1.
A novel family of peptides with potent activity against influenza A viruses.
Source
University of Edinburgh.
Abstract
The emergence of drug resistant strains of influenza virus has catalyzed a search for new antiviral agents to supplement or replace existing drugs. Following the success of the HIV entry blocker Enfuvirtide, there has been a resurgence of interest in peptide based antivirals. In this paper we report on the discovery of a novel family of peptides (FluPep, FP) that function as inhibitors of influenza A virus infection. The prototype peptide (FP1, also known as Tkip) interacts with haemagglutinin and inhibits the binding of the virus to cell membranes. Using a plaque reduction assay we have demonstrated that a variety of influenza A virus subtypes (including H1N1, H3N2 H5N1) are inhibited by FluPep and its derivatives at nanomolar concentrations. By truncating FluPep we have identified a minimal sequence of 6 amino acids that binds to HA and inhibits infection. Using a mouse model of intranasal influenza virus infection we observed potent inhibition of virus infection when peptide is given at the time of virus administration. These data indicate that FluPep is a highly effective anti-influenza agent with the potential to translate to the clinic.
DNA Display Selection of Peptide Ligands for a Full-Length Human G Protein-Coupled Receptor on CHO-K1 Cells.
Source
Department of Biosciences and Informatics, Keio University, Yokohama, Japan.
Abstract
The G protein-coupled receptors (GPCRs), which form the largest group of transmembrane proteins involved in signal transduction, are major targets of currently available drugs. Thus, the search for cognate and surrogate peptide ligands for GPCRs is of both basic and therapeutic interest. Here we describe the application of an in vitro DNA display technology to screening libraries of peptide ligands for full-length GPCRs expressed on whole cells. We used human angiotensin II (Ang II) type-1 receptor (hAT1R) as a model GPCR. Under improved selection conditions using hAT1R-expressing Chinese hamster ovary (CHO)-K1 cells as bait, we confirmed that Ang II gene could be enriched more than 10,000-fold after four rounds of selection. Further, we successfully selected diverse Ang II-like peptides from randomizedpeptide libraries. The results provide more precise information on the sequence-function relationships of hAT1R ligands than can be obtained by conventional alanine-scanning mutagenesis. Completely in vitro DNA display can overcome the limitations of current display technologies and is expected to prove widely useful for screening diverse libraries of mutantpeptide and protein ligands for receptors that can be expressed functionally on the surface of CHO-K1 cells.
Evaluation of COMU as a coupling reagent for in situ neutralization Boc solid phase peptide synthesis.
Source
Institute for Molecular Bioscience, The University of Queensland, St Lucia, 4072, Australia; Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center, Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus, Denmark.
Abstract
Benzotriazole-based coupling reagents have dominated the last two decades of solid phase peptide synthesis. However, a growing interest in synthesizing complex peptides has stimulated the search for more efficient and low-cost coupling reagents, such as COMU which has been introduced as a nonexplosive alternative to the classic benzotriazole coupling reagents. Here, we present a comparative study of the coupling efficiency of COMU with the benzotriazole-based HBTU and HCTU for use in in situ neutralization Boc-SPPS. Difficult sequences, such as ACP(65-74), Jung-Redeman 10-mer, and HIV-1 PR(81-99), were used as model target peptides on polystyrene-based resins, as well as polyethylene glycol-based resins. Coupling yields obtained using fast in situ Boc-SPPS cycles were determined with the quantitative ninhydrin test as well as via LC-MS analysis of the crude cleavage products. Our results demonstrate that COMU coupling efficiency was less effective compared to HBTU and HCTU with HCTU ≥ HBTU > COMU, when polystyrene-based resins were employed. However, when the PEG resin was employed in combination with a safety catch amide (SCAL) linker, more comparable yields were observed for the three coupling reagents with the same ranking HCTU ≥ HBTU > COMU. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome.
Source
Department of Biochemistry, Lady Hardinge Medical College, New Delhi-110001, India.
Abstract
BACKGROUND:
The cachexia anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, weight loss, anorexia, early satiety, fatigue, weakness due to shifts in metabolism caused by tumour by-products and cytokines. Various neuropeptides like Leptin, neuropeptide Y, melanocortin, agouti-related peptides have been known to regulate appetite and body weight.
