Control of self-assembled morphology and molecular packing of asymmetric glycolipids by association/dissociation with poly(thiopheneboronic acid).

The molecular packing and self-assembled morphologies of asymmetric bolaamphiphiles, N-(2-aminoethyl)-N'-(ß-d-glucopyranosyl)alkanediamide [1(n), n = 12, 14, 16, 17, 18, and 20], were precisely controlled by association/dissociation with poly(thiopheneboronic acid) (PTB). Differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy revealed that the starting film of 1(n) associated with 1 equiv of the boronic acid moiety of PTB, (Film-1(n)PTB), had antiparallel molecular packing of 1(n) moiety within the monolayer membranes. However, the molecular packing of the starting film that contained 0.5 equiv of the boronic acid moiety of PTB (Film-2eq1(n)PTB) was parallel. The dispersion of Film-1(n)PTB in water gave only nanotapes, whereas that of Film-2eq1(n)PTB in water selectively formed nanotubes, through a dissociation reaction of PTB based on the hydrolysis of the boronate esters in the complexes. The nanotapes and nanotubes memorized the antiparallel and parallel molecular packing of the starting films, respectively. Changes in the length of the oligomethylene spacer of 1(n) never affected the molecular packing or self-assembled morphologies. However, the inner diameters of the nanotubes increased irregularly in the range of 67.9-79.6 nm as the length of the oligomethylene spacer of 1(n) increased from n = 12 to n = 18.

Improvement of the agitation granulation method to prepare granules containing a high content of a very hygroscopic drug.

This study describes a new approach to the preparation of a granulate with a high content of a very hygroscopic powder or drug, using the agitation granulation method, and the development of a tablet formulation using these granulates. A Chinese medicine extract, Hatimi-zio-gan, was used as the model of a very hygroscopic drug. Among the several excipients tested, only porous calcium silicate could be used to prepare granules, with a mixing ratio (extract to porous calcium silicate) from 2:1 to 20:1. With other excipients, very large lumps were formed during the granulation process. The best mixing ratio of extract to porous calcium silicate was 6:1. For preparation of the granules, water could be added to the mixed powder within a range of 1- to 4-times the amount of porous calcium silicate. From these results, it was concluded that the ability of porous calcium silicate to hold large amounts of water in its numerous pores may allow for the preparation of granulates with a high content of very hygroscopic drugs. Starch with partial alpha-links, carboxymethyl starch sodium salt and crospovidone were used for selection of the disintegration agent. When crospovidone was used as a disintegration agent, tablets containing about 70% of the Chinese medicine extract disintegrated in less than 7 min, with good dissolution rates. The same process was applied to extracts of Hotyu-ekki-to, Syo-seiryu-to, Boi-ogi-to and Bohu-tusyo-san. The absorption of paeoniflorin, a characteristic monoterpene glucoside contained in Hatimi-zio-gan extract, was evaluated in beagle dogs after oral administration of the Hatimi-zio-gan tablets prepared in this study. The values of C(max) and AUC obtained after administration of the tablets prepared in this study were significantly greater than those obtained for commercial tablets.

TSH receptor antibody measurements and prediction of remission in Graves' disease patients treated with minimum maintenance doses of antithyroid drugs.

