Antiadhesive Compounds Research Articles

The Use of Carbohydrate Microarrays to Study Carbohydrate-Cell Interactions and to Detect Pathogens

The use of carbohydrate microarrays to investigate the carbohydrate binding specificities of bacteria, to detect pathogens, and to screen antiadhesion therapeutics is reported. This system is ideal for whole-cell applications because microarrays present carbohydrate ligands in a manner that mimics interactions at cell-cell interfaces. Other advantages include assay miniaturization, since minimal amounts (approximately picomoles) of a ligand are required to observe binding, and high throughput, since thousands of compounds can be placed on an array and analyzed in parallel. Pathogen detection experiments can be completed in complex mixtures of cells or protein using the known carbohydrate binding epitopes of the pathogens in question. The nondestructive nature of the arrays allows the pathogen to be harvested and tested for antibacterial susceptibility. These investigations allow microarray-based screening of biological samples for contaminants and combinatorial libraries for antiadhesion therapeutics.

Oligosaccharide receptor mimics inhibit Legionella pneumophila attachment to human respiratory epithelial cells

Legionnaire's disease is caused by the intracellular pathogen Legionella pneumophila, presenting as an acute pneumonia. Attachment is the key step during infection, often relying on an interaction between host cell oligosaccharides and bacterial adhesins. Inhibition of this interaction by receptor mimics offers possible novel therapeutic treatments. L. pneumophila attachment to the A549 cell line was significantly reduced by treatment with tunicamycin (73.6%) and sodium metaperiodate (63.7%). This indicates the importance of cell surface oligosaccharide chains in adhesion. A number of putative anti-adhesion compounds inhibited attachment to the A549 and U937 cell lines. The most inhibitory compounds were polymeric saccharides, GalNAcβ1-4Gal, Galβ1-4GlcNAc and para-nitrophenol. These compounds inhibited adhesion to a range of human respiratory cell lines, including nasal epithelial, bronchial epithelial and alveolar epithelial cell lines and the human monocytic cell line, U937. Some eukaryotic receptors for L. pneumophila were determined to be the glycolipids, asialo-GM1 and asialo-GM2 that contain the inhibitory saccharide moiety, GalNAcβ1-4Gal. The identified compounds have the potential to be used as novel treatments for Legionnaire's disease.

Adhesion of endometrial cells labeled with 111Indium-tropolonate to peritoneum: a novel in vitro model to study endometriosis

Objective To evaluate, in a new original in vitro assay, putative factors that could modulate the adhesion of endometrial cells to peritoneum. Design Prospective, controlled in vitro study. Setting Academic research laboratory. Patient(s) Fourteen nonmenopausal women undergoing hysterectomy or laparoscopy for benign gynecologic indication. Intervention(s) Endometrial cells obtained from women with regular cycles without endometriosis were labeled with 111Indium and confronted in vitro with mouse peritoneum in the presence of various cytokines and/or antiadhesive compounds. Main outcome measure(s) Radioactivity in 111Indium-labeled endometrial cells. Result(s) The adhesion of human endometrial cells to mouse peritoneum was increased by treatment with pro-inflammatory cytokines (interleukin IL-1β, IL-6, TNF α, TGF-β1). Whereas heparan sulfate had no effect on cell adhesion, a gel of ferric hyaluronate (Intergel) was able to counteract the pro-adhesive effect of cytokines. Interestingly, the pretreatment of peritoneum with cytokines, 24 hours before cell seeding in the presence of the ferric hyaluronate gel, restored the cytokine-promoting effect on cell adhesion. Conclusion(s) Proinflammatory cytokines promote the in vitro peritoneal adhesion of endometrial cells. An antiadhesive hyaluronate gel used in clinics decreases the adhesion in a dose-dependent manner and reduces cytokine bioavailability.

Treatment of acute otitis media with an antiadhesive oligosaccharide: a randomised, double-blind, placebo-controlled trial

Antiadhesive compounds are promising candidates for prevention or treatment of infections. We have investigated the efficacy of such an agent, 3'-sialyllacto-N-neotetraose (NE-1530), given intranasally for prophylaxis of acute otitis media and for effect on nasopharyngeal carriage of bacteria. We did a randomised, double-blind placebo-controlled study at one study site. 507 healthy children were randomly assigned either NE-1530 (n=254) or placebo (253) as intranasal sprays twice daily during 3 months. The children were examined by the study physicians once a month and during illness. Treatment efficacy was estimated from Cox proportional hazards model. A sample of nasopharyngeal secretion was taken at every visit for culture of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Adverse events were recorded in study diaries. At least one event of acute otitis media was diagnosed in 108 (43%) of 254 children in the NE-1530 group and in 86 (34%) of 253 children in the placebo group. The efficacy of treatment was negative, -27% (95% CI -68 to 5; p=0.10). The nasopharyngeal carriage of S pneumoniae, H. influenzae, and M. catarrhalis was not affected by treatment, and the adverse event profiles were almost identical for NE-1530 and placebo. NE-1530 did not have a beneficial effect on the occurrence of acute otitis media or on the nasopharyngeal carriage of bacteria in children.

Opportunities for immune modulation in the spondyloarthropathies with special reference to gut inflammation.

The spondyloarthropathies (SpA) are a related group of disorders, characterized primarily by spondylitis, pauci-articular arthritis and enthesitis. The presence of subclinical gut inflammation in patients with SpA ranges from 25 to 75%, depending upon the type of SpA. Several data suggest that the association between gut inflammation and synovitis reflects an etiopathogenetic relationship, and that strategies which interfere with the gut inflammation may also modulate the synovitis. Here we review some standard as well as experimental drugs used in the treatment of patients with inflammatory bowel disease and discuss what is known about their effect on SpA-related locomotor manifestations. For the more experimental drugs, such as cytokines, anticytokines and anti-adhesion compounds, clinical trials in patients with SpA are still very scarce.

Weak Boundary Layers in Styrene-Butadiene Rubber

Abstract In this paper two kinds of weak boundary layers (WBL) in synthetic vulcanized styrene-butadiene rubber are described. i) WBL produced by the presence of antiadhesion compounds of the rubber formulation (zinc stearate, microcrystalline paraffin wax). These WBL cannot be effectively removed by solvent wiping, whether followed by washing with an ethanol/water mix or not. Although this treatment allowed a significant removal of zinc stearate, the paraffin wax concentration on the surface was not greatly reduced, thus, poor adhesion of rubber was obtained. Chlorination with small amounts of ethyl acetate (EA) solutions of trichloro isocyanuric acid (0.5–5 wt% TCI/EA) and/or an extended halogenation treatment increased the adhesion strength and effectively eliminated the zinc stearate from the rubber surface. If an additional heat treatment (50°C/24h) of the chlorinated rubber was also carried out, the WBL was more effectively eliminated and the resulting adhesion was independent of the amount of chlor...