Open-label, multicenter, dose-titration study to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone.

The purpose of this study was to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This multicenter, open-label, dose-escalation, phase III study enrolled Japanese patients (20-85 years old) with hyponatremia secondary to SIADH who were unresponsive to fluid restriction. Oral tolvaptan was administered for up to 30 days, initially at 7.5 mg/day, but escalated daily as necessary, based on the serum sodium concentration and safety, over the first 10 days until the optimal maintenance dose was determined for each patient (maximum 60 mg/day). The primary endpoint was the proportion of patients with normalized serum sodium concentration on the day after the final tolvaptan dose. Secondary endpoints included the mean change in serum sodium concentration from baseline on the day after the final dose. Sixteen patients (male, 81.3%; mean ± standard deviation age 71.9 ± 6.1 years) received tolvaptan treatment and 11 patients completed the study with one patient re-administered tolvaptan in the treatment period. Serum sodium concentrations normalized in 13 of 16 (81.3%) patients on the day after the final tolvaptan dose. The mean change in serum sodium concentration from baseline on the day after the final dose was 11.0 ± 4.3 mEq/L. Adverse events considered related to tolvaptan (10 [62.5%] patients) were generally of mild to moderate severity. Oral tolvaptan corrects hyponatremia in Japanese patients with SIADH with a similar efficacy and safety profile as that noted in non-Japanese patients.

Virus-templated photoimprint on the surface of an azobenzene-containing polymer.

A photoimprint-based immobilization process is presented for cylindrical viruses on the surface of an azobenzene-bearing acrylate polymer by using atomic force microscopy (AFM). Tobacco mosaic virus (TMV), 18 nm in diameter and ca. 300 nm in length, was employed as a model virus. First, a droplet of an aqueous solution containing TMV was placed on the acrylate polymer surface. After drying the droplet, the polymer surface was irradiated with light at a wavelength of 470 nm from blue-light-emitting diodes. Finally, the surface was washed by aqueous solution with detergents. The polymer surface was observed at each step by AFM. TMV was shown to embed itself gradually on the polymer surface during photoirradiation in a time scale of tens of minutes because of the formation of the surface groove complementary to the shape of TMV. Analysis of immobilization efficiency of TMV on the polymer surface by the immunological enzyme luminescence indicated that efficiency increased proportional to the photoirradiation time. In these experimental conditions, the absorption band of the azobenzene moiety remained constant before and after the photoirradiation. These results show that TMV is physically held on the complementary groove formed on the polymer surface by the photoirradiation.

Orientation control of photo-immobilized antibodies on the surface of azobenzene-containing polymers by the introduction of functional groups.

In our photo-induced immobilization technique for an antibody (IgG) using azopolymers, the introduction of COOH and NMe(2) into the azopolymers, which can introduce surface charges, strongly affected the immobilization properties such as the efficiency of immobilization and the activity of the immobilized IgG (i.e., the orientation of the immobilized IgG). The introduction of COOH promoted a more active orientation of the immobilized IgG. The orientation was determined during the adsorption process onto the azopolymer surface in solution before photo-immobilization, and was maintained during the photo-immobilization. The surface charge of the azopolymer appears to be an important factor for IgG orientation, which involves electrostatic interactions between its Fab and the azopolymer surface.