Prediction of remission is one of the main problems of antithyroid drug (ATD) therapy for Graves' disease especially in patients who are treated with a minimum maintenance dose of ATD. We evaluated the ability of new sensitive TSH receptor antibody (TRAb) assays to predict remission in Graves' patients using two commercially available kits (TRAb-CT from Cosmic Corporation and TRAb-Dyno from Yamasa Corporation), compared to the original PEG assay. When a euthyroid state was achieved for more than 6 months with methimazole 5 mg/day or propylthiouracil 50 mg/day and thereafter for three months with 5 mg every other day or 50 mg every other day, respectively, we discontinued ATD medication. One year of observation after discontinuation of ATD was completed in 71 patients (60 females, median age 43 years, range 18-71), and TRAb values from these patients were analyzed in relation to prognosis. Twenty-six (37%) of the 71 patients had relapse of thyrotoxicosis and 45 remained euthyroid. The median TRAb levels in the relapse group were significantly higher than those in the remission group (P < 0.05). Relapse occurred in 15/51 patients negative by TRAb-CT, in 11/20 patients positive by TRAb-CT (chi2 = 4.1; P < 0.05), in 11/42 patients negative by TRAb-Dyno and in 15/29 patients positive by TRAb-Dyno (chi2 = 4.8; P < 0.05). By contrast, relapse occurred in 23/64 patients with negative TRAb by PEG assay and in 3/7 patients with PEG assay positive values (n.s.). All patients with TRAb-CT values of 30% inhibition or greater, or TRAb-Dyno values of 3.0 U/L or greater relapsed during the observation period. Thus, measurement of TRAb by the new sensitive assays is useful for prediction of remission in our patients.

Clinical evaluation of 3rd generation assay for thyrotropin receptor antibodies: the M22-biotin-based ELISA initiated by Smith.

Recently a new procedure for measuring serum TSH receptor (TSHR) autoantibody (TRAb) was reported by Smith et al. in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 (labeled with biotin) to TSHR-coated ELISA plate wells (pTRAb(3rd) assay). The aim of this study was to compare the performance of pTRAb(3rd) assay with pTRAb(2nd) assay based on inhibition of TSH-biotin binding to TSHR-coated ELISA plate wells. In addition, we evaluated the applicability of TRAb3rd assay to discriminate between untreated Graves' disease (GD) and painless thyroiditis (PT). Analysis of sera from 230 healthy controls indicated that only 1 (0.43%) gave inhibition of M22-binding values of greater than 15% (32.8% inhibition). To define the clinical cut-off point for a positive serum with autoantibodies to the TSHR, we performed receiver operating characteristic curve of the data from 244 untreated GD and three different control groups for pTRAb(3rd) assay. With a sensitivity of 99.6% at a cut-off of 14.5%, 22.0% and 22.0% inhibition of M22 binding, the specificity of healthy controls without PT, with PT and with PT excluding postpartum PT and PT during remission of GD was 99.6%, 96.6% and 97.5%, respectively. The pTRAb(3rd) assay was closely correlated to pTRAb(2nd) assay in the 244 untreated Graves' sera (r = 0.911). The pTRAb(3rd) assay detected 243 of 244 (99.6%) untreated GD, whereas 9.2% of PT and 6.7% of the subacute thyroiditis (SAT) were detectable. In contrast, pTRAb (2nd) assay detected 242 of 244 (99.2%) Graves' same sera, while 16.8 % from PT's same sera and 13.3% from SAT were detectable. In conclusion, pTRAb(3rd) assay has significantly (p = 0.0026) superior diagnostic accuracy for GD and PT, compared to that of pTRAb(2nd) assay.

EPMA observation between dentin and resin interfaces. Part 1. Comparison of wet and dry technique after short-term stored in water.

The study was to evaluate the marginal leakage of wet or dry dentin condition after restoration on short-term. In the study we used Photobond adhesive system and Single Bond adhesive system. The specimens were prepared from premolars. A class V cavity was prepared at the CEJ with a high-speed hand piece and #010 round diamond point. The cavity's walls and floors were etched with phosphoric acids of the test materials by wet and dry bonding techniques. The specimens were cross-sectioned longitudinally through the center of the cavities with a low speed diamond micro-cutter and polished with carbide paper (#600-1200) after storage in distilled water for 1 day, and silver nitrate staining. Specimens were viewed with EPMA for elemental distribution of calcium, nitrogen and silver on the resin-dentin interface. The uptake of silver particles was less in samples treated with the wet-bonding technique when compared with dry-bonding technique. This in vitro study showed that bonding technique is important in establishing a seal along the restoration margins to control marginal leakage.