Release Property of Progesterone from a Mixed-Base Suppository Consisting of Witepsol® W35 and Witepsol® E85

The mechanism of drug release from progesterone suppositories that consist of two types of hard fat (Witepsol® W35 and Witepsol® E85) was investigated. The strength, the thermodynamic characteristics, the surface structures, the drug release property, methylene blue penetration into suppositories, and change of surface structure after the dissolution test were employed for detecting characteristics of progesterone suppositories. The formulation with a mixing ratio of Witepsol W35 and Witepsol E85 at a 1:1 ratio showed the maximum strength value. The peak temperature of the suppositories showed a tendency to increase with increases in the ratio of Witepsol E85. The maximum height of the profiles measured with laser microscopy, from 20.8 μm to 29.2 μm, reached a maximum after 3 h of the dissolution test. When the suppositories were immersed in pH 7.4 phosphate buffer containing 0.5% methylene blue at 37°C, the penetrating area increased with time. The weight of the suppositories also increased with time. According to these findings, it was suggested that the release of drug from a mixed type of suppository containing progesterone was via the matrix and pores.     

Effect of reaction temperature on Fe–Al analcime formation

The effects of reaction period, temperature, and iron species on the zeolite framework type were studied in this work. Gismondine (GIS) is usually synthesized by hydrothermal method at 80°C from sodium metasilicate and aluminum nitrate as starting materials preferentially independent of the presence/absence of iron source. However, the present work revealed that pure analcime (ANA) could be formed at temperatures more than 120°C. A large polyhedral ANA crystal with a diameter of 180 μm was obtained even at a comparatively low temperature such as 150°C at a short reaction period of 1 week. The presence of iron source promoted the formation of pure ANA. Infrared spectroscopy, X-ray diffraction, and ICP-OES analysis suggested that the iron component added as a reactant was incorporated into the ANA framework through the isomorphous substitution for Al.     

Statistical failure analysis of adhesive resin cement bonded dental ceramics

The goal of this work is to quantitatively examine the effect of adhesive resin cement on the probability of crack initiation from the internal surface of ceramic dental restorations. The possible crack bridging mechanism and residual stress effect of the resin cement on the ceramic surface are examined. Based on the fracture-mechanics-based failure probability model, we predict the failure probability of glass-ceramic disks bonded to simulated dentin subjected to indentation loads. The theoretical predictions match experimental data suggesting that both resin bridging and shrinkage plays an important role and need to be considered for accurate prognostics to occur.     

Pharmaceutical quantification with univariate analysis using transmission Raman spectroscopy

The purpose of this study was to investigate the quantification performance of transmission Raman spectroscopy with univariate analysis. Model dosage forms containing acetaminophen and an excipient, lactose monohydrate, were prepared. The Raman spectra of the tablets were obtained using the modes of transmission, backscattering micro-spectroscopy, and wide area illumination. Calibration curves for quantification of acetaminophen in the tablets were created using peak heights of the Raman spectra. Of the three modes of measurement, the quantitative results by transmission had the highest correlation with those by conventional UV–vis methods. In the validation of quantification by the transmission mode with univariate analysis, a certain degree of daily variation was confirmed. Additionally, quantitative results using peak heights were compared with those of partial least squares (PLSs) multivariate analysis. The root mean square error of prediction (RMSEP) suggested that quantification using PLS provided better precision than the peak height method as expected. However, content uniformity test using large sample sizes by the Raman spectra is not required to be very highly predictive because they usually employ non-parametric criteria and include wide specification ranges. Therefore, univariate analysis using transmission Raman spectroscopy was a suitable quantitative method for conducting content uniformity tests of large sample sizes.     

Human tracking with variable prediction steps based on Kullback-Leibler divergence

This article deals with a path-planning problem in tracking humans in order to obtain detailed information about human behavior and characteristics. In our method, path planning is performed based on Kullback-Leibler (KL) divergence between the predicted distribution of all human positions and the intensity of the field of view of the agents. The number of steps predicted is determined according to the consistency of the prediction. Experimental results show that when the prediction of human movement is accurate, long-term prediction is useful for path planning. On the other hand, when prediction is inaccurate, long-term prediction might not be useful. Our path-planning method works well even under changing circumstances by changing the length of the predictions.     

Chemistry,Properties, and in Vitro and in Vivo Applications of 2′‐O‐Methoxyethyl‐4′‐thioRNA,a Novel Hybrid Type of Chemically Modified RNA

We report the synthesis, properties, and in vitro and in vivo applications of 2′‐O‐methoxyethyl‐4′‐thioRNA (MOE‐SRNA), a novel type of hybrid chemically modified RNA. In its hybridization with complementary RNA, MOE‐SRNA showed a moderate improvement of T_m value (+3.4 °C relative to an RNA:RNA duplex). However, the results of a comprehensive comparison of the nuclease stability of MOE‐SRNA relative to 2′‐O‐methoxyethylRNA (MOERNA), 2′‐O‐methyl‐4′‐thioRNA (Me‐SRNA), 2′‐O‐methylRNA (MeRNA), 4′‐thioRNA (SRNA), and natural RNA revealed that MOE‐SRNA had the highest stability (t_1/2>48 h in human plasma). Because of the favorable properties of MOE‐SRNA, we evaluated its in vitro and in vivo potencies as an anti‐microRNA oligonucleotide against miR‐21. Although the in vitro potency of MOE‐SRNA was moderate, its in vivo potency was significant for the suppression of tumor growth (similar to that of MOERNA).     

