US-guided retrograde tibial artery puncture for recanalization of complex infrainguinal arterial occlusions

PURPOSEWe aimed to describe the technical aspects and outcomes of the retrograde tibial approach and balloon predilation for recanalization of complex infrainguinal arterial occlusions and determine the efficacy of this approach in minimizing failure rates. MATERIALS AND METHODSBetween September 2006 and April 2011, antegrade revascularization failed in 22 limbs with complex total occlusions within the infrainguinal arterial territory. For each of these antegrade failure cases in 22 patients, a retrograde tibial puncture had been attempted. Percutaneous recanalization and predilation were initially performed through tibial access, and final balloon dilatation or stent placement was performed from antegrade femoral access. The patients were followed up for functionality and wound healing. RESULTSAccess from the tibial artery was successfully obtained for all patients (100%). Successful recanalization was obtained in 18 patients (82%). Retrograde access was performed from the anterior tibial/dorsalis pedis artery in 12 patients and posterior tibial artery in 10 patients. One major and one minor complications were documented. CONCLUSIONRetrograde tibial recanalization technique in the infrainguinal complex arterial occlusion safely increases the success rates of percutaneous recanalization in the failed traditional approach and is a feasible endovascular option to avoid more invasive, time-consuming, and high-risk procedures

Improved homology-driven computational validation of protein-protein interactions motivated by the evolutionary gene duplication and divergence hypothesis

<p>Abstract</p> <p>Background</p> <p>Protein-protein interaction (PPI) data sets generated by high-throughput experiments are contaminated by large numbers of erroneous PPIs. Therefore, computational methods for PPI validation are necessary to improve the quality of such data sets. Against the background of the theory that most extant PPIs arose as a consequence of gene duplication, the sensitive search for homologous PPIs, i.e. for PPIs descending from a common ancestral PPI, should be a successful strategy for PPI validation.</p> <p>Results</p> <p>To validate an experimentally observed PPI, we combine FASTA and PSI-BLAST to perform a sensitive sequence-based search for pairs of interacting homologous proteins within a large, integrated PPI database. A novel scoring scheme that incorporates both quality and quantity of all observed matches allows us (1) to consider also tentative paralogs and orthologs in this analysis and (2) to combine search results from more than one homology detection method. ROC curves illustrate the high efficacy of this approach and its improvement over other homology-based validation methods.</p> <p>Conclusion</p> <p>New PPIs are primarily derived from preexisting PPIs and not invented <it>de novo</it>. Thus, the hallmark of true PPIs is the existence of homologous PPIs. The sensitive search for homologous PPIs within a large body of known PPIs is an efficient strategy to separate biologically relevant PPIs from the many spurious PPIs reported by high-throughput experiments.</p

Effect of Long Term Oral Warfarin Sodium Treatment on Bone Mineral Density Scores and Spinal Sagittal Alignment

Objective: The aim of this study was to investigate the effect of long term oral warfarin sodium treatment on bone mineral density (BMD) and spinal sagittal alignment. Materials and Methods: Sixty four participants were enrolled for this retrospective study. Participants were divided into two groups-participants who had taken warfarin sodium for at least two years (n=33) and participants who had never taken warfarin sodium (n=31). All of the individuals were evaluated at the same center. Dual X-ray absorptiometry (DXA) was used for measuring BMD. Whole spine x-rays were obtained for sagittal assessment and the following parameters were measured: Cervical lordosis, thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope and sagittal vertical axis (SVA). Results: The mean BMD value was significantly higher in participants who had not taken warfarin sodium compared to participants who had taken warfarin sodium. The differences between the average values were 0.1552 g/cm2 in BMD; 2.1 in T scores; 1.4 in Z scores. On the radiological evaluation of the spine, cervical lordosis was 7.1 degrees lower, lumbar lordosis was 4.7 degrees lower and thoracic kyphosis was 5.3 degrees higher in the patients using drug. C7 plumb line was interchanged forward in the patients using drug. Conclusions: This study shows that warfarin sodium use worsens bone quality in the lumbar region and does not affect bone quality in the femoral region. Furthermore, warfarin sodium use also reduces physiological lordosis and enhances thoracic kyphosis. Consequences of these changes are the likely cause of sagittal spinal anterior imbalance. Long-term oral warfarin sodium use affect bone mineral density and spinal alignment. Our conclusion about giving clear message and show exactly mechanism we need prospective randomized multicentre studies in future. We strongly believe this study will be pioneer for future researches

