Synthetic overlapping oligosaccharide fragments ofThe resulting antibodies were then tested for Pn14PS specificity and for their capacity to promote the phagocytosis of S. pneumoniae type 14 bacteria. Earlier studies have reported that the oligosaccharide corresponding to one structural repeating unit of Pn14PS, i.e., Gal-Glc-(Gal-)GlcNAc, induces a specific antibody response to Pn14PS. The broader study described here, which evaluated 16 oligosaccharides, showed that the branched trisaccharide element Glc-(Gal-)GlcNAc is essential in inducing Pn14PS-specific antibodies and that the neighboring galactose unit at the nonreducing end contributes clearly to the immunogenicity of the epitope. Only the oligosaccharide conjugates that produce antibodies recognizing Pn14PS were capable of promoting the phagocytosis of S. pneumoniae type 14. In conclusion, the branched tetrasaccharide Gal-Glc-(Gal-)GlcNAc may be a serious candidate for a synthetic oligosaccharide conjugate vaccine against infections caused by S. pneumoniae type 14.

A stable PEG-PE nanomicellar formulation of quercetin was developed with enhanced peroral anticancer activity and no apparent toxicity to the intestinal epithelium.

Cryptococcal capsular Ags induce the production of proinflammatory cytokines in patients with cryptococcal meningitis. Despite this, their cerebrospinal fluid typically contains few neutrophils. Capsular glucuronoxylomannan is generally considered to mediate the inhibition of neutrophil extravasation. In the current study, culture supernatant harvested from the nonglucuronoxylomannan-producing strain CAP67 was found to be as potent as supernatant from wild-type strains in preventing migration. We identified capsular mannoprotein (MP)-4 as the causative agent. Purified MP-4 inhibited migration of neutrophils toward platelet-activating factor, IL-8, and fMLP, probably via a mechanism involving chemoattractant receptor cross-desensitization, as suggested by its direct chemotactic activity. Supporting this hypothesis, MP-4 elicited Ca2+ transients that were inhibited by preincubation with either fMLP, IL-8, or C5a, but not platelet-activating factor, and vice versa. Moreover, MP-4 strongly decreased the neutrophil surface expression of L-selectin and induced shedding of TNF receptors p55/p75, whereas CD11b/18 increased. Finally, MP-4 was clearly detectable in both serum and cerebrospinal fluid of patients suffering from cryptococcal meningitis. These findings identify MP-4 as a novel capsular Ag prematurely activating neutrophils and desensitizing them toward a chemoattractant challenge.

BackgroundAmpicillin-resistant Enterococcus faecium (ARE) has emerged as a nosocomial pathogen. Here, we quantified ARE carriage in different community sources and determined genetic relatedness with hospital ARE.Methods and ResultsARE was recovered from rectal swabs of 24 of 79 (30%) dogs, 11 of 85 (13%) cats and 0 of 42 horses and from 3 of 40 (8%) faecal samples of non-hospitalized humans receiving amoxicillin. Multi-locus Sequence Typing revealed 21 sequence types (STs), including 5 STs frequently associated with hospital-acquired infections. Genes previously found to be enriched in hospital ARE, such as IS16, orf903, orf905, orf907, were highly prevalent in community ARE (≥79%), while genes with a proposed role in pathogenesis, such as esp, hyl and ecbA, were found rarely (≤5%) in community isolates. Comparative genome analysis of 2 representative dog isolates revealed that the dog strain of ST192 was evolutionarily closely linked to two previously sequenced hospital ARE, but had, based on gene content, more genes in common with the other, evolutionarily more distantly related, dog strain (ST266).ConclusionARE were detected in dogs, cats and sporadically in healthy humans, with evolutionary linkage to hospital ARE. Yet, their accessory genome has diversified, probably as a result of niche adaptation.

Objective To investigate peritoneal defense during icodextrin use in continuous cyclic peritoneal dialysis (CCPD). Design In an open, prospective, 2-year follow-up study, CCPD patients were randomized to either glucose (Glu) or icodextrin (Ico) for their long daytime dwell. Setting University hospital and teaching hospital. Patients Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years, those who had peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients (19 Glu, 19 Ico) started the study. The median follow-up was 16 and 17 months for Glu and Ico respectively (range 0.5 – 25 months and 5 – 25 months, respectively). Outcome Measures Peritoneal defense characteristics and peritoneal dialysis-related infections were recorded every 3 months. Results Total peritoneal white cell count tended to decrease over time in both groups. After 1 year, absolute numbers and percentages of effluent peritoneal macrophages (PMΦs) were significantly higher in Ico than in Glu patients; this difference in the percentage persisted after 2 years. Percentage of mesothelial cells increased over time in Ico patients. The phagocytic capacity of PMΦs decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci ( p = 0.05) and a significant difference for Escherichia coli ( p < 0.05) phagocytosis in favor of Ico patients. PMΦ oxidative metabolism remained stable over time without a difference between the groups. PMΦ cytokine production and effluent opsonic capacity also remained stable over time. Finally, 16 peritonitis episodes in Glu and 14 in Ico patients occurred. Glucose patients had 37 and Ico patients 32 exit-site infections during the study. Conclusion CCPD patients using Ico did equally as well as Glu-treated patients with respect to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, Ico-treated patients did better.