2,3-Dihydrohomofarnesal: Female Sex Attractant Pheromone Component of Callosobruchus rhodesianus (Pic)

Callosobruchus rhodesianus (Pic) (Coleoptera: Chrysomelidae: Bruchinae) is a pest of stored legumes through the Afro-tropical region. In laboratory bioassays, males of C. rhodesianus were attracted to volatiles collected from virgin females. Collections were purified by various chromatographic techniques, and the biologically active component isolated using gas chromatographic-electroantennographic detection analysis. Gas chromatography-mass spectrometry and NMR analyses suggested that the active compound was 2,3-dihydrohomofarnesal, i.e., 7-ethyl-3,11-dimethyl-6,10-dodecadienal. The structure was confirmed by non-stereoselective and enantioselective total synthesis. Using chiral gas chromatography, the absolute configuration of the natural compound was confirmed as (3S,6E)-7-ethyl-3,11-dimethyl-6,10-dodecadienal. Y-tube olfactomter assays showed that only the (S)-enantiomer attracted males of C. rhodesianus. The (R)-enantiomer and racemate did not attract males, suggesting that the (R)-enantiomer inhibits the activity of the natural compound. In combination with previous reports about sex attractant pheromones of congeners, we suggest that a saltational shift of the pheromone structure arose within the genus Callosobruchus.     

Effects of Wnt-10b on proliferation and differentiation of adult murine skin-derived CD34 and CD49f double-positive cells

Although mouse Wnt-10b has been shown to play various roles in a wide range of biological actions, the effects on epithelial stem/progenitor cells in the skin have not been reported. In the present study, we investigated the effects of Wnt-10b on proliferation and differentiation of murine skin-derived CD34 and CD49f double-positive (CD34⁺CD49f⁺) cells, a supposed fraction as enriched epithelial stem/progenitor cells. The cells were prepared from dorsal skin samples obtained from young adult mice as α6 integrin (CD49f) and CD34 double-positive cells by fluorescent activated cell sorting (FACS), and they were cultured with or without Wnt-10b to investigate its effects on proliferation and differentiation. Involvement of canonical Wnt signaling pathway was confirmed by TOPFLASH assay, and differentiation of the CD34⁺CD49f⁺ cells was assessed by RT-PCR analysis and immunocytochemical examinations. The skin-derived CD34⁺CD49f⁺ cells were immunopositive for Lhx2 and expressed mRNA of classical markers for bulge stem cells, including Lhx2, keratin15, Sox9, S100a6, and NFATc1. Their proliferation was suppressed by Wnt-10b, and the markers for differentiated epithelial cells became to be expressed in the culture with Wnt-10b. These results suggest that Wnt-10b promotes differentiation of epithelial stem/progenitor cells in the skin.     

Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues

In obesity, adipocyte hypertrophy and chronic inflammation in adipose tissues cause insulin resistance and type‐2 diabetes. Trigonella foenum‐graecum (fenugreek) can ameliorate hyperglycemia and diabetes. However, the effects of fenugreek on adipocyte size and inflammation in adipose tissues have not been demonstrated. In this study, we determined the effects of fenugreek on adipocyte size and inflammation in adipose tissues in diabetic obese KK‐Ay mice, and identified the active substance in fenugreek. Treatment of KK‐Ay mice with a high fat diet supplemented with 2% fenugreek ameliorated diabetes. Moreover, fenugreek miniaturized the adipocytes and increased the mRNA expression levels of differentiation‐related genes in adipose tissues. Fenugreek also inhibited macrophage infiltration into adipose tissues and decreased the mRNA expression levels of inflammatory genes. In addition, we identified diosgenin, a major aglycone of saponins in fenugreek to promote adipocyte differentiation and to inhibit expressions of several molecular candidates associated with inflammation in 3T3‐L1 cells. These results suggest that fenugreek ameliorated diabetes by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues, and its effects are mediated by diosgenin. Fenugreek containing diosgenin may be useful for ameliorating the glucose metabolic disorder associated with obesity.     

Dietary Marine-Derived Tocopherol has a Higher Biological Availability in Mice Relative to Alpha-Tocopherol

The biologic availability of two kinds of tocomonoenols, marine-derived tocopherol (MDT) and α-tocomonoenol, was investigated in ICR mice. Vitamin E-deficient ICR mice were fed MDT and α-tocomonoenol together with α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol, and storage in liver, spleen, lung, and brain was quantified using reverse-phase high-performance liquid chromatography. The vitamin E relative biologic availability (VE-RBA) in liver was 100 for α-tocopherol, 26 ± 3 for β-tocopherol, 4 ± 2 for γ-tocopherol, not detected for δ-tocopherol, 49 ± 6 for MDT, and 30 ± 7 for α-tocomonoenol. The VE-RBA in brain was 100 for α-tocopherol, 5 ± 2 for β-tocopherol, not detected for γ-tocopherol and δ-tocopherol, 8 ± 1 for MDT, and 4 ± 1 for α-tocomonoenol. Tocopherols and tocomonoenols did not accumulate in the spleen or lung. MDT and α-tocomonoenol had high VE-RBA values. The VE-RBA value for MDT was much higher than that for β-tocopherol.