Influence of Ibuprofen on Phospholipid Membranes

Basic understanding of biological membranes is of paramount importance as these membranes comprise the very building blocks of life itself. Cells depend in their function on a range of properties of the membrane, which are important for the stability and function of the cell, information and nutrient transport, waste disposal and finally the admission of drugs into the cell and also the deflection of bacteria and viruses. We have investigated the influence of ibuprofen on the structure and dynamics of L-alpha-phosphatidylcholine (SoyPC) membranes by means of grazing incidence small-angle neutron scattering (GISANS), neutron reflectometry and grazing incidence neutron spin echo spectroscopy (GINSES). From the results of these experiments we were able to determine that ibuprofen induces a two-step structuring behavior in the SoyPC films, where the structure evolves from the purely lamellar phase for pure SoyPC over a superposition of two hexagonal phases to a purely hexago- nal phase at high concentrations. Additionally, introduction of ibuprofen stiffens the membranes. This behavior may be instrumental in explaining the toxic behavior of ibuprofen in long-term application.Comment: -Improved indexing in Fig. 4e) -changed concentrations to mol% -improved arguments, however conclusions stay unchange

Strange matter prospects within the string-flip model

In this contribution we extend the recently developed two-flavor quark-matter string-flip model by including strange quarks. We discuss implications for compact stars.Comment: 4 pages, 4 figures, proceedings to SQM201

Ten-Year Minimum Follow-up Study of First Metatarsophalangeal Joint Fusion in Young vs Old Patients

BACKGROUND Painful degenerative joint disease (DJD) of the first metatarsophalangeal joint (MTP I), or hallux rigidus, mainly occurs in later stages of life. For end-stage hallux rigidus, MTP I arthrodesis is considered the gold standard. As young and active patients are affected considerably less frequently, it currently remains unclear, whether they benefit to the same extent. We hypothesized that MTP I arthrodesis in younger patients would lead to an inferior outcome with decreased rates of overall with lower rates of patient postoperative pain and function compared to an older cohort. METHODS All patients aged 60 years. Minimum follow-up was 10 years. Outcome measures were Tegner activity score (TAS), a "Virtual Tegner activity score" (VTAS), the visual analog scale (VAS), and the Foot Function index (FFI). RESULTS Sixty-one MTP I fusions (n = 28 young, n = 33 old) in 46 patients were included in our study at an average of 14 years after surgery. Younger patients experienced significantly more pain relief as reflected by changes in VAS and FFI Pain subscale scores. No difference in functional outcomes was found with change in the FFI function subscale or in the ability to have desired functional outcomes using the ratio of TAS to VTAS. Revision rate did not differ between the two groups apart from hardware removal, which was significantly more likely in the younger group. CONCLUSION In patients below the age of 50 years with end-stage DJD of the first metatarsal joint, MTP I arthrodesis not only yielded highly satisfactory postoperative results at least equal outcome compared to an older cohort of patients aged >60 years at an average 14 years' follow-up. Based on these findings, we consider first metatarsal joint fusion even for young patients is a valid option to treat end-stage hallux rigidus. LEVEL OF EVIDENCE Level III, a case-control study

Impact of Different Catheter Lock Strategies on Bacterial Colonization of Permanent Central Venous Hemodialysis Catheters

Thirty-nine hemodialysis patients with permanent central venous catheters were analyzed for bacterial catheter colonization comparing different catheter-lock strategies. The closed needleless Tego connector with sodium chloride lock solution was significantly more frequently colonized with bacteria than the standard catheter caps with antimicrobially active citrate lock solution (odds ratio, 0.22 [95% confidence interval, 0.07-0.71]; P = .011

Biological outcome measurements for behavioral interventions in multiple sclerosis

Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms of MS are at least partially mediated by biological processes such as inflammation, neuroendocrine dysfunction or regional brain damage. Thus, successful treatment of these symptoms with behavioral approaches could potentially also affect the underlying biology. Rigidly designed scientific studies are needed to explore the potential of such interventions to affect MS pathology and biological pathways linked to psychological and neuropsychiatric symptoms of MS. Such studies need to carefully select outcome measures on the behavioral level that are likely to be influenced by the specific intervention strategy and should include biomarkers with evidence for an association with the outcome parameter in question. In this overview, we illustrate how biological and psychological outcome parameters can be combined to evaluate behavioral interventions. We focus on two areas of interest as potential targets for behavioral interventions: depression and fatigue