METHOD:
A comprehensive literature search was carried out on the websites of Pubmed Central (http://www.pubmedcentral.nih.gov/), National Library of Medicine (http://www.ncbl.nlm.nih.gov) and various other net resources.
RESULT:
Data from observational studies shows that various cytokines (TNF-α, IL-6 and IL-1) are associated with metabolic changes resulting in cachexia in cancer patients. These cytokines may mimic the action of various neuropeptides resulting in anorexia, various metabolic effects resulting from enhanced catabolic state and weight loss.
CONCLUSION:
There is a need to understand and explore the role of various neuropeptides and cytokines in the pathophysiology of cancer-anorexia syndrome so that therapeutic measures may be designed for effective palliative care.
Copyright © 2011. Published by Elsevier B.V.
Bioactive compounds with effects on inflammation markers in humans.
Source
Division of Clinical Nutrition, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil.
Abstract
Obesity and other chronic diseases are accompanied by adipose tissue, liver, pancreas, muscle and brain low-grade chronic inflammation. Indeed, the obese condition and metabolic syndrome are characterized by an increased expression of inflammatory cytokines and infiltration of immune cells in adipocytes. The inflammatory response promotes the activation of transcriptional factors and pro-inflammatory cytokines, which can lead to an unresolved inflammatory response associated with an inhibition of insulin signalling and high risk for cardiovascular events. Epidemiological and intervention studies have been carried out to find out dietary patterns, foods and bioactive compounds with protective anti-inflammatory actions. The most studied compounds are polyphenols, especially isoflavone and anthocyanin, but quercertin, catechin and resveratrol have also been investigated. Furthermore, some studies have reported the effects of milk peptides, plant sterol and stanol, l-carnitine and α-lipoic acid on inflammatory processes. This review aimed to collect and discuss those relevant studies reported in the scientific literature following a systematic scientific search about the effect of such bioactive compounds on inflammation in humans.
Short read sequencing for genomic analysis of the brown rot fungus Fibroporia radiculosa.
Source
Forest Products, Mississippi State University, MS.
Abstract
The feasibility of short read sequencing for genomic analysis was demonstrated for Fibroporia radiculosa, a copper-tolerant fungus that causes brown rot decay of wood. The effect of read quality on genomic assembly was assessed by filtering Illumina GAIIx reads from a single run of a paired-end library (75 nt read length, 300 bp fragment size) to three different stringency levels, and then assembling each dataset with Velvet. A simple approach was devised to determine which filter stringency was "best". Venn diagrams identified the regions containing reads that were used in an assembly, but were of low enough quality to be removed by a filter. By plotting base quality histograms of reads in this region, we judged whether a filter was too stringent or not stringent enough. Our best assembly had a genome size of 33.6 Mb, N50 = 65.8 kb for kmer = 51, and maximum contig length of 347 kb. Using GeneMark, 9262 genes were predicted. TargetP and SignalP analysis showed that among the 1213 genes with secreted products, 986 had motifs for signalpeptides and 227 for signal anchors. Blast2GO analysis provided functional annotation for 5407 genes. We identified 29 genes with putative roles in copper tolerance and 74 genes for lignocellulose degradation. A search for homologs of these 103 genes showed that F. radiculosa exhibited more similarity to Postia placenta than Serpula lacrymans. Notable differences were found, however, and their involvement in copper tolerance and wood decay are discussed.
In-silico characterization of ECE-1 inhibitors.
Source
R.G. Biosciences, Visakhapatnam, India.
Abstract
Atherosclerosis is the primary cause of CAD and cerebrovascular disease. Endothelin (ET)-1 is a vasoconstrictivepeptide implicated in Atherosclerosis pathology. Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin. Reported inhibitors of ECE-1 and their IC(50) values were retrieved from literature and their structures were docked with the parent protein using the Molegro virtual docker. The obtained MolDock scores of each of the compounds are hereby reported and are subject to graphical analysis in conjunction with their respective IC(50) values to characterize potent inhibitors. A search was then run in the ZINC database for compounds with similar properties. Potent inhibitors with higher Dock scores and better Ranking were isolated and are reported.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Semi-Automated Identification of N-Glycopeptides by Hydrophilic Interaction Chromatography, nano-Reverse-Phase LC-MS/MS, and Glycan DatabaseSearch.
