YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
135 巻, 6 号
選択された号の論文の11件中1~11を表示しています
誌上シンポジウム
  • 竹内 孝治, 畝山 寿之
    2015 年 135 巻 6 号 p. 761-762
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
  • 野村 政壽, 川原 佑太
    2015 年 135 巻 6 号 p. 763-767
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Type 2 diabetes is closely associated with our daily diets and has become a global health problem with increasing number of patients. Maintaining energy homeostasis is essentially required for the treatment of diabetes. Energy metabolism starts with taking in a meal. Nutrients including amino acids, fatty acids and glucose in the digest have been shown to act on the neuroendocrine cells in the gastrointestinal (GI) tract, and thereby play important roles in energy homeostasis. Therefore, the GI tract is now recognized as a sensor system for nutrient signals. Taste receptor type 1 member 2 (T1R2) is known to function as a co-receptor with T1R3 to detect sweet chemicals in the taste buds. It has been proposed that the T1R2/T1R3 receptor complex acts as sweet sensor in the intestine, and plays a pivotal role in sensing sugars and maintaining glucose homeostasis through incretin secretion. To clarify the physiological roles of T1R2 in glucose homeostasis, T1r2-lacZ knock-in/knock-out mice were generated. We found lacZ gene expression in the GI tract where T1r3 expression has been reported. Interestingly, the T1r2-lacZ knock-in mice showed impaired glucose tolerance on oral glucose challenge but not on intraperitoneal injection. However, the fasting glucose level in T1r2-lacZ knock-in mice was comparable to that in wild type mice. These results suggest an important role of the sweet taste receptor system in the intestine when stimulated by glucose. Therefore, the roles of T1R2 will be presented and the mechanism for metabolic homeostasis will be discussed.
  • 平澤 明
    2015 年 135 巻 6 号 p. 769-777
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Free fatty acids (FFAs) are not only essential nutritional components but they also act as signaling molecules in various physiological processes. A strategy to deorphanize G-protein-coupled receptors (GPCRs) identified a series of receptors for FFAs that play significant roles in nutrition regulation. In this free fatty acid receptor family, FFAR1 (GPR40) and FFAR4 (GPR120) are activated by long-chain FFAs. FFAR1 regulates insulin secretion in pancreatic β-cells, whereas FFAR4 promotes the secretion of glucagon-like peptide-1 (GLP-1) in the intestine, and also acts as a lipid sensor in adipose tissue to sense dietary fat and control energy balance. In this review, we discuss recent advances in the pharmacological characterization of FFAR1 and FFAR4, and we present a summary of current understandings of their physiological roles and their potential as drug targets.
  • 天ヶ瀬 紀久子, 中村 英志, 加藤 伸一, 竹内 孝治
    2015 年 135 巻 6 号 p. 779-782
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Monosodium glutamate (MSG) is known to provide the umami taste in the food. We have recently reported that glutamate has the potential to protect the small intestine against non-steroidal anti-inflammatory drugs (NSAIDs)-induced lesions in rats. In this paper, we examined this protective effect using sodium loxoprofen, one of the NSAIDs frequently used in Asian countries, to determine whether MSG accelerates the healing of loxoprofen-induced small intestinal lesions in rats. Loxoprofen at 60 mg/kg caused hemorrhagic lesions in the small intestine, mainly in the jejunum and ileum. These lesions spontaneously healed within 7 days, but this healing process was delayed by repeated administration of loxoprