Collagenase and tissue plasminogen activator production in developing rat calvariae: normal progression despite fetal exposure to microgravity.

Exposure to zero gravity has been shown to cause a decrease in bone formation. This implicates osteoblasts as the gravity-sensing cell in bone. Osteoblasts also are known to produce neutral proteinases, including collagenase and tissue plasminogen activator (tPA), which are thought to be important in bone development and remodeling. The present study investigated the effects of zero gravity on development of calvariae and their expression of collagenase and tPA. After in utero exposure to zero gravity for 9 days on the NASA STS-70 space shuttle mission, the calvariae of rat pups were examined by immunohistochemistry for the presence and location of these two proteinases. The ages of the pups were from gestational day 20 (G20) to postnatal (PN) day 35. Both collagenase and tPA were found to be present at all ages examined, with the greatest amount of both proteinases present in the PN14 rats. At later ages, high amounts were maintained for tPA but collagenase decreased substantially between ages PN21 to PN35. The location of collagenase was found to be associated with bone-lining cells, osteoblasts, osteocytes, and in the matrix along cement lines. In contrast, tPA was associated with endothelial cells lining the blood vessels entering bone. The presence and developmental expression of these two proteinases appeared to be unaffected by the exposure to zero gravity. The calvarial thickness of the pups was also examined; again the exposure to zero gravity showed little to no effect on the growth of the calvariae. Notably, from G20 to PN14, calvarial thickness increased dramatically, reaching a plateau after this age. It was apparent that elevated collagenase expression correlated with rapid bone growth in the period from G20 to PN14. To conclude, collagenase and tPA are present during the development of rat calvariae. Despite being produced by the same cell in vitro, i.e., the osteoblast, they are located in distinctly different places in bone in vivo. Their presence, developmental expression, and quantity do not seem to be affected by a brief exposure to zero gravity in utero.

Scarring alopecia in neonates as a consequence of hypoxaemia-hypoperfusion.

Scarring alopecia is relatively uncommon in infants and children and rarely discussed in the paediatric literature. It does not appear to have been previously documented as a consequence of compromised oxygenation and blood supply in the neonatal population or as a complication of extracorporeal membrane oxygenation (ECMO) treatment. During a six month period, we observed five patients who presented to our neonatal intensive care unit with pressure ulcers that eventuated in scarring alopecia. The patients were all > or = 2500 g at birth, had some disruption of the cardiac circulation, were hypoxaemic and acidotic, and required vasopressor treatment. Institution of a positioning schedule and use of a thermostable Spenco gel pad during the subsequent six month period eliminated the presence of pressure ulceration and scarring alopecia in this at-risk population. Although scarring alopecia is a permanent condition, skin changes preceding its development in this setting are recognisable and follow a predictable pattern and time course, and should therefore allow for intervention at an earlier stage. Neonatal ECMO patients, as well as those who suffer hypoxaemia-hypoperfusion, but do not require circulatory bypass, appear to be at increased risk for development of the pressure ulcers that precede scarring alopecia. Paediatricians should consider this possibility and seek the appropriate historical information when confronted with a case of scarring alopecia after the neonatal period.