Abstract
Glycoproteins fulfill many indispensable biological functions and changes in protein glycosylation have been observed in various diseases. Improved analytical methods are needed to allow a complete characterization of this complex and common posttranslational modification. In this study, we present a workflow for the analysis of the microheterogeneity of N-glycoproteins which couples hydrophilic interaction and nano-reverse-phase C18 chromatography to tandem QTOF mass spectrometric analysis. A glycan database search program, GlycoPeptideSearch, was developed to match N-glycopeptide MS/MS spectra with the glycopeptides comprised of a glycan drawn from the GlycomeDB glycan structure database and a peptide from a user-specified set of potentially glycosylated peptides. Application of the workflow to human haptoglobin and hemopexin, two microheterogeneous N-glycoproteins, identified a total of 57 distinct site-specific glycoforms in the case of haptoglobin and 14 site-specific glycoforms of hemopexin. Using glycan oxonium ions, peptide-characteristic glycopeptide fragment ions, and by collapsing topologically redundant glycans, the searchsoftware was able to make unique N-glycopeptide assignments for 51% of assigned spectra, with the remaining assignments primarily representing isobaric topological rearrangements. The optimized workflow, coupled with GlycoPeptideSearch, is expected to make high-throughput semi-automated glycopeptide identification feasible for a wide range of users.
Clinical efficacy and safety of once-weekly glucagon-like Peptide-1 agonists in development for treatment of type 2 diabetes mellitus in adults.
Source
Cabarrus Family Medicine, Harrisburg, NC.
Abstract
OBJECTIVE:
To review pharmacologic, pharmacokinetic, efficacy, and safety data of once-weekly glucagon-likepeptide-1 (GLP-1) agonists exenatide long-acting release (LAR), albiglutide, and taspoglutide in treatment of type 2 diabetes mellitus (T2DM).
DATA SOURCES:
A MEDLINE search (1966-August 2011) was conducted using the following key words: type 2 diabetes mellitus, glucagon-like peptide-1 agonists once weekly, glucagon-like peptide-1 agonists, exenatide LAR, albiglutide, and taspoglutide.
STUDY SELECTION AND DATA EXTRACTION:
All articles published in English identified from the data sources were evaluated, prioritizing randomized controlled trials with human data. The references of published articles identified were examined for additional studies appropriate for the review.
DATA SYNTHESIS:
Native GLP-1 increases glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying in healthy individuals, but these effects may be blunted in patients with T2DM. Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV, it is not a practical treatment option. Currently, 2 GLP-1 receptor agonists have been approved by the Food and Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives. These agents have shown significant improvements in hemoglobin A(1c), fasting plasma glucose, and postprandial plasma glucose, as well as improvements in body weight, blood pressure, and lipid parameters. These agents allow for less-frequent dosing schedules, improved glycemic control throughout the day, and improved treatment satisfaction compared to some available agents. GLP-1 agonists have been well tolerated, with the most common adverse effects being gastrointestinal related, which occurred early in therapy but typically resolved after 4-8 weeks. The incidence of hypoglycemia was infrequent and mild during therapy.
CONCLUSIONS:
Once-weekly GLP-1 agonists provide similar glycemic control with weight reduction, as well as overall higher treatment satisfaction for patients because of their ease of use and need for less-frequent dosing compared to some available agents.
Changes in fibrinopeptide A peptides in the sera of rats chronically exposed to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Source
Department of Occupational Health, School of Public Health, Tianjin Medical University, Qixiangtai Road No. 22, Heping District, Tianjin 300070, China.
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine disruptors. To investigate peptidechanges in the sera of rats chronically exposed to TCDD and to explore the association of these changes with liver morphology, TCDD was administrated to male rats at doses of 140, 350, and 875ng/kg/week for 29 weeks. Serum was collected and proteomic analysis was performed using automated Bruker Daltonics ClinProt with matrix-assisted laser desorption/ionization time-of-flight mass spectrometer. One peptide at 1740.89 was found to be significantly decreased and further identified with nano LC-MS/MS system. The MS BLAST homology search engine reported the peptide to be a partial sequence of fibrinopeptide A. Liver fatty degeneration and necrosis were assessed by hematoxylin and eosin staining. Liver fatty degeneration and necrosis were both found to be significantly increased after TCDD exposure. Levels of fibrinopeptide A were significantly correlated with liver fatty degeneration and necrosis.