InSilico Proteomics System: Integration and Application of Protein and Protein-Protein Interaction Data using Microsoft .NET

In the last decades, biological databases became the major knowledge resource for researchers in the field of molecular biology. The distribution of information among these databases is one of the major problems. An overview about the subject area of data access and representation of protein and protein-protein interaction data within public biological databases is described. For a comprehensive and consistent way of searching and analysing integrated protein and protein-protein interaction data, the InSilico Proteomics (ISP) project has been initiated. Its three main objectives are (1) to provide an integrated knowledge pool for data investigation and global network analysis functions for a better understanding of a cell’s interactome, (2) employment of public data for plausibility analysis and validation of in-house experimental data and (3) testing the applicability of Microsoft’s .NET architecture for bioinformatics applications. Data integrated into the ISP database can be queried through the Web portal PRIMOS (PRotein Interaction and MOlecule Search) which is freely available at http://biomis.fh-hagenberg.at/isp/primos

The influence of commonly used tags on structural propensities and internal dynamics of peptides

The influence of biotin and fluorescein tags attached to the N-terminus of peptides on their structural propensities is assessed by NMR methods. While the small peptides investigated are highly mobile with no uniquely preferred conformation, the introduction of the tags, in particular hydrophobic ones, clearly shows an influence on NMR parameters such as chemical shifts and relaxation properties, which are not restricted to the nearby residues, but also affect distant parts. Thus, long-range effects on structural propensities become evident and are cause for concern with respect to the interpretation of weak interaction tests, which rely upon the assumption that tags do not exert influence on intermolecular interactions.(VLID)363463

A direct quantitative PCR-based measurement of herpes simplex virus susceptibility to antiviral drugs and neutralizing antibodies

Herpes simplex viruses (HSV) are common human pathogens that can cause painful but benign manifestations and recurrent complaints, but can also cause significant morbidity and mortality on infection of the eye or brain and with disseminated infection of an immunosuppressed patient or a neonate. HSV growth inhibition measurement by plaque or yield reduction is a key task in the development of novel antiviral compounds but the manual methods are very labour intensive. The sensitive and specific PCR technology could be an effective method for quantitation of HSV DNA related to virus replication; however the currently described PCR approaches have a major limitation, namely the requirement of purification of DNA from the infected cells. This limitation makes this approach unfeasible for high-throughput screenings. The monitoring of HSV specific antibody titre is essential in vaccination trials and in the improvement of HSV-based oncolytic virotherapy. Usually, conventional cytopathic effect-based and plaque reduction neutralization tests are applied to measure the neutralization titre, but these methods are also time-consuming. To overcome this, we developed a quantitative PCR (qPCR) method for the detection of HSV-2 DNA directly from the infected cells (direct qPCR) and the method was further adapted to measure the titre of HSV specific neutralizing antibody in human sera. The conditions of direct qPCR assay were optimized to measure the antiviral activity of known and novel antiviral substances. Using HSV-2 seronegative and seropositive patients' sera, the validity of the direct qPCR neutralization test was compared to traditional cytopathic effect-based assay. The direct qPCR method was able to detect the HSV-2 DNA quantitatively between multiplicity of infection 1/64 and 1/4194304, indicating that the dynamic range of the detection was approximately 65,500 fold with high correlation between the biological and technical replicates. As a proof of the adaptability of the method, we applied the direct qPCR for antiviral inhibitory concentration 50 (IC50) measurements of known and novel antiviral compounds. The measured IC50 of acyclovir was approximately 0.28mug/ml, similar to the previously published IC50 value. The IC50 of novel antiviral candidates was between 1.6-3.1mug/ml. The direct qPCR-based neutralization titres of HSV positive sera were 1:32-1:64, identical to the neutralization titres determined using a traditional neutralization assay. The negative sera did not inhibit the HSV-2 replication in either of the tests. Our direct qPCR method for the HSV-2 growth determination of antiviral IC50 and neutralization titre is less time-consuming, less subjective and a more accurate alternative to the traditional plaque titration and growth reduction assays