A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further evaluated in a clinical study of prostate-, lung- and breast-cancer patients stratified according to skeletal metastases. A technically robust ELISA assay specific for a MMP-2, -9 and -13 neo-epitope was produced and seen to be statistically elevated in BDL rats compared to baseline levels as well as significantly elevated in CCL4 rats stratified according to the amount of total collagen in the livers. CO1-764 levels also correlated significantly with total liver collagen and type I collagen mRNA expression in the livers. Finally, the CO1-764 marker was not correlated with skeletal involvement or number of bone metastases. This ELISA has the potential to assess the degree of liver fibrosis in a non-invasive manner.

Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discuss how osteopetrosis models have clarified the function of the coupling of bone formation to bone resorption, and the pivotal role of the osteoclast and their function in this phenomenon. We highlight the distinct possibility that osteoclast activities can be divided into two separate avenues: bone resorption and control of bone formation.

Endomorphins (EMs

The effect of melatonin on inhibition of cell growth was studied in CT‐26, a murine colon carcinoma‐derived cell line. Cells growing in exponential phase were exposed to low (10−7–10−10 M) and high doses (1, 2 and 3 × 10−3 M) of melatonin during 24 h. Synthesis of DNA was measured by 5‐bromo‐2′‐deoxyuridine incorporation. There was no effect at low doses, but a statistically significant correlation was found between the decrease in DNA synthesis and the dose of melatonin used (r = −0.52, P < 0.001). This implied the following percentages of inhibition: 1 mM, 22%; 2 mM, 25%; 3 mM, 47%. Potential cell membrane damage by high doses of melatonin was investigated by lactate dehydrogenase measurement and no significant levels were observed. Analysis with a single saturation technique showed no detectable oestradiol receptors in this cell type; therefore, we can assume that the effects occurring with the addition of melatonin were not mediated by modulation of this hormone on oestrogen receptors. The decreases in cell growth were attributed to a moderate, but significant antiproliferative action of melatonin on this non‐hormone‐dependent cell line. Copyright © 2000 John Wiley & Sons, Ltd.

The data suggest that MMP-9-mediated CO3 turnover is a central event in the pathogenesis of fibrosis, and that the neo-epitope generated may be a novel biochemical marker.