Copyright © 2011 Elsevier B.V. All rights reserved.
Radionuclide Therapy in Neuroendocrine Tumours: A Systematic Review.
Source
Department of Nuclear Medicine, Hamilton Health Sciences & St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
Abstract
The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be considered. No strong evidence exists to support that one therapeutic radiopharmaceutical is more effective than others. Well-designed and good-quality randomised controlled trials are required on this research topic.
Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Pepitome: evaluating improved spectral library search for identification complementarity and quality assessment.
Abstract
Spectral libraries have emerged as a viable alternative to protein sequence databases for peptide identification. These libraries contain previously detected peptide sequences and their corresponding tandem mass spectra (MS/MS). Searchengines can then identify peptides by comparing experimental MS/MS scans to those in the library. Many of these algorithms employ the dot product score for measuring the quality of a spectrum-spectrum match (SSM). This scoring system does not offer a clear statistical interpretation and ignores fragment ion m/z discrepancies in the scoring. We developed a new spectral library search engine, Pepitome, which employs statistical systems for scoring SSMs. Pepitome outperformed the leading library search tool, SpectraST, when analyzing data sets acquired on three different mass spectrometry platforms. We characterized the reliability of spectral library searches by confirming shotgun proteomics identifications through RNA-Seq data. Applying spectral library and database searches on the same sample revealed their complementary nature. Pepitome identifications enabled the automation of quality analysis and quality control (QA/QC) for shotgun proteomics data acquisition pipelines.
BuildSummary: Using group-based approach to improve the sensitivity ofpeptide/protein identification in shotgun proteomics.
Abstract
The target-decoy database search strategy is widely accepted as a standard method for estimating the false discovery rate (FDR) of peptide identification, based on which peptide-spectrum matches (PSMs) from the target database are filtered. To improve the sensitivity of protein identification given a fixed accuracy (frequently defined by a protein FDR threshold), a post-processing procedure is often used that integrates results from different peptide search engines that had assayed the same dataset. In this work, we show that PSMs that are grouped by the precursor charge, the number of missed internal cleavage sites, the modification state, the numbers of protease termini and the proteins grouped by their unique peptide count should be filtered separately according to the given FDR. We also develop an iterative procedure to filter the PSMs and proteins simultaneously, according to the given FDR. Finally, we present a general framework to integrate the results from different peptide search engines using the same FDR threshold. Our method was tested with several shotgun proteomics datasets that were acquired by multiple LC/MS instruments from two different biological samples. The results showed a satisfactory performance. We implemented the method in a user-friendly software package called BuildSummary, which can be downloaded for free from http://www.proteomics.ac.cn/software/proteomicstools/index.htm as part of the software suite ProteomicsTools.
GuiTope: An Application for Mapping Random-Sequence Peptides to Protein Sequences.
Abstract
ABSTRACT:
BACKGROUND:
Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability tosearch a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task.
RESULTS:
GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the underlying amino acid frequency in the peptide library, which often differs significantly from the frequencies assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores to calculate statistical significance.
CONCLUSIONS:
GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The latest version of the software available as an executable (for PC) at www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.
Biomonitors of cardiac injury and performance: B-type natriuretic peptide and troponin as monitors of hemodynamics and oxygen transport balance.
Source
Children's Hospital of Orange County, Orange, CA, USA.
Abstract
Serum biomarkers, such as B-type natriuretic peptide and troponin, are frequently measured in the cardiac intensive care unit. A review of the evidence supporting monitoring of these biomarkers is presented.
DESIGN:
A search of MEDLINE, PubMed, and the Cochrane Database was conducted to find literature regarding the use of B-type natriuretic peptide and troponin in the cardiac intensive care setting. Adult and pediatric data were considered.
