Background: Severe traumatic brain injury (TBI) has been increasing with greater incidence of injuries from traffic or sporting accidents. Although there are a number of animal models of TBI using progesterone for head injury, the effects of progesterone on neurologic outcome of acute TBI patients remain unclear. The aim of the present clinical study was to assess the longer-term efficacy of progesterone on the improvement in neurologic outcome of patients with acute severe TBI. Methods: A total of 159 patients who arrived within 8 hours of injury with a Glasgow Coma Score ≤ 8 were enrolled in the study. A prospective, randomized, placebo-controlled trial of progesterone was conducted in the Neurotrauma Center of our teaching hospital. The patients were randomized to receive either progesterone or placebo. The primary endpoint was the Glasgow Outcome Scale score 3 months after brain injury. Secondary efficacy endpoints included the modified Functional Independence Measure score and mortality. In a follow-up protocol at 6 months, the Glasgow Outcome Scale and the modified Functional Independence Measure scores were again determined. Results: Of the 159 patients randomized, 82 received progesterone and 77 received placebo. The demographic characteristics, the mechanism of injury, and the time of treatment were compared for the two groups. After 3 months and 6 months of treatment, the dichotomized Glasgow Outcome Scale score analysis exhibited more favorable outcomes among the patients who were given progesterone compared with the control individuals (P = 0.034 and P = 0.048, respectively). The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). The mean intracranial pressure values 72 hours and 7 days after injury were lower in the progesterone group than in the placebo group, but there was no statistical significance between the two groups (P > 0.05). Instances of complications and adverse events associated with the administration of progesterone were not found. Conclusion: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. Trial Registration: ACTRN12607000545460.

Hydroxyapatite (HAP) nanoparticles, typically 20 ± 5, 40 ± 10 and 80 ± 12 nm in diameter, were prepared and their effects on the proliferation of two bone-related cells, bone marrow mesenchymal stem cells (MSCs) and osteosarcoma cells (U2OS) were studied. The cell culture experiments showed improved cytophilicity of the nanophase mineral as compared with conventional HAP. Greater cell viability and proliferation of MSCs were measured on the nano HAP, remarkably for 20 nm sized particles. Interestingly, the growth of osteosarcoma cells was inhibited by the nano HAP and 20 nm sized particles were the best retardant. It is suggested that the HAP nanoparticles can exhibit favorable cell proliferation to optimize biological functionality, in which the particle size is believed to play a key role. These in vitro findings are of great significance for the understanding of cytophilicity and biological activity of nanoparticles during biomineralization.