To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.

This study was performed to determine if recombinant human osteogenic protein-] (rhOP-I) is effective in promoting matrix synthesis and matrix formation by rabbit nucleus pulposus (NP) and annulus fibrosus (AF) cells cultured in alginate beads. The effects of culturing the cells in the presence of various concentrations of rhOP-1 were assessed by measuring changes in cell proliferation, proteoglycan (PG) and collagen synthesis and mRNA expression, and in the matrix contents of PG and collagen, as indicators of matrix accumulation. At high concentrations, rhOP-l had a moderate mitogenic effect on both NP and A F cells. It also stimulated the synthesis of PG and collagen in a dose-dependent manner: this was associated with a corresponding increase in the expression of mRNA for aggrecan core protein and collagen type 11. The stimulatory effect of rhOP-1 on PG synthesis was more pronounced than that on collagen synthesis. Continuous treatment with rhOP-1 led to an increase in the total DNA, P G and collagen contents in both N P and A F cultures. The results presented here provide evidence of the ability of rhOP-l to stimulate the metabolism of both rabbit A F and N P cells cultured in alginate beads.

In order to find out whether high intensity focused ultrasound (HIFU) might be useful against hepatocellular carcinoma, we analyzed the effect of a microbubble agent (Levovist) on the temperature rise and tissue necrosis induced by HIFU. Rabbits were given 7 ml Levovist (300 mg/ml) or saline intravenously. Up to six areas per rabbit liver were exposed to HIFU for 60 s (2.18 MHz, I(SPTA)=400 W/cm(2)). The volume of the tissue coagulated by HIFU was measured 10 min after the start of HIFU. HIFU-induced lesions were larger in the animals given Levovist: (mm(3), Levovist versus saline) 371+/-104 versus 166+/-71 (P<0.001). Temperatures in the animals given Levovist were also higher 60 s after the start of exposure: ( degrees C, Levovist versus saline) 20.3+/-3.5 versus 13.2+/-3.8 (P<0.001). The amount of damage differed greatly, but the pathological changes caused by HIFU with Levovist were the same as those caused by HIFU with saline. Hemorrhagic areas and implosion cysts were seen, and many cells had been disrupted or destroyed. Microbubble agents developed for diagnostic uses could also be used in anticancer therapy.

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