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Biomedical subjects

Peter A Cadieux

Publications and source records attributed to Peter A Cadieux.

10 recordsLinked to original sources

Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius.

Streptococcus salivarius strains commonly produce bacteriocins as putative anti-competitor or signalling molecules. Here we report that bacteriocin production by the oral probiotic strain S. salivarius K12 is encoded by a large (ca. 190 kb) plasmid. Oral cavity transmission of the plasmid from strain K12 to a plasmid-negative variant of this bacterium was demonstrated in two subjects. Tests of additional S. salivarius strains showed large (up to ca. 220 kb) plasmids present in bacteriocin-producing isolates. Various combinations (up to 3 per plasmid) of loci encoding the known streptococcal lantibiotics salivaricin A, salivaricin B, streptin and SA-FF22 were localised to these plasmids. Since all bacteriocin-producing strains of S. salivarius tested to date appear to harbour plasmids, it appears that they may function as mobile repositories for bacteriocin loci, especially those of the lantibiotic class.

Bacterial Proteins↗

Triclosan loaded ureteral stents decrease proteus mirabilis 296 infection in a rabbit urinary tract infection model.

PURPOSE: Infection and encrustation remain major limitations of ureteral stent use and to our knowledge no device has completely overcome these obstacles to date. Triclosan is a biocide currently used in a plethora of consumer and medical products that has recently been loaded into a ureteral stent. Using a rabbit model of UTI we examined the effects of triclosan impregnated stent segments on the growth and survival of Proteus mirabilis, a uropathogen commonly associated with device related UTI and encrustation. MATERIALS AND METHODS: A total of 48 male New Zealand White rabbits were instilled transurethrally with 1 x 10(6) P. mirabilis 296. A stent curl from a triclosan eluting, Percuflex Plus or Optima ureteral stent was placed intravesically. Urine was cultured on days 1, 3 and 7. On day 7 the stents were assessed for encrustation and viable organisms, while the bladders were scored for the degree of inflammation. RESULTS: Throughout the study urine isolated from the triclosan group contained significantly fewer viable organisms than controls with 7 of 13 animals completely clearing the infection by day 7. Similarly 9 of 13 triclosan eluting stents showed no viable organisms upon recovery and the remaining 4 showed significantly fewer organisms than controls. Urine and stents in all controls were positive for P. mirabilis at all time points. Although there was no significant difference in encrustation among the groups, bladders harvested from the triclosan group demonstrated significantly less inflammation. CONCLUSIONS: Triclosan eluting stents greatly decreased P. mirabilis growth and survival in a rabbit UTI model compared to controls. These stents may prove useful for decreasing device related P. mirabilis UTIs.

Animals↗

In-vitro activity of triclosan-eluting ureteral stents against common bacterial uropathogens.

BACKGROUND AND PURPOSE: Ureteral stents are commonly used in urology today, but the biofilms that form on them within hours of placement may harbor bacteria that can result in infection or encrustation. Triclosan is an antimicrobial commonly used in consumer and medical products that inhibits bacterial fatty-acid synthesis. The bactericidal and bacteriostatic effect of a triclosan-eluting ureteral stent was tested against clinical isolates of common bacterial uropathogens in an in-vitro setting. MATERIALS AND METHODS: Triclosan eluted from a drug-loaded ureteral stent was suspended in artificial urine with bacterial pathogens (Escherichia coli C1214, Proteus mirabilis 296, Enterococcus faecalis 1131, Klebsiella pneumoniae 280, Staphylococcus aureus Newman, Pseudomonas aeruginosa AK1) to assess growth, virulence-promoter activity, and bacterial adherence to the stent. Generic stents were utilized as controls. RESULTS: Triclosan inhibited the growth of E. faecalis, K. pneumoniae, S. aureus, and P. mirabilis in a dose-dependent manner. Pseudomonas aeruginosa demonstrated significant resistance. Lower concentrations of triclosan downregulated E. coli virulence-factor promoters of outer membrane protein X and p-fimbriae. Triclosan stents had significantly fewer adherent viable bacteria than control stents. CONCLUSIONS: Triclosan-eluting ureteral stents inhibit the growth of common bacterial uropathogens and thus may reduce the incidence of urinary-tract infections and, potentially, encrustation. This drug-eluting stent provides both mechanical drainage of the upper urinary tract and local antibiosis.

