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Nonconverting CHR cases represented a heterogeneous group. Given that nonconverted subjects who remitted symptomatically also presented initially with less severe prodromal symptomatology and showed a distinct normative trajectory of both symptoms and psychosocial functioning over time, it may be possible to refine the CHR criteria to reduce the number of "false positive" cases by eliminating those who present with less severe attenuated positive symptoms or show early improvements in terms of symptoms or functioning.

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Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. In this study, we have shown that pharmacologic concentration (1mm) of melatonin significantly reduced cell migration and invasion of T98G and U251 glioma cells after 24-hr treatment and inhibited expression of matrix metalloproteinase 2 (MMP 2) and MMP 9. The melatonin inhibition of cell migration and invasion was associated with its reduction of intracellular basal free radical generation. Melatonin at pharmacologic concentration also inhibited the constitutive activation of the reactive oxygen species downstream transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, pyrrolidine dithiocarbamate, a NF-κB-specific inhibitor, at 10μm displayed anti-migration and invasion effects and inhibition of MMP 2 and MMP 9 expression resembling that of melatonin. Taken together, it is concluded that inhibition of migration and invasion of glioma cells by melatonin is associated with the latter in its inhibition of oxidative stress pathway. This suggests a potential therapeutic application of melatonin in the treatment of glioma.

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The thrombin-related peptide, TP508, has been shown to promote soft tissue healing and fracture repair. One possible clinical application of TP508 is to accelerate bone regeneration during distraction osteogenesis, which is a lengthy procedure involving significant complications. In this study, we tested the ability of TP508 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Twenty-three rabbits had left tibiae lengthened for 1 cm over a period of 6 days. T P 508 (0, 30 and 300 pg in 300 pI saline) was injected into the distraction gaps at the beginning and the end of the lengthening phase, and all the animals were killed 2 weeks after lengthening. By the end of experiment, more animals in the TP508 treated groups had complete bony union of the distraction gaps when compared to the saline treated group. pQCT examination of the regenerates demonstrated a significantly greater bone mineral density (BMD) in the TP508 treated groups relative to the saline control group, but no statistical difference in the BMD was found between the two dosages of TP508. Bone consolidation and bone remodeling was far advanced in the TP508 300 pg treated group, and the regenerates mainly consisted of well-vascularized woven bone. In contrast, in the group that received the 30 pg TP508 treatment, focal bone defects and discontinuities of the new cortices were evident in some but not all animals. In the saline control group a majority of the animals showed large amounts of fibrous and cartilaginous tissues in the regenerates, and none of the regenerates had completed consolidation. This study has demonstrated that local application of TP508 enhanced bone formation and consolidation during distraction osteogenesis in the rabbit. The findings indicate that TP508 may be useful in promoting osteogenesis in situations when augmentative treatment for bone formation and consolidation are needed.

Sulfatides, normal components of serum lipoproteins, may play an important role in cardiovascular disease due to their various modulatory functions in haemostasis. The incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis has been reported to be approximately 10 to 30 times higher than that in the general population. To elucidate the possible roles of serum sulfatides in this high incidence, we measured the level of sulfatides in 59 such patients, by converting them to lysosulfatides according to a recently developed quantitative, qualitative, high-throughput technique using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The mean level of sulfatides in patients 3.58 +/- 1.18 nmol/ml was significantly lower than that in age-matched normal subjects (8.21 +/- 1.50 nmol/ml; P < 0.001). Patients receiving maintenance hemodialysis over a longer period had lower levels of sulfatides. When the mean levels of sulfatides were compared between patients with cardiovascular disease (N = 22) and those without the disease (N = 37), the level in the former group 2.85 +/- 0.67 nmol/ml was found to be significantly lower than that in the latter group 4.01 +/- 1.22 nmol/ml (P < 0.001). These findings reveal a close correlation between low levels of serum sulfatides and a high risk of cardiovascular disease in these patients. Determination of the level of serum sulfatides can contribute to predictions of the incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis.