nodal spaces for the shortest S-wavelength, DEFG provides a remarkably accurate Rayleigh waveform over a distance of at least 50 wavelengths compared with 10 wavelengths for FD4. In the Rayleigh-wave case, DEFG with [Formula: see text] grid spacing is more accurate than FD4 with [Formula: see text] grid spacing, and DEFG uses less CPU time. DEFG may be a suitable method for numerical simulations of elastic wavefields, especially where a free surface is considered.
Characterization of bimodal facies distributions using effective anisotropic complex resistivity: A 2D numerical study based on Cole-Cole models
Authors: Winchen Tobias , Kemna Andreas , Vereecken Harry , Huisman Johan A.
Published: April 2009

Subsurface heterogeneity characteristics are of major importance in hydrologic modeling, and likely result in anisotropic electrical properties. We computed the anisotropic effective complex resistivity of 2D bimodal facies distributions numerically. Complex resistivities of individual facies are described in terms of the Cole-Cole relaxation model. First, we determined that effective DC resistivities of the distributions can be reasonably well described by power averaging the properties of individual facies. We found a clear relationship between the mixing parameter and correlation lengths of the facies distributions with respect to horizontal and vertical directions. Then, we used the power-law mixing model to invert for individual Cole-Cole model parameters by fitting predicted electrical responses to simulated spectral effective complex-resistivity data for the two perpendicular directions. Thus, it is possible to derive the electrical properties of individual facies as well as structural parameters describing bimodal facies distribution by means of a noninvasive measurement approach. In particular, anisotropy of the spectral complex-resistivity response provides information on correlation lengths of the distribution. This finding is relevant for all applications of electrical-impedance spectroscopy where anisotropy might be encountered.
A monoclonal protein identified by an anomalous lipaemia index
Authors: Monk Christopher , Wallage Michael , Wassell Julie , Whiteway Alastair , James Jacqueline , Beetham Robert
Published: April 2009

We describe a patient being investigated for anaemia where the lipaemia index on a Beckman Coulter DxC800 analyser was markedly elevated and out of keeping with the visual appearance of the serum. Subsequent investigation revealed a monoclonal IgM kappa immunoglobulin with type I cryoglobulin behaviour. The patient was then diagnosed with a non-Hodgkin B-cell lymphoma. We later identified a second patient with a similar anomalous index with an IgM lambda paraprotein, and a known marginal zone splenic lymphoma but were unable to confirm cryoglobulin behaviour prior to treatment. A review of 50 consecutive IgM paraproteins revealed no other anomalous lipaemia indices. We postulate that it is the properties of the paraprotein that determine its cryoglobulin behaviour that also render it susceptible to precipitation in the index diluent, not the fact of it being an IgM paraprotein per se. This appears to be the first reported case of a paraprotein identified following an anomalous lipaemia index.
A prospective study of causes of haemolysis during venepuncture: tourniquet time should be kept to a minimum
Authors: Saleem S , Mani V , Chadwick M A , Creanor S , Ayling R M
Published: April 2009

Background

Haemolysis is defined as the release of cellular components of erythrocytes and other blood cells into the extracellular space of blood. These cellular components can cause interference in laboratory measurements, potassium being a commonly measured analyte to be affected. A number of factors have been implicated in the aetiology of haemolysis. We undertook this study to enable us to identify and hence rectify causes of haemolysis in samples from patients on acute medical and surgical wards.

Methods

We performed a prospective study of 353 blood sampling events during February and March 2007. A proforma was used to obtain detailed information of each blood-taking episode. Information from the proforma was linked to the incidence of haemolysis obtained from the hospital computer system.

Results

The incidence of haemolysis among the samples studied was 6.5%. While staff group, method of sampling, tourniquet time and number of attempts at venepuncture were each univariately associated with haemolysis, stepwise logistic regression resulted in a final model which only included tourniquet time (odds ratio for haemolysis if tourniquet time >1 min was 19.5 [95% confidence interval [CI] 5.6–67.4%]).

Conclusion

Tourniquet time of more than a minute is associated with a significant increase in risk of haemolysis. Advice on tourniquet time is included in phlebotomy training within the hospital; hence a campaign of appropriately channelled continuing education on this issue may be successful in reducing the haemolysis rate.
A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease
Authors: Verwey N A , van der Flier W M , Blennow K , Clark C , Sokolow S , De Deyn P P , Galasko D , Hampel H , Hartmann T , Kapaki E , Lannfelt L , Mehta P D , Parnetti L , Petzold A , Pirttila T , Saleh L , Skinningsrud A , Swieten J C v , Verbeek M M , Wiltfang J , Younkin S , Scheltens P , Blankenstein M A
Published: April 2009

Background

Different cerebrospinal fluid (CSF) amyloid-beta 1–42 (A β1–42), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres.

Methods

Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured A β1–42, Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex.

Results

In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for A β1–42, Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest® ( N = 13) for A β1–42, lower interCV were calculated (22%). The centres that participated in both years ( N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008.