Anti-Infective Agents, Local↗

Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS): a new proteomic urinary test for patients with urolithiasis.

SELDI-TOF-MS is a highly sensitive protein-analysis tool capable of detecting minute protein profile differences between biological samples. As proteins have been associated with urinary tract calculi, protein-based urinalysis may offer insights into their diagnosis. The purpose of this study was to evaluate SELDI-TOF-MS as a potential method for identifying urinary biomarkers of urolithiasis. Midstream sterile urine samples were obtained from 25 male patients with a confirmed diagnosis of urolithiasis (test group) and 25 male subjects with no known history of the disease (controls). Urinary levels of oxalate, total protein, albumin, and osteopontin were determined. Protein profiles were generated using SELDI-TOF-MS.SELDI-TOF-MS profiling revealed a relationship between protein peak intensities at 67 and 24 kDa that differed between the two groups. The ratio of p67:p24 was found to be less than 1.0 in all of the control samples (mean 0.26), while 18 out of 25 (72%) of the test group samples displayed a ratio greater than 1.0 (total group mean 4.75, P<0.001). Albumin, total protein, and oxalate levels were higher in the test group than the controls. Although SELDI-TOF-MS is not yet in widespread use in hospital and diagnostic laboratories, this system represents a promising new method for rapidly identifying patients with urolithiasis.

Albumins↗

Urinary tract biomaterials.

PURPOSE: As a result of endourological advances, biomaterials have become increasingly used within the urinary tract. This review article provides an update on the current status of urinary tract biomaterials, discussing issues of biocompatibility, biomaterials available for use, clinical applications and biomaterial related complications. Perspectives on future materials for use in the urinary tract are also provided. MATERIALS AND METHODS: We performed a comprehensive search of the peer reviewed literature on all aspects of biomaterials in the urinary tract using PubMed and MEDLINE. All pertinent articles were reviewed in detail. RESULTS: Any potential biomaterial must undergo rigorous physical and biocompatibility testing prior to its commercialization and use in humans. There are currently many different bulk materials and coatings available for the manufacturing of biomaterials, although the ideal material has yet to be discovered. For use in the urinary tract, biomaterials may be formed into devices, including ureteral and urethral stents, urethral catheters and percutaneous nephrostomy tubes. Despite significant advances in basic science research involving biocompatibility issues and biofilm formation, infection and encrustation remain associated with the use of biomaterials in the urinary tract and, therefore, limit their long-term indwelling time. CONCLUSIONS: Prosthetic devices formed from biomaterials will continue to be an essential tool in the practicing urologist's armamentarium. Ongoing research is essential to optimize biocompatibility and decrease biomaterial related complications such as infection and encrustation within the urinary tract. Future advances include biodegradables, novel coatings and tissue engineering.

Biocompatible Materials↗

Oxalate-degrading enzymes from Oxalobacter formigenes: a novel device coating to reduce urinary tract biomaterial-related encrustation.

BACKGROUND AND PURPOSE: The long-term placement of biomaterials within the urinary tract is limited by the development of encrustation. In a noninfected urinary environment, encrustation often results from the deposition of calcium oxalate on the biomaterial surface. There is an association between the absence of Oxalobacter formigenes, a commensal colonic bacterium capable of degrading oxalate, and calcium oxalate stone formation. This pilot study was designed to evaluate several oxalate-degrading enzymes produced by O. formigenes as a potential biomaterial coating to reduce urinary tract encrustation. MATERIALS AND METHODS: Circular silicone disks of 6-mm diameter were incubated for 48 hours in oxalylcoenzyme A decarboxylase (OXC), formyl-coenzyme A transferase (FRC), and coenzyme A, while control disks were incubated in distilled water. The adsorption of OXC and FRC was assessed using enhanced chemiluminescence (ECL) and atomic force microscopy (AFM). Coated and uncoated disks (20 of each) were implanted in the bladders of 40 female New Zealand White rabbits. After 30 days, the disks were recovered, and the degree of encrustation on the polymer surface was evaluated utilizing dry weight measurement, calcium atomic absorption spectroscopy (AAS), and scanning electron microscopy/energy-dispersive X-ray analysis (SEM/EDX). RESULTS: Both ECL and AFM demonstrated coating of the silicone disks with OXC and FRC. The mean dry weights of the coated and control disks following explantation were 0.591 +/- 0.438 g and 0.747 +/- 0.428 g, respectively (P = 0.307). The mean weight of calcium on the coated and control disks, as determined by AAS, was 154.1 +/- 96.25 mg and 258 +/- 181.35 mg, respectively (P = 0.008). CONCLUSIONS: The use of oxalate-degrading enzymes from O. formigenes to coat urinary biomaterials represents a novel paradigm to reduce biomaterial-related encrustation. Coating of silicone with oxalate-degrading enzymes from O. formigenes results in a modest reduction in encrustation with no apparent toxicity. Further studies are warranted.

