Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage

OBJECTIVE: To test whether there is undersulfation of chondroitin sulfate in osteoarthritic bovine articular cartilage to support the hypothesis that sulfate deficiency is involved with the development of osteoarthritis. METHODS: Cartilage samples from bovine patellae (n = 32) were divided into 3 groups based on their osteoarthritic progression, as assessed by modified Mankin score. Uronic acid contents of the samples were determined. Fragmentation of the proteoglycans due to proteolytic processing was estimated with agarose gel electrophoresis. The molar ratios of chondroitin sulfate isoforms in the extracted proteoglycans were determined with fluorophore-assisted carbohydrate electrophoresis. RESULTS: Loss of proteoglycans and accumulation of tissue water was evident in groups II and III, and progressive OA increased heterogeneity of aggrecan population in groups II and III. Importantly, the molar ratio of nonsulfated disaccharide was decreased in the osteoarthritic articular cartilage. CONCLUSION: The structure of chondroitin sulfate in degenerated bovine cartilage did not support the hypothesis that sulfate depletion is present in osteoarthritic joint.     

Nosocomial urinary tract infection in the intensive care unit: when should Pseudomonas aeruginosa be suspected? Experience of the French national surveillance of nosocomial infections in the intensive care unit,Rea-Raisin

Individual and ward risk factors for P. aeruginosa-induced urinary tract infection in the case of nosocomial urinary tract infection in the intensive care unit were determined with hierarchical (multilevel) logistic regression. The 2004-2006 prospective French national intensive care unit nosocomial infection surveillance dataset was used and 3252 patients with urinary tract infection were included; 16% were infected by P. aeruginosa. Individual risk factors were male sex, duration of stay, antibiotics at admission and transfer from another intensive care unit. Ward risk factors were patient turnover and incidence of P. aeruginosa-infected patients.     

Characterization of enzymatically induced degradation of articular cartilage using high frequency ultrasound

Ultrasound may provide a quantitative technique for the characterization of cartilage changes typical of early osteoarthrosis. In this study, specific changes in bovine articular cartilage were induced using collagenase and chondroitinase ABC, enzymes that selectively degrade collagen fibril network and digest proteoglycans, respectively. Changes in cartilage structure and properties were quantified using high frequency ultrasound, microscopic analyses and mechanical indentation tests. The ultrasound reflection coefficient of the physiological saline-cartilage interface (R1) decreased significantly (-96.4%, p < 0.01) in the collagenase digested cartilage compared to controls. Also a significantly lower ultrasound velocity (-6.2%, p < 0.01) was revealed after collagenase digestion. After chondroitinase ABC digestion, a new acoustic interface at the depth of the enzyme penetration front was detected. Cartilage thickness, as determined with ultrasound, showed a high, linear correlation (R = 0.943, n = 60, average difference 0.073 mm (4.0%)) with the thickness measured by the needle-probe method. Both enzymes induced a significant decrease in the Young's modulus of cartilage (p < 0.01). Our results indicate that high frequency ultrasound provides a sensitive technique for the analysis of cartilage structure and properties. Possibly ultrasound may be utilized in vivo as a quantitative probe during arthroscopy.     

Collagenase-induced changes in articular cartilage as detected by electron-microscopic stereology,quantitative polarized light microscopy and biochemical assays

The purpose of this study was to compare the ability of electron-microscopic (EM) stereology with quantitative polarized light microscopy (PLM) and biochemical collagen (hydroxyproline) and crosslink (pyridinoline) analyses to detect changes in the superficial collagen network of bovine articular cartilage after digestion in vitro with purified bacterial (Clostridium histolyticum) collagenase (30 U/ml) for 24 and 48 h. Collagen volume (V(V)) and surface (S(V)) densities of the uppermost third of the superficial zone were estimated indirectly from zonal isotropic uniform random sections using collagen length density (L(V)) and average collagen fibril diameter, or its average second power. Collagenase digestion caused a significant decrease in fibril diameter (64 to 62%), V(V) (89 to 95%) and S(V) (64 to 86%) after incubation for 24 and 48 h. Collagen L(V) remained unchanged after 24 h incubation but decreased 63% after 48 h. Collagen concentration per dry weight, assayed biochemically from the whole superficial zone, decreased also significantly (29 to 60%) after 24 and 48 h digestions, respectively. The pyridinoline concentration per dry weight of the superficial zone decreased (31 to 57%) whereas the pyridinoline concentration per collagen remained unchanged. PLM revealed that the birefringence of the uppermost third of the superficial zone was decreased by 36% after digestion for 24 h though the total birefringence of the whole zone was not reduced. However, after 48 h, the birefringence of the whole superficial zone was significantly reduced (76%). All of the techniques compared in this study could detect collagen network degradation in bovine articular cartilage but the EM stereological technique was more sensitive at detecting the changes than PLM or biochemical assays.     

Mesoporous silicon in drug delivery applications

During the last few years, a number of interesting drug delivery applications of mesoporous materials have been demonstrated. Mesoporous silicon has many important properties advantageous to drug delivery applications. The small size of the pores confines the space of a drug and engages the effects of surface interactions of the drug molecules and the pore wall. The size of the pores and the surface chemistry of the pore walls may be easily changed and controlled. Depending on the size and the surface chemistry of the pores, increased or sustained release of the loaded drug can be obtained. Drug loading from a solution at room temperature enables the use of porous silicon (PSi) also with sensitive therapeutic compounds susceptible to degradation, like peptides and proteins. This article reviews the fabrication and chemical modifications of PSi for biomedical applications, and also the potential advantages of PSi in drug delivery.