Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: the BATMAN trial

Abstract:
Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures.

In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D.

Results:
All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm.

At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate.

There was a significant drop in lumbar spine (−5.4%) and hip (−4.5%) mean BMD, in the normal BMD group, none of whom received alendronate.

Fracture data will be presented.

Conclusion:
In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Dielectric percolative composites with high dielectric constant and low dielectric loss based on sulfonated poly(aryl ether ketone) and a-MWCNTs coated with polyaniline

Acidified multi-walled carbon nanotubes (a-MWCNTs) coated with polyaniline (PANI) (a-MWCNTs@PANI) nanofiller were prepared by in situ polymerization. Novel dielectric percolative composites, sulfonated poly(aryl ether ketone) (SPAEK)/a-MWCNTs@PANI, with high dielectric constant and low dielectric loss were fabricated using simple solution blending technique. A SPAEK/a-MWCNTs@PANI composite prepared in this fashion exhibited a high dielectric constant above 800, a dielectric loss tangent less than 1.1 at 10 kHz and room temperature. The morphological study of composites by SEM suggested that the in situ polymerization method of preparing a-MWCNTs@PANI nanofillers was useful to achieve good dispersion of fillers in SPAEK matrix.

One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing β-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and β-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced β-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates β-cell secretion without increasing amyloid formation and protects against amyloid-induced β-cell loss. This suggests a novel effect of sitagliptin to protect the β-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas.

An attack-resistant hybrid data-privatization method with low information loss

We examine a recent proposal for data-privatization by testing it against well-known attacks, we show that all of these attacks successfully retrieve a relatively large (and unacceptable) portion of the original data. We then indicate how the data-privatization method examined can be modified to assist it to withstand these attacks and compare the performance of the two approaches. We also show that the new method has better privacy and lower information loss than the former method.