RESULTS AND CONCLUSION:
Both B-type natriuretic peptide and troponin have demonstrated utility in the intensive care setting but there is no conclusive evidence at this time that either biomarker can be used to guide inpatient management of children with cardiac disease. Although B-type natriuretic peptide and troponin concentrations can alert clinicians to myocardial stress, injury, or hemodynamic alterations, the levels can also be elevated in a variety of clinical scenarios, including sepsis. Observational studies have demonstrated that perioperative measurement of these biomarkers can predict postoperative mortality and complications. RECOMMENDATION AND
LEVEL OF EVIDENCE:
(class IIb, level of evidence B): The use of B-type natriuretic peptide and/or troponin measurements in the evaluation of hemodynamics and postoperative outcome in pediatric cardiac patients may be beneficial.
Modulation of matrix mineralization by Vwc2-like protein and its novel splicing isoforms.
Source
Department of Periodontology and Oral Biology, Boston University, Henry M. Goldman School of Dental Medicine, 700 Albany Street, Boston, MA 02118, USA.
Abstract
In search of new cysteine knot protein (CKP) family members, we found a novel gene called von Willebrand factor C domain-containing protein 2-like (Vwc2l, also known as Brorin-like) and its transcript variants (Vwc2l-1, Vwc2l-2 and Vwc2l-3). Based on the deduced amino acid sequence, Vwc2l-1 has a signal peptide and 2 cysteine-rich (CR) domains, while Vwc2l-2 lacks a part of 2nd CR domain and Vwc2l-3 both CR domains. Although it has been reported that the expression of Brorin-like was predominantly observed in brain, we found that Vwc2l transcript variants were detected in more ubiquitous tissues. In osteoblasts, the induction of Vwc2l expression was observed at matrix mineralization stage. When Vwc2l was stably transfected into osteoblasts, the matrix mineralization was markedly accelerated in Vwc2l-expressing clones compared to that in the control, indicating the modulatory effect of Vwc2l protein on osteoblastic cell function. The mechanistic insight of Vwc2l-modulation was further investigated and we found that the expression of Osterix, one of the key osteogenic markers, was significantly increased by addition of all Vwc2l isoform proteins. Taken together, Vwc2l is a novel secreted protein that promotes matrix mineralization by modulating Osterix expression likely through TGF-β superfamily growth factor signaling pathway. Our data may provide mechanistic insights into the biological functions of this novel CKP member in bone and further suggest a novel approach to enhance osteoblast function, which enables to accerelate bone formation, regeneration and healing.
Copyright © 2011. Published by Elsevier Inc.
Structures of peptide agonists for human protease activated receptor 2.
Source
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Abstract
Protease activated receptor 2 (PAR2) is an unusual G-protein coupled receptor in being self-activated, after pruning of the N-terminus by serine proteases like trypsin and tryptase. Short synthetic peptides corresponding to the newly exposed N-terminal hexapeptide sequence also activate PAR2 on immunoinflammatory, cancer and many normal cell types. (1)H nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy were used here to search for structural clues to activating mechanisms of the hexapeptide agonists SLIGRL (rat), SLIGKV (human) and the peptidomimetic analogue, 2-furoyl-LIGRLO. Either with a free or acetyl capped N-terminus, these agonist peptidesdisplay significant propensity in aprotic (DMSO) or lipidic (water-SDS) solvents for turn-like conformations, which are predicted to be receptor-binding conformations in the transmembrane or loops region of PAR2. These motifs may be valuable for the design of small molecule PAR2 agonists and antagonists as prospective new drugs for regulating inflammatory and proliferative diseases.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Exogenous glucagon-like Peptide-1 for hyperglycemia in critically ill patients.
Source
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI.
Abstract
OBJECTIVE:
To review literature evaluating the safety and efficacy of exogenous glucagon-like peptide-1 (GLP-1) for hyperglycemia in critically ill patients.
DATA SOURCES:
PubMed was queried (inception to September 3, 2011), using the search term glucagon-likepeptide-1. The search was limited to studies published in English and conducted in humans. Regular and late-breaking abstracts from the American Diabetes Association Scientific Sessions in 2009 and 2010 were also searched using the same search term.