Conclusions

The highest variability was found for A β1–42. The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.
Stress cardiomyopathy – a unique presentation of diabetic ketoacidosis
Authors: Nanda Sudip , Longo Santo , Bhatt Surya Prakash , Pamula John , Sharma Shree Gopal , Dale Thompson H
Published: April 2009

We have documented a unique instance of diabetic ketoacidosis (DKA)-induced stress-related cardiomyopathy (CMP) in a 46-yr-old Caucasian female with type I diabetes mellitus. In times of stress, tissues with high capacity for aerobic metabolism, like myocardium, can preferentially change their metabolic substrate to ketones. The myocyte has a decreased ability to metabolize glucose and free fatty acids in stress CMP. To the best of our knowledge this is the first report of stress CMP complicating DKA. A possible mechanism for the same is hypothesized.
How should proteinuria be detected and measured?
Authors: Lamb Edmund J , MacKenzie Finlay , Stevens Paul E
Published: April 2009

Proteinuria is a classic sign of kidney disease and its presence carries powerful prognostic information. Although proteinuria testing is enshrined in clinical practice guidelines, there is surprising variation among such guidelines as to the definition of clinically significant proteinuria. There is also poor agreement as to whether proteinuria should be defined in terms of albumin or total protein loss, with a different approach being used to stratify diabetic and non-diabetic nephropathy. Further, the role of reagent strip devices in the detection and assessment of proteinuria is unclear. This review explores these issues in relation to recent national and international guidelines on chronic kidney disease (CKD) and epidemiological evidence linking proteinuria and clinical outcome. The authors argue that use of urinary albumin measurement as the front-line test for proteinuria detection offers the best chance of improving the sensitivity, quality and consistency of approach to the early detection and management of CKD.
Determination of the minimum alveolar concentration for halothane, isoflurane and sevoflurane in the gerbil
Authors: de Segura I A Gómez , de la Víbora J Benito , Criado A
Published: April 2009

The present work determined the minimum alveolar concentrations (MAC) of halothane, isoflurane and sevoflurane in adult female gerbils ( n = 24). Animals were placed in a chamber for anaesthetic induction before performing tracheal intubation. The tracheal tube was connected to a non-rebreathing circuit with minimal dead space. Body temperature, blood pressure, heart and respiratory rates and end-tidal volatile anaesthetic levels were measured continuously. MAC was determined using a standard noxious stimulus (tail-clamp). All experiments were performed at the same time of the day, body temperature was maintained constant and blood–gas analysis was performed to confirm that values were within normal limits. The mean ± SD MAC values were 1.06 ± 0.11% halothane ( n = 8), 1.55 ± 0.08% isoflurane ( n = 8) and 2.90 ± 0.12% sevoflurane ( n = 7). Cardiovascular parameters at 1× MAC did not differ significantly among anaesthetics but the respiratory rate was significantly higher in the halothane group than in the isoflurane and sevoflurane groups. The SpO2 values recorded throughout anaesthesia and the pH and partial oxygen pressure values determined at the end of the study did not differ among the studied anaesthetics at 1× MAC. These data suggest that the MAC for halogenated inhalant anaesthetics in gerbils is lower than the average MAC values obtained in rats and mice.
Blood collection from the sublingual vein in mice and hamsters: a suitable alternative to retrobulbar technique that provides large volumes and minimizes tissue damage
Authors: Heimann Maike , Käsermann Hans Peter , Pfister Rudolf , Roth Daniel Robert , Bürki Kurt
Published: April 2009

Blood examination is a key element in studies of laboratory animals. In rodents, retrobulbar venous plexus puncture is a commonly used method for obtaining a blood sample. Although this technique yields large volumes of blood, the disadvantage is that it can lead to severe tissue damage. The aim of the present study was to develop the puncture of V. sublingualis as a suitable alternative technique for drawing blood in mice and other rodents. In rats, this method has been established for collecting large blood volumes. During the first part of the study, the sublingual bleeding technique was developed for use in mice and hamsters. Guineapigs, however, do not have a sublingual vein; therefore, in this species the method is not possible. In the second part of the study, retrobulbar and sublingual methods were compared using male CD-1 mice. When compared with the retrobulbar method, sublingual venepuncture showed less tissue destruction in mice, with a decreased mean severity in the histological examination. In conclusion, sublingual venepuncture can be recommended as a suitable, alternative blood collection technique, because of the reduced risk of tissue damage in mice and hamsters.
Haemodynamic changes and stress responses of piglets to surgery during total intravenous anaesthesia with propofol and fentanyl
Authors: Schöffmann G , Winter P , Palme R , Pollak A , Trittenwein G , Golej J
Published: April 2009