Animals↗

Swarming of Proteus mirabilis over ureteral stents: a comparative assessment.

BACKGROUND AND PURPOSE: Encrustation on indwelling ureteral stents is commonly related to the presence of urease-producing bacteria that elevate the pH of the urine through the hydrolysis of urea, resulting in the precipitation of calcium and magnesium salts. Using a model previously shown to measure accurately the ability of Proteus mirabilis to swarm over catheter surfaces (Eur J Clin Microbiol Infect Dis 1999;18:206), we investigated the ability of this organism to swarm over three ureteral stents with potential encrustation-resistance properties. MATERIALS AND METHODS: Three commercially available ureteral stents were selected for evaluation: a low surface-energy stent, a hydrogel-coated stent, and a silicone stent. Ten-microliter aliquots of a 4-hour culture of P. mirabilis 296 in Trypticase soya (TSA) broth was inoculated 5 mm from a 1-cm channel cut out from TSA plates. Ten-millimeter stent sections were placed as bridges across the central channel adjacent to the inocula. Time to pathogen crossing was measured. RESULTS: The mean time (+/- SD) to pathogen migration across the three test materials was 15.9 +/- 6.1, 19.8 +/- 9.5, and 29.7 +/- 14.3 hours for the low surface-energy, hydrogel-coated, and silicone stents, respectively. Statistical analysis revealed significant differences between the crossing times of the low surface-energy (P = 0.001) and hydrogel-coated (P = 0.034) stents compared with silicone but not between the low surface-energy and hydrogel-coated stents (P = 0.387). CONCLUSION: Migration of P. mirabilis 296 across silicone stents was significantly reduced compared with low surface-energy and hydrogel-coated stents. These findings suggest that P. mirabilis may have a lower affinity for silicone stents, which may translate into a reduced risk of infection with P. mirabilis and associated stent encrustation.

Equipment Contamination↗

Improved understanding of the bacterial vaginal microbiota of women before and after probiotic instillation.

The vaginal bacterial microbiota of 19 premenopausal women was examined by PCR-denaturing gradient gel electrophoresis (DGGE) and sequencing of the V2-V3 region of the 16S rRNA gene. Ten of the women were studied further to investigate the effect and persistence of vaginally inserted capsules containing viable lactobacilli. PCR-DGGE indicated that most subjects had a microbiota represented by one to three dominant DNA fragments. Analysis of these fragments revealed that 79% of the women possessed sequences with high levels of similarity to Lactobacillus species sequences. Sequences homologous to Lactobacillus iners sequences were the most common and were detected in 42% of the women tested. Alteration of the vaginal microbiota could be detected by PCR-DGGE in several women after the instillation of lactobacilli. Additionally, randomly amplified polymorphic DNA analysis of lactobacilli isolated from selective media demonstrated that the exogenous strains could be detected for up to 21 days in some subjects. This study demonstrates that non-culture-based techniques, such as PCR-DGGE, are useful adjuncts for studies of the vaginal microbiota.

Adult↗

Rat PSP94 inhibits the growth and viability of the rat adenocarcinoma cell line PAIII in vitro.

Previous studies have shown that human PSP94 can inhibit the growth of prostate cancer cells both in vitro and in vivo. To further validate this potential and investigate the protein within a homologous setting, we examined the effects of rat PSP94 on the growth of the rat prostate adenocarcinoma cell line PAIII in vitro. To generate rat PSP94, we used both a plasmid-based expression system and a recombinant rat PSP molecule. Rat PSP was shown to inhibit the growth and survival of PAIII cells in a dose-dependent manner with > 90 percent reductions in both observed. TUNEL and Annexin-V assays confirmed PAIII cell death to be via apoptosis.

Adenocarcinoma↗