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In most cells in which it exerts a variety of effects on cell proliferation, cell differentiation, and embryogenesis. It has also been shown to stimulate the production of extracellular matrix components including collagens and fibronectin and to play a pivotal role in fibrogenesis 12 ; . Thus, TGF- is considered to be a mediator of collagen production in the models of fibrogenesis. Significant progress has recently been made in our understanding of the expression of the collagen genes and their transcriptional regulation by TGF- 8, 9 ; . A recent report has shown that high glucose transiently induces a transcriptional activity of c-fos responsible for stimulation of the TGF 13 ; . However, there is little information regarding the interaction between AGE and c-Fos. We investigated here the expression of c-Fos in cultured mesangial cells treated with AGE and examined whether c-Fos affected the expression of TGF- . Furthermore, our recent report demonstrates that type IV collagen is up-regulated by AGE and its overexpression is transcriptionally regulated by Smad1 14 ; . Smad1 also enhances the levels of expression of type I collagen and osteopontin and plays a critical role in TGF mediated overexpression of extracellular matrix in diabetic nephropathy 14 ; . Therefore, we examined the role of Smad1 for regulating HSP47 expression by AGE stimulation in mesangial cells. In this study, we reported on a study of the inhibitory effect of OPB-9195 OPB ; , a novel inhibitor of AGEs formation, in a model of diabetic nephropathy. The pathogenic role of HSP47 in the development of the glomerulosclerotic lesions in diabetes was examined. We also confirmed the mechanism of these processes with the use of cultured mesangial cells. Protez Pharmaceuticals discovers, develops and commercializes innovative small molecule antibacterials for difficult-to-treat infections in the hospital. The company will leverage its validated antibacterial potentiator and anti-biofilm technology platforms and an IND stage antibiotic, to create a high value portfolio for the hospital antibacterial market. Protez also plans to strategically out-license or partner compounds from its programs that have applications in the community market.

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Of the comorbidity diabetes ; . It is unlikely that nonpharmaceutical interventions such as dietary counseling, staff encouragement, and follow-up visit variations were controlled in all 147 centers. Whether the centers were all primary care facilities or included subspecialty care could have impacted these other interventions because of variations in treatment regimens and goals for patients with diabetes and lipid abnormalities. Having few patients per center might also dilute patient anonymity, leading to unintended effects on compliance and other factors. Including a large number of sites can also lead to difficulty in controlling the introduction of investigator biases. For example, prerandomization bias may have occurred because it is unclear how patients were selected at each center. The authors state that they were "randomized.after washout and placebo run-in periods, " but how they were initially selected or if there were any selection criteria is unclear. Without a study-wide protocol to prevent enrollment bias toward failures of current lipid-lowering treatment, there could be a positive trend toward one study arm. Knowing the number of patients whose hypercholesterolemia was controlled or not controlled with what specific medications at selection is important if this study portends to evaluate first-line treatment options, as stated in the conclusion. Thus, it is possible that, by designing a study with such a large number of centers and resultant small number of patients per center, the efforts for randomness, double blinding, and clinical usefulness may have been defeated. David E. McMahon, MD Mount Carmel Medical Center Columbus, Ohio.

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