STUDY SELECTION AND DATA EXTRACTION:
All abstracts were screened for eligibility, which consisted of studies reporting the effects of intravenous GLP-1 administration on glycemic control in critically ill patients. Data extracted from eligible trials included study and population characteristics, measures of glycemic efficacy, and safety.
DATA SYNTHESIS:
Our search resulted in the identification of 2105 potentially relevant articles; of those, 7 were reviewed. All included publications evaluated the use of intravenous GLP-1 (1.2-3.6 pmol/kg/min) compared with insulin or placebo infused for 4.5-72 hours in critically ill patients. The majority (n = 4) of studies included only patients from a surgical intensive care setting, and 71% (n = 5) of trials included those with a history of diabetes. Relative to insulin or placebo, GLP-1 therapy effectively lowered blood glucose concentrations in all trials. Out of 81 total study participants receiving GLP-1, only 4 had documented hypoglycemia (<60 mg/dL), 4 reported nausea, and 2 experienced vomiting. No other serious adverse events were reported.
CONCLUSIONS:
All trials reviewed suggest that GLP-1 may be a promising agent for the management of hyperglycemia in critically ill patients, regardless of diabetes status. Additional studies in more heterogeneous intensive care settings comparing GLP-1 with insulin, the current standard of care, are necessary. These studies should evaluate long-term safety and effectiveness of GLP-1 therapy on morbidity and mortality outcomes in critically ill populations.
Novel biomarkers in diagnosing cardiac ischemia in the emergency department: A systematic review.
Source
Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Rescu, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND:
Novel biomarkers of myocardial ischemia and inflammatory processes have the potential to improve diagnostic accuracy of acute coronary syndrome (ACS) within a shorter time interval after symptom onset.
OBJECTIVE:
The objective was to review the recent literature and evaluate the evidence for use of novel biomarkers in diagnosing ACS in patients presenting with chest pain or symptoms suggestive of cardiac ischemia to the emergency department or chest pain unit.
METHODS:
A literature search was performed in MEDLINE, EMBASE, Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED for studies from 2004 to 2010. We used the inclusion criteria: (1) human subjects, (2) peer-reviewed articles, (3) enrolled patients with ACS, acute myocardial infarction or undifferentiated signs and symptoms suggestive of ACS, and (4) English language or translated manuscripts. Two reviewers conducted a hierarchical selection and assessment using a scale developed by the International Liaison Committee on Resuscitation.
RESULTS:
Out of a total 3194 citations, 58 articles evaluating 37 novel biomarkers were included for final review. Forty-one studies did not support the use of their respective biomarkers. Seventeen studies supported the use of 5 biomarkers, particularly when combined with cardiac-specific troponin: heart fatty acid-binding protein, ischemia-modified albumin, B-type natriuretic peptide, copeptin, and matrix metalloproteinase-9.
CONCLUSION:
In patients presenting to the emergency department with chest pain or symptoms suggestive of cardiac ischemia, there is inadequate evidence to suggest the routine testing of novel biomarkers in isolation. However, several novel biomarkers have the potential to improve the sensitivity of diagnosing ACS when combined with cardiac-specific troponin.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Database independent proteomics analysis of the ostrich and human proteome.
Source
Biomolecular Mass Spectrometry and Proteomics Group, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Abstract
Mass spectrometry (MS)-based proteome analysis relies heavily on the presence of complete protein databases. Such a strategy is extremely powerful, albeit not adequate in the analysis of unpredicted postgenome events, such as posttranslational modifications, which exponentially increase the search space. Therefore, it is of interest to explore "database-free" approaches. Here, we sampled the ostrich and human proteomes with a method facilitating de novo sequencing, utilizing the protease Lys-N in combination with electron transfer dissociation. By implementing several validation steps, including the combined use of collision-induced dissociation/electron transfer dissociation data and a cross-validation with conventional database search strategies, we identified approximately 2,500 unique de novo peptidesequences from the ostrich sample with over 900 peptides generating full backbone sequence coverage. This dataset allowed the appropriate positioning of ostrich in the evolutionary tree. The described database-free sequencing approach is generically applicable and has great potential in important proteomics applications such as in the analysis of variable parts of endogenous antibodies or proteins modified by a plethora of complex posttranslational modifications.
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