Peripherally Inserted Central Catheters-associated blood stream infections-occurrence, risk factors, and pathogens, a single center study.

Background: Peripherally inserted central catheters (PICCs) are central venous catheters inserted peripherally but terminate in great vessels. PICCs are widely used for patients requiring long-term intravenous therapy in both in-patient and out-patient settings. Aim: This study was carried out to understand PICC-related complications, specifically infections and causal pathogens, in a tertiary care hospital in Kerala, South India. Methods: A retrospective analysis of PICC insertions and follow-up during a 9 years period to look at patient demographics and infections related to PICC was carried out. Results: The overall PICC-related complication rate is 28.1% (4.98 per 1000 PICC days). Commonest complication was thrombosis followed by infection, either PICC-associated bloodstream infection (PABSI) or local infection (LI). PABSI noted in this study was 1.34 per 1000 catheter days. The majority (85%) of PABSI were due to Gram-negative rods. The average duration of PICC days for occurrence of PABSI was 14 days and the majority occurred in in-patients. Conclusion: Thrombosis and infection were the commonest PICC-related complications. PABSI rate was comparable to that of previous studies.

Umeclidinium in chronic obstructive pulmonary disease: latest evidence and place in therapy.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and health care expenditure throughout the world. COPD guidelines recommend the use of long-acting muscarinic antagonist (LAMA) either alone or in combination with a long-acting ß2 agonist (LABA). For over 10 years, tiotropium was the only LAMA that was used in the management of COPD. Over the past few years, various new drugs have been identified that act on the muscarinic receptors and ß2 receptors. Umeclidinium (Umec) is a new LAMA currently approved for use in patients with COPD either as monotherapy or in combination with vilanterol (Vil). Both Umec alone and in combination with Vil delivered through a multi-dose dry powder Ellipta™ device have shown improvement in lung function, health-related quality of life and exacerbation frequency in patients with COPD. This review provides an overview of the pharmacology, pharmacodynamics and pharmacokinetics of Umec, and evaluates the clinical efficacy and safety studies in patients with COPD.

Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation.

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

Effects of arsenite stress on growth and proteome of Klebsiella pneumoniae.

In the present study an arsenite, As(III), tolerating bacterium, MR4, was isolated from Mulla River Pune, India, capable of reducing arsenate to arsenite and identified as Klebsiella pneumoniae (HQ857583). Comparative proteomic analysis using two-dimensional gel electrophoresis (2-DGE) and matrix assisted laser desorption ionization-time of flight-time of flight (MALDI-TOF/TOF) was used to monitor the proteins undergoing changes in expression levels under 2.5 mM As(III) stress. The 2-DGE proteome map has shown that 60 proteins were differentially expressed under As(III) stress, of which 39 proteins were successfully identified with a MASCOT score greater than 70 (p<0.05). Among the identified proteins, membrane transport/binding proteins, porins, and amino acid metabolism enzymes were down-regulated while stress responsive proteins and antioxidant enzymes were up-regulated. Proteins involved in carbohydrate metabolism, particularly those in pentose phosphate pathway were also up-regulated while those involved in pyruvate metabolism were down-regulated. However, proteins involved in glycolysis and tricarboxylic acid cycle showed a mixed regulation response. These findings provide new insights into the probable mechanisms by which K. pneumoniae (HQ857583) could be adapting to As(III) stress.

"Zoom-ln"--A targeted database search for identification of glycation modifications analyzed by untargeted tandem mass spectrometry.

Post-translational modifications (PTMs) are very important to biological function, however their identification and characterization is technically challenging. In this study, we have identified glycation modifications by nano LC-MSE, a data independent acquisition work flow, followed by database search using the Protein Lynx Global Server (PLGSJ). PLGS search with a complete human protein database hardly identified glycation modifications in a glycated human serum albumin (HSA), which was detected to be glycated by western blotting with advanced glycation end products (AGE) antibody and fluorescence spectroscopy. To overcome this difficulty, "Zoom-In" approach, a targeted database search was used to identify glycation modifications in a glycated HSA, which were further manually validated. This approach was useful for identification of glycation modifications from untargeted tandem mass spectrometryworkflow such as MSE, but may require the development of a new algorithm or an upgrade of the existing software.

Anti-IgE in allergic asthma and rhinitis: an update.

Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.