The purpose of the study was to assess the haemodynamic (blood pressure and heart rate) changes and stress responses (serum cortisol and serum amyloid A [SAA] concentrations) to surgery in piglets during total intravenous anaesthesia (TIVA) with propofol and fentanyl. After preanaesthetic medication with intramuscular midazolam (0.5 mg/kg body mass), ketamine (10 mg/kg) and butorphanol (0.5 mg/kg) anaesthesia was induced in five piglets, with intravenous propofol (1 mg/kg) followed by tracheal intubation and mechanical lung ventilation. Soft tissue surgery was performed in the jugular and inguinal regions during TIVA with propofol (8 mg/kg/h) and fentanyl (35 μg/kg/h). Anaesthesia was maintained for 300 min after surgery as the piglets were the control group of a project involving extracorporeal membrane oxygenation. Mean plasma cortisol concentration decreased significantly ( P < 0.05) from 59 ± 39.9 nmol/L (mean ± 1 SD) before surgery to 7.5 ± 2.5 nmol/L 300 min after end of surgical procedure. The mean SAA concentrations increased over the same period from 1.6 ± 2.3 μg/mL to 4.2 ± 5.6 μg/mL without statistical significance. The baseline (presurgery) mean arterial pressure (MAP) was 72 ± 9 mmHg compared with 72 ± 11 mmHg 300 min after end of surgery. Neither heart rate nor lactate concentrations changed significantly over the same time points: heart rate was 104 ± 11 and 103 ± 15 beats/min whereas mean lactate concentrations were reduced from 1.14 ± 0.45 mmol/L to 0.90 ± 0.22 mmol/L. Haemodynamic stability, a decrease in serum cortisol and a non-statistically significant rise in mean SAA concentrations suggest that the anaesthetic described suppresses the stress response of piglets to surgery without adverse cardiovascular effects. Therefore, it may prove useful in cardiovascular research.
An interview study of phenotypic characterization of genetically-modified mice
Authors: Thon R , Vondeling H , Lassen J , Hansen A K , Ritskes-Hoitinga M
Published: April 2009

An interview study was carried out with the aim of clarifying the reasons for the limited use of phenotypic characterization of genetically-modified mice (GMM) and identifying issues hindering its implementation. A total of 15 users of GMM participated in semi-structured face-to-face interviews, which were audio-taped and transcribed. The results were extracted using content analysis by theme. The investigation confirmed that few animals were systematically phenotyped and an observational approach was found to be widespread. The primary interest of the interviewees was phenotyping for impaired animal welfare. The concept of phenotyping was widely understood and perceived as a scientific advantage. The comprehensiveness of the protocols and the resources required for phenotyping were seen as problematic. All participants addressed this issue, be it regarding lack of time, money or expertise. Also, among the negative statements were worries about the capability of the available protocols to produce the information needed by the individual scientist. Phenotyping was predicted to become much more widespread in the future and its success was expected to depend on the development of reliable, fast and inexpensive methods. The study identified different aims of phenotyping and the suitability of the published protocols for these purposes was discussed. The contradiction between the limited use of characterization and its advantages was also discussed and proposals for the improvement of future phenotyping strategies are formulated.
Mycobacterium gordonae infection in a colony of African clawed frogs (Xenopus tropicalis)
Authors: Sánchez-Morgado José M , Gallagher Alec , Johnson Linda K
Published: April 2009

Mycobacterium gordonae is an occasional human pathogen associated with cutaneous infections and nodular granulomatous skin lesions. A case of cutaneous nodular infection caused by M. gordonae in a colony of African clawed frogs ( Xenopus tropicalis) is described and confirms this organism to be an opportunistic frog pathogen.
A new small animal model for the study of spine fusion in the sand rat: pilot studies
Authors: Gruber Helen E , Gordon Brian , Williams Cliff , Ingram Jane A , Norton H James , Hanley Edward N
Published: April 2009

Spine fusion is used to treat traumatic or degenerative lumbar instability in the cervical or lumbar spine. Although degenerative radiological changes in discs adjacent to a fusion have been well-recognized, histopathological changes in adjacent discs have not been studied and are poorly understood. An economical small animal model for lumbar fusion would be a useful research tool. Study objectives were to: (1) develop a model of non-instrumented spine fusion in the sand rat, a rodent with spontaneous, age-related disc degeneration; (2) use radiological–histological analyses to study fusion and disc degeneration in cranial and caudal discs adjacent to the fusion. Studies were approved by our Institutional Animal Care and Use Committee. A small segment of outer annulus tissue was surgically removed from lumbar discs, radiographs obtained and the animal allowed to recover and age. At surgical harvest, radiographs of 28 spine fusion specimens were scored and statistically analysed for adjacent disc space narrowing, wedging, endplate sclerosis and irregular disc margins. At harvest, the incidence of these radiological indices of disc degeneration were significantly greater than at time of surgery. Pilot studies presented here indicate that this model provides a novel addition to basic science approaches studying the clinically important topic of spinal fusion and adjacent segment changes. The resulting fusion site can be assessed statistically with radiological scoring to determine development/progression of disc degeneration in adjacent segments, and correlative histological features can be examined. The sand rat is well-suited for use in spine fusion studies because of reliable/reproducible progression of disc degeneration and the favourable economics of small rodent studies.