VEGF and its role in the early development of the long bone epiphysis.

In long bones of murine species, undisturbed development of the epiphysis depends on the generation of vascularized cartilage canals shortly after birth. Despite its importance, it is still under discussion how this event is exactly regulated. It was suggested previously that, following increased hypoxia in the epiphyseal core, angiogenic factors are expressed and hence stimulate the ingrowth of the vascularized canals. In the present study, we tested this model and examined the spatio-temporal distribution of two angiogenic molecules during early development in mice. In addition, we investigated the onset of cartilage hypertrophy and mineralization. Our results provide evidence that the vascular endothelial growth factor is expressed in the epiphyseal resting cartilage prior to the moment of canal formation and is continuously expressed until the establishment of a large secondary ossification centre. Interestingly, we found no expression of secretoneurin before the establishment of the canals although this factor attracts blood vessels under hypoxic conditions. Epiphyseal development further involves maturation of the resting chondrocytes into hypertrophic ones, associated with the mineralization of the cartilage matrix and eventual death of the latter cells. Our results suggest that vascular endothelial growth factor is the critical molecule for the generation of the epiphyseal vascular network in mice long bones. Secretoneurin, however, does not appear to be a player in this event. Hypertrophic chondrocytes undergo cell death by a mechanism interpreted as chondroptosis.

Prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods.

BACKGROUND: This study compared the efficacy of bacterial detection with inactivation for reducing the risk associated with transfusion of platelet (PLT) components contaminated with low levels of bacteria. STUDY DESIGN AND METHODS: Twenty-one double-dose PLTs were spiked with seven species of bacteria at three levels (0.003-0.03, 0.03-0.3, 0.3-3 colony-forming units [CFUs]/mL). After split, each PLT unit contained 1 to 10, 10 to 100, and 100 to 1000 CFUs. One unit was photochemically treated (PCT; 150 micromol/L amotosalen and 3 J/cm(2) ultraviolet A). The other unit was untreated. All units were stored and sampled on Days 1, 2, and 5 of storage for aerobic and anaerobic culture in the BacT/ALERT system (bioMérieux). PLTs were classified as sterile when no bacterial growth was detected after 120 hours of culture. RESULTS: In all PCT PLTs, no bacteria were detected throughout 5 days of storage regardless of species, level of contamination, and sampling time. In untreated PLTs, Staphylococcus aureus was consistently detected by culturing. Growth of 1 to 10 CFUs per unit Staphylococcus epidermidis, 1 to 100 CFUs per unit of Klebsiella pneumoniae, and 1 to 1000 CFUs per unit Propionibacterium acnes was delayed and only detectable after 5, 2, and 5 days of storage, respectively. Low levels of Streptococcus agalactiae (1-10 CFUs/unit), Escherichia coli (1-100 CFUs/unit), and Clostridium perfringens (1-100 CFUs/unit) were not detected during 5 days of storage, although bacterial outgrowth was detected at higher levels of contamination. CONCLUSIONS: For the seven bacterial species examined, contaminated PLTs may be released for transfusion on test-negative-to-date status. In contrast, bacterial inactivation by PCT could reduce the risk associated with transfusion of PLTs contaminated with low levels of these bacteria.