Harikai N.,Mukogawa Womens University
General Physiology and Biophysics | Year: 2012
To gain insight into the molecular mechanism of hyper-glucocorticoidism in spontaneously hypertensive rats (SHR), this study investigated the expression of genes related to glucocorticoid synthesis, melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage enzyme (P450scc) and 11β-hydroxylase (P450c11), and the transcription factors of steroidogenic factor 1 (SF-1), which stimulates expression of the above gene, and DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene 1), which negatively regulates the transcriptional activity of SF-1, in adrenals from SHR. On quantitative real time RT-PCR analysis, gene expression levels of MC2R, StAR, P450scc and P450c11 in SHR were high compared with those in normotensive Wistar Kyoto rats (WKY). The gene expression level of SF-1 was not different between the two rats. However, the expression level of DAX-1 in SHR was markedly lower than that in WKY. Furthermore, the protein levels of StAR, SF-1 and DAX-1 determined by Western blot analysis coincided well with the gene expressions in both rats. These results suggest that the low level of DAX-1 may enhance the transcriptional activity of SF-1 and expression of genes related to glucocorticoid synthesis, which are targeted by SF-1, in adrenals from SHR.
Uchida T.,Mukogawa Womens University
Yakugaku Zasshi | Year: 2015
In this symposium we focused on trade-offs which might occur in the process of development of many types of formulation and corresponding dissolution methods. Firstly, we focused on a solubility-permeability trade-off in the case of micelle with surfactant or molecular complex with CyD. The micelle would be successful in increasing drug solubility, however it rather decreased permeability of model drug progesterone (Biopharmaceutics Classfication System (BCS) Class II) as an overall flux. Secondly in order to reduce bitterness of branched chain amino acid (BCAA), increasing particle sizes of each amino acid crystals involved in formulation was effective since the release rate of amino acid was restricted effciently. Thirdly, in the case of injection of paclitaxel (BCS Class II)formulation, the drug was adsorbed to albumin. Thereby the risk of allergy was dramatically decreased compared to the case when non-ionic surfactant was used as an additive. Fourth, anticancer drug was incorporated into the internal (core) phase of an orally disintegrating tablet (ODT), this is also merit to avoid exposure of the drug to a nursing person or individual working person in manufacturing process. Fifth, the convenient syringe type kit pharmaceutical preparation for administration of total parenteral nutrition (TPN) to avoid incompatibility and its risk management effect was briefly discussed. Finally, the risk of an additive such as alcohol for a preterm infant was described. © 2015 The Pharmaceutical Society of Japan
Mera H.,Mukogawa Womens University
Clinical calcium | Year: 2013
Since the days of ancient Greece, it has been known that articular cartilage has poor potential to repair. In April, 2013, autologous chondrocyte implantation (ACI) was approved by the Japanese ministry of Health, Labour and Welfare, as the first orthopedic cell therapy in Japan. Half a century has passed since Chesterman's report on rabbit allogeneic chondrocyte implantation, and approximately 20 years since the first human ACI report by Brittberg. In Japan, 24 years has passed since Wakitani's allogeneic chondrocyte implantation, and over 10 years since the human ACI report by Ochi. A long-term follow-up clinical trial with the high statistical power is needed to verify the safety and efficacy of new cartilage joint therapy. Moreover, we need the infrastructure, including drug and/or device regulation and timely approved by the government, to apply new therapies in similar time frames to other developed nations.
Takatani-Nakase T.,Mukogawa Womens University
Yakugaku Zasshi | Year: 2013
The diabetes patients have been associated with an increased risk of mortality by breast cancer, and there are differences in the regimen choice and effects of breast cancer treatment between the breast cancer patients with diabetes and their nondiabetic counterparts. However, the pathophysiological relationships of diabetes and breast cancer have not yet been elucidated in detail, therefore its evaluation is strongly required to achieve novel treatment strategies for breast cancer with hyperglycemia. Extracellular circumstances of cancer cells can influence the growth and behavior, resulting in invasion, metastasis and tumor development. We demonstrated that breast cancer cells, MCF-7, cultured in hyperglycemic level significantly promotes the motile activity in comparison to normal physiological glucose level. Moreover, Zn2+ uptake activity into cellular cytosol and the mRNA expression of zinc transporters, ZIP6 and ZIP10, in the high glucose-exposed cells were shown to be especially higher than in the physiological glucose level. The depletion of intracellular Zn2+ by zinc chelation and ZIP6 or ZIP10 knockdown blocked the high migration activity, indicating that Zn2+ transported via ZIP6 and ZIP10 plays an essential role in the promotion of cell motility stimulated in high glucose level. These findings provide a proposing target of the novel strategies for the diagnosis and therapy of breast cancer with hyperglycemia. © 2013 The Pharmaceutical Society of Japan.
Yamagata K.,Nihon University |
Tagami M.,Chiyoda Corporation |
Yamori Y.,Mukogawa Womens University
Nutrition | Year: 2015
Vascular endothelial cell (EC) dysfunction strongly induces development of cardiovascular and cerebrovascular diseases. Epidemiologic studies demonstrated a preventative effect of dietary polyphenols toward cardiovascular disease. In studies using cultured vascular ECs, polyphenols were recognized to regulate nitric oxide and endothelin-1 (ET-1) production. Furthermore, epigallocatechin-3-gallate inhibited the expression of adhesion molecules by a signaling pathway that is similar to that of high-density lipoprotein and involves induction of Ca2+/calmodulin-dependent kinase II, liver kinase B, and phosphatidylinositol 3-kinase expression. The effects of polyphenols on ECs include antioxidant activity and enhancement of the expression of several protective proteins, including endothelial nitric oxide synthase and paraoxonase 1. However, the observed effects of dietary polyphenols invitro do not always translate to an invivo setting. As such, there are many questions concerning their physiological mode of action. In this review, we discuss research on the effect of dietary polyphenols on cardiovascular disease and their protective effect on EC dysfunction. © 2015 Elsevier Inc.