Computing the shortest elementary flux modes in genome-scale metabolic networks

This article is available open access through the publisher’s website through the link below. Copyright @ The Author 2009.Motivation: Elementary flux modes (EFMs) represent a key concept to analyze metabolic networks from a pathway-oriented perspective. In spite of considerable work in this field, the computation of the full set of elementary flux modes in large-scale metabolic networks still constitutes a challenging issue due to its underlying combinatorial complexity. Results: In this article, we illustrate that the full set of EFMs can be enumerated in increasing order of number of reactions via integer linear programming. In this light, we present a novel procedure to efficiently determine the K-shortest EFMs in large-scale metabolic networks. Our method was applied to find the K-shortest EFMs that produce lysine in the genome-scale metabolic networks of Escherichia coli and Corynebacterium glutamicum. A detailed analysis of the biological significance of the K-shortest EFMs was conducted, finding that glucose catabolism, ammonium assimilation, lysine anabolism and cofactor balancing were correctly predicted. The work presented here represents an important step forward in the analysis and computation of EFMs for large-scale metabolic networks, where traditional methods fail for networks of even moderate size. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online (http://bioinformatics.oxfordjournals.org/cgi/content/full/btp564/DC1).Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (FCT) and Siemens SA Portugal

Reassessment of CXCR4 Chemokine Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-2

BACKGROUND: The CXCR4 chemokine receptor regulates migration and homing of cancer cells to specific metastatic sites. Determination of the CXCR4 receptor status will provide predictive information for disease prognosis and possible therapeutic intervention. However, previous attempts to localize CXCR4 using poorly characterized mouse monoclonal or rabbit polyclonal antibodies have produced predominant nuclear and occasional cytoplasmic staining but did not result in the identification of bona fide cell surface receptors. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we extensively characterized the novel rabbit monoclonal anti-CXCR4 antibody (clone UMB-2) using transfected cells and tissues from CXCR4-deficient mice. Specificity of UMB-2 was demonstrated by cell surface staining of CXCR4-transfected cells; translocation of CXCR4 immunostaining after agonist exposure; detection of a broad band migrating at M(r) 38,000-43,000 in Western blots of homogenates from CXCR4-expressing cells; selective detection of the receptor in tissues from CXCR4+/+ but not from CXCR4-/- mice; and abolition of tissue immunostaining by preadsorption of UMB-2 with its immunizing peptide. In formalin-fixed, paraffin-embedded human tumor tissues, UMB-2 yielded highly effective plasma membrane staining of a subpopulation of tumor cells, which were often heterogeneously distributed throughout the tumor. A comparative analysis of the mouse monoclonal antibody 12G5 and other frequently used commercially available antibodies revealed that none of these was able to detect CXCR4 under otherwise identical conditions. CONCLUSIONS/SIGNIFICANCE: Thus, the rabbit monoclonal antibody UMB-2 may prove of great value in the assessment of the CXCR4 receptor status in a variety of human tumors during routine histopathological examination

High-Pressure Transformation of SiO2 Glass from a Tetrahedral to an Octahedral Network:A Joint Approach Using Neutron Diffraction and Molecular Dynamics

International audienceA combination of in situ high-pressure neutron diffraction at pressures up to 17.5(5) GPa and moleculardynamics simulations employing a many-body interatomic potential model is used to investigate thestructure of cold-compressed silica glass. The simulations give a good account of the neutron diffractionresults and of existing x-ray diffraction results at pressures up to ∼60 GPa. On the basis of the moleculardynamics results, an atomistic model for densification is proposed in which rings are “zipped” by a pairingof five- and/or sixfold coordinated Si sites. The model gives an accurate description for the dependence ofthe mean primitive ring size hni on the mean Si-O coordination number, thereby linking a parameter that issensitive to ordering on multiple length scales to a readily measurable parameter that describes the localcoordination environment

CT mapping of the vertebral level of right adrenal vein

PURPOSEWe aimed to evaluate the accuracy of multidetector computed tomography (MDCT) venous mapping for the localization of the right adrenal veins (RAV) in patients suffering from primary aldosteronism.METHODSMDCT scans of 75 patients with primary aldosteronism between March 2008 and November 2011 were evaluated by two readers (a junior [R1] and a senior [R2] radiologist) according to the following criteria: quality of RAV depiction (scale, 1–5), localization of the RAV confluence with regard to the inferior vena cava, and depiction of anatomical variants. Results were compared with RAV venograms obtained during adrenal vein sampling and corroborated by laboratory testing of cortisol in selective RAV blood samples. Kappa statistics were calculated for interobserver agreement and for concordance of MDCT mapping with the gold standard.RESULTSSuccessful RAV sampling was achieved in 69 of 75 patients (92%). Using MDCT mapping, adrenal veins could be visualized in 78% (R1, 54/69) and 77% (R2, 53/69) of patients. MDCT mapping led to correct identification of RAV in 70% (R1, 48/69) and 88% (R2, 61/69) of patients. Venograms revealed five cases of anatomical variants, which were correctly identified in 60% (R1, R2). MDCT-based localizations were false or misleading in 16% (R1, 11/69) and 7% (R2, 5/69) of cases.CONCLUSIONPreinterventional MDCT mapping may facilitate successful catheterization in adrenal vein sampling