Drug-drug interactions

Several drugs are using to obtain a desired therapeutic objective or to treat coexisting diseases. The choice of drugs should be dependent on pharmacological characteristics. Interactions may be either pharmacokinetic or pharmacodynamic. In pharmacokinetic interaction, drugs may interact at any point during their absorption, distribution, metabolism, or excretion; the result may be an increase or decrease in the concentration of drug at the site of action. Metabolic enzyme, cytochrome P450, which metabolites any drugs is important in pharmacokinetic interaction. As characteristics change in their rates of disposition of using drug, the magnitude of an interaction that changes pharmacokinetic parameter is not always predictable but can be very significant. In pharmacodynamic interaction, drugs may interact at common receptor site or have additive or inhibitory effects due to actions at different sites in an organ. A drug interaction should be suspected danger when unexpected effects are observed. Careful drug histories are important, because patients may take over-the-counter drugs, may take drugs prescribed by another physician, or may take drugs prescribed for another patient. Care should be exercised when major changes are made in a drug regimen. Then, drugs that are not necessary should be discontinued. The major work of the medical staff of a hospital is to determine if an interaction has occurred and the magnitude of its effect. The interacting drugs should be used effectively with adjustment of dosage or other therapeutic modifications when an interaction is observed

Combinational Treatment of Trichostatin A and Vitamin C Improves the Efficiency of Cloning Mice by Somatic Cell Nuclear Transfer.

Somatic cell nuclear transfer (SCNT) provides a unique opportunity to directly produce a cloned animal from a donor cell, and it requires the use of skillful techniques. Additionally, the efficiencies of cloning have remained low since the successful production of cloned animals, especially mice. There have been many attempts to improve the cloning efficiency, and trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to enhance the efficiency of cloning. Here, we report a dramatically improved cloning method in mice. This somatic cell nuclear transfer method involves usage of Hemagglutinating virus of Japan Envelope (HVJ-E), which enables easy manipulation. Moreover, the treatment using two small molecules, TSA and vitamin C (VC), with deionized bovine serum albumin (dBSA), is highly effective for embryonic development. This approach requires neither additional injection nor genetic manipulation, and thus presents a simple, suitable method for practical use. This method could become a technically feasible approach for researchers to produce genetically modified animals from cultured cells. Furthermore, it might be a useful way for the rescue of endangered animals via cloning

Possible role of bradykinin on stimulus-secretion coupling in adrenal chromaffin cells

Nonapeptide bradykinin is known to be a central nervous system neurotrans-mitter and to play a role in regulation of neuronal function. However, few details are known of the function of its peptide on stimulus-secretion coupling in neuronal cells. In this article, the role of bradykinin on catecholamine biosynthesis, secretion and Ca2+movement in adrenal chromaffin cells as a model for catecholamine-containing neurons are examined. Bradykinin receptors are classified as B1 and B2 receptor subtypes. These receptors are present on the adrenal chromaffin cell membrane. Bradykinin increases the influx of Ca2+ and the turnover of phosphoinositide through the stimulation of bradykinin B2 receptor. The secretion of catecholamine from the cells is initiated by the raise of [Ca2+]i. An increase in [Ca2+]i and production of diacylglycerol stimulate the activation of calcium-dependent protein kinases. These kinases stimulate the activation of tyrosine hydroxylase, a rate-limiting enzyme in the biosynthesis of catecholamine. Otherwise, bradykinin increases Ca2+ efflux from the cells through the stimulation of the bradykinin-B2 receptor. This action may be explained by an extracellular Na+-dependent mechanism, probably through acceleration of Na+/Ca2+ exchange. It is interesting that bradykinin, which stimulates the biosynthesis and secretion of catecholamine in adrenal chromaffin cells, plays a role in the termination of calcium-signal transduction through the stimu-lation of Ca2+ efflux from the cells

Cyclical and Patch-Like GDNF Distribution along the Basal Surface of Sertoli Cells in Mouse and Hamster Testes

BACKGROUND AND AIMS: In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs) through GDNF family receptor α1 (GFRα1). It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules

トクシマ ダイガク ヤクガクブ ノ ヤクザイシ キョウイク ニオケル ジシュ サンカガタ イリョウ ヤクガク カモク ノウドウ ガクシュウ セイド ノ ドウニュウ ト ソノ セイカ

徳島大学薬学部では2007年度より学生自主参加型医療薬学科目（能動学習制度）を導入している。開始7年目となる本年，本制度における過去の研修会の開催状況と出席状況の分析を行うとともに，2013年6月，学生の意識調査をおこなった。意識調査の結果，学生の出席意欲は全体的に積極的とは言えないものであったが，学習を継続していく必要性に対する認識度は学年が上がるにしたがって高まっており，学生の意識変化が明らかとなった。医療の世界で活躍する人材を育成するためには，生涯にわたって学習する意識を育てることが不可欠である。今回の調査により，本制度の現状と有用性が明らかとなった

Genome-Wide Association Study Adjusted for Occupational and Environmental Factors for Bladder Cancer Susceptibility

This study examined the effects of single-nucleotide polymorphisms (SNPs) on the development of bladder cancer, adding longest-held occupational and industrial history as regulators. The genome purified from blood was genotyped, followed by SNP imputation. In the genome-wide association study (GWAS), several patterns of industrial/occupational classifications were added to logistic regression models. The association test between bladder cancer development and the calculated genetic score for each gene region was evaluated (gene-wise analysis). In the GWAS and gene-wise analysis, the gliomedin gene satisfied both suggestive association levels of 10−5 in the GWAS and 10−4 in the gene-wise analysis for male bladder cancer. The expression of the gliomedin protein in the nucleus of bladder cancer cells decreased in cancers with a tendency to infiltrate and those with strong cell atypia. It is hypothesized that gliomedin is involved in the development of bladder cancer

Mineralization induced by phosphorylated dry baker's yeast.

We found the mineralization of Cu during long-term Cu2+ adsorption onto dry baker's yeast cells phosphorylated using sodium cyclo-triphosphate. Field emission scanning electron microscopy (FESEM) with energy-dispersive X-ray spectroscopy confirmed that the elemental composition of minerals were copper, phosphorus, and oxygen. Synchrotron-based X-ray absorption fine structure showed that the local structure around Cu atoms deposited on the mineral was almost identical to that of commercial copper (II) phosphate Cu3(PO4)2∙3H2O. However, the crystallinity was low, and the structure was slightly distorted. Time profile analysis using FESEM revealed that copper phosphate mineralization was first apparent on Day 3 of adsorption, whereas mineral formation plateaued at around Day 7. It seems that mineralization occurs by the local saturation of phosphate and Cu2+ on the yeast cells. Mineralization of the rare earth ion Dy3+ was also demonstrated during long-term adsorption. Mineralization on phosphorylated yeast cells appears to follow a common path for various types of metal ions and provides a promising technique for metal recovery via irreversible adsorption