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1.  Elastase, α1-Proteinase Inhibitor, and Interleukin-8 in Children and Young Adults with End-Stage Kidney Disease Undergoing Continuous Ambulatory Peritoneal Dialysis 
Peritoneal dialysis is one of the main modality of treatment in end-stage kidney diseases (ESKD) in children. In our previous work in chronic kidney disease patients, in pre-dialyzed period and on hemodialysis, the neutrophils were highly activated. The aim of this study was to assess an inflammatory condition and neutrophil activation in ESKD patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Thirteen CAPD patients without infection, both sexes, aged 2.5–24 years, and group of healthy subjects (C) were studied. For comparative purposes the conservatively treated (CT) group of ESKD patients was included. Neutrophil elastase in complex with α1-proteinase inhibitor (NE-α1PI; ELISA), α1-proteinase inhibitor (α1PI; radial immunodiffusion) and interleukin-8 (IL-8; ELISA) were measured in the blood samples from CAPD, CT, and C group and in the peritoneal dialysate fluid (PDF) samples of patients on CAPD. A significantly increased plasma NE-α1PI levels (median 176.5 μg/L, range 85.2–373.2 μg/L; p < 0.00005), serum IL-8 (median 18.6 pg/mL, range 15.73–35.28 pg/mL; p < 0.05), and slightly decreased serum α1PI (median 1,540 mg/L, range 1,270–1,955; p ≤ 0.05) compared to the control groups were found. There were no significant differences of analyzed parameters between CAPD and CT patients. The concentration ratio of NE-α1PI, α1PI and IL-8 in blood/PDF was 29.97, 8.24, and 4.48, respectively. There were significantly positive correlations between serum and PDF concentration of α1PI and IL-8 (r = 0.613, p < 0.05; r = 0.59; p < 0.005, respectively). The results of our study demonstrate that neutrophils are highly activated in non-infected CAPD patients. The pivotal marker of this activation is NE-α1PI. It may contribute to chronic inflammation and tissues injury.
PMCID: PMC4024125  PMID: 24292797
Neutrophil elastase; α1-Proteinase inhibitor; Interleukin-8; End-stage kidney diseases; Continuous ambulatory peritoneal dialysis
2.  Characterising the biology of novel lytic bacteriophages infecting multidrug resistant Klebsiella pneumoniae 
Virology Journal  2013;10:100.
Members of the genus Klebsiella are among the leading microbial pathogens associated with nosocomial infection. The increased incidence of antimicrobial resistance in these species has propelled the need for alternate/combination therapeutic regimens to aid clinical treatment. Bacteriophage therapy forms one of these alternate strategies.
Electron microscopy, burst size, host range, sensitivity of phage particles to temperature, chloroform, pH, and restriction digestion of phage DNA were used to characterize Klebsiella phages.
Results and conclusions
Of the 32 isolated phages eight belonged to the family Myoviridae, eight to the Siphoviridae whilst the remaining 16 belonged to the Podoviridae. The host range of these phages was characterised against 254 clinical Enterobacteriaceae strains including multidrug resistant Klebsiella isolates producing extended-spectrum beta-lactamases (ESBLs). Based on their lytic potential, six of the phages were further characterised for burst size, physicochemical properties and sensitivity to restriction endonuclease digestion. In addition, five were fully sequenced. Multiple phage-encoded host resistance mechanisms were identified. The Siphoviridae phage genomes (KP16 and KP36) contained low numbers of host restriction sites similar to the strategy found in T7-like phages (KP32). In addition, phage KP36 encoded its own DNA adenine methyltransferase. The φKMV-like KP34 phage was sensitive to all endonucleases used in this study. Dam methylation of KP34 DNA was detected although this was in the absence of an identifiable phage encoded methyltransferase. The Myoviridae phages KP15 and KP27 both carried Dam and Dcm methyltransferase genes and other anti-restriction mechanisms elucidated in previous studies. No other anti-restriction mechanisms were found, e.g. atypical nucleotides (hmC or glucosyl hmC), although Myoviridae phage KP27 encodes an unknown anti-restriction mechanism that needs further investigation.
PMCID: PMC3620542  PMID: 23537199
Bacteriophage; Klebsiella spp.; Multidrug resistance; Restriction endonuclease patterns; Myoviridae; Siphoviridae; Podoviridae
3.  Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy 
Glycoconjugate Journal  2012;30(6):599-608.
The sugar moiety of IgA is known to provide a link between the innate and adaptive immune systems. Terminally located glycotopes on IgA are potential ligands engaged in the interactions which may modulate the biological activities of IgA. In the present work the expressions of Maackia amurensis (MAA), Sambucus nigra (SNA), Lens culinaris (LCA), Tetragonolobus purpureus (LTA), and Ulex europaeus (UEA) reactive glycotopes on maternal plasma and amniotic IgA were evaluated in relation to the progression of a normal human pregnancy, from the 2nd trimester, throughout the 3rd trimester, perinatal period, post-date pregnancy and delivery, by lectin-IgA-ELISA, using specific biotinylated lectins. The amniotic and maternal plasma IgA concentrations and a degree of SNA and LCA reactivity of maternal plasma IgA were almost unaltered during the normal pregnancy. The amniotic IgA from the 2nd trimester was decorated by MAA-, SNA-reactive and LCA-, LTA-, and UEA-reactive glycotopes. At the turn of the 2nd and 3rd trimesters the expression of MAA-, SNA-, LTA-, and UEA-reactive glycotopes, except for LCA-reactive, increased and remained almost at unaltered levels throughout the perinatal period and delivery. However, in the post-date pregnancy the expression of LCA-, LTA-, and UEA-reactive and SNA-reactive glycotopes were significantly higher. The unique fucosylated and sialylated glycovariants of amniotic IgA associated with the progression of the normal pregnancy may illustrate a general importance of carbohydrate-lectin receptor interactions in the control and modulation of biological events to ensuring homeostasis during pregnancy, protection and well-being of fetus.
PMCID: PMC3717160  PMID: 23250795
Amniotic fluid; Fucosylation; Glycovariant; Glycotope; Immunoglobulin A; Lectin; Pregnancy; Sialylation
4.  Innate immune properties of selected human neuropeptides against Moraxella catarrhalis and nontypeable Haemophilus influenzae 
BMC Immunology  2012;13:24.
Considerable evidence supports the concept of active communication between the nervous and immune systems. One class of such communicators are the neuropeptides (NPs). Recent reports have highlighted the antimicrobial activity of neuropeptides, placing them among the integral components of innate immune defense. This study examined the action of four human neuropeptides: calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and somatostatin (SOM), which are accessible in the upper respiratory tract, against two human-specific respiratory pathogens. We studied: (i) neuropeptide-mediated direct antibacterial activity exerted against Moraxella catarrhalis and nontypeable Haemophilus influenzae, and (ii) indirect immunomodulatory role of these neuropeptides in the neutrophil-mediated phagocytosis of indicated pathogens.
We found that 100 micromolar concentrations of CGRP, NPY, SP, and SOM effectively permeabilized bacterial membranes and showed (except SOM) bactericidal activity against both pathogens. SOM acted only bacteriostatically. However the killing efficacy was dependent on the bactericidal assay used. The rank order of killing NP effect was: NPY ≥ CGRP > SP >> SOM and correlated with their potency to permeabilize bacterial membranes. The killing and permeabilization activity of the analyzed NPs showed significant correlation with several physicochemical properties and amino acid composition of the neuropeptides. M. catarrhalis was more sensitive to neuropeptides than nontypeable H. influenzae.
The immunomodulatory bimodal effect of physiological concentrations of CGRP, NPY, and SP on the phagocytic function of human neutrophils against M. catarrhalis and H. influenzae was observed both in the ingestion (pathogen uptake) and reactive oxygen species generation stages. This effect was also dependent on the distinct type of pathogen recognition (opsonic versus nonopsonic).
The present results indicate that neuropeptides such as CGRP, NPY, and SP can effectively participate in the direct and indirect elimination of human-specific respiratory pathogens. Because the studied NPs show both direct and indirect modulating antimicrobial potency, they seem to be important molecules involved in the innate host defense against M. catarrhalis and nontypeable H. influenzae.
PMCID: PMC3460729  PMID: 22551165
Neuropeptide Y; Substance P; CGRP; Somatostatin; Killing; Permeabilization; Phagocytosis; Immunomodulation; Moraxella catarrhalis; Haemophilus influenzae
5.  Isolation and characterisation of KP34—a novel φKMV-like bacteriophage for Klebsiella pneumoniae 
Bacteriophage KP34 is a novel virus belonging to the subfamily Autographivirinae lytic for extended-spectrum β-lactamase-producing Klebsiella pneumoniae strains. Its biological features, morphology, susceptibility to chemical and physical agents, burst size, host specificity and activity spectrum were determined. As a potential antibacterial agent used in therapy, KP34 molecular features including genome sequence and protein composition were examined. Phylogenetic analyses and clustering of KP34 phage genome sequences revealed its clear relationships with “phiKMV-like viruses”. Simultaneously, whole-genome analyses permitted clustering and classification of all phages, with completely sequenced genomes, belonging to the Podoviridae.
Electronic supplementary material
The online version of this article (doi:10.1007/s00253-011-3149-y) contains supplementary material, which is available to authorized users.
PMCID: PMC3082699  PMID: 21327407
φKMV-like bacteriophage; Genome; Klebsiella pneumoniae; Phage therapy; Podoviridae; phiKMV-like viruses
6.  Direct and Indirect Antimicrobial Activities of Neuropeptides and their Therapeutic Potential 
Current Protein & Peptide Science  2012;13(8):723-738.
As global resistance to conventional antibiotics rises we need to develop new strategies to develop future novel therapeutics. In our quest to design novel anti-infectives and antimicrobials it is of interest to investigate host-pathogen interactions and learn from the complexity of host defense strategies that have evolved over millennia. A myriad of host defense molecules are now known to play a role in protection against human infection. However, the interaction between host and pathogen is recognized to be a multifaceted one, involving countless host proteins, including several families of peptides. The regulation of infection and inflammation by multiple peptide families may represent an evolutionary failsafe in terms of functional degeneracy and emphasizes the significance of host defense in survival. One such family is the neuropeptides (NPs), which are conventionally defined as peptide neurotransmitters but have recently been shown to be pleiotropic molecules that are integral components of the nervous and immune systems. In this review we address the antimicrobial and anti-infective effects of NPs both in vitro and in vivo and discuss their potential therapeutic usefulness in overcoming infectious diseases. With improved understanding of the efficacy of NPs, these molecules could become an important part of our arsenal of weapons in the treatment of infection and inflammation. It is envisaged that targeted therapy approaches that selectively exploit the anti-infective, antimicrobial and immunomodulatory properties of NPs could become useful adjuncts to our current therapeutic modalities.
PMCID: PMC3601409  PMID: 23305360
Neuropeptides; anti-infective action; antimicrobial action; immunomodulation; therapeutic potential.

Results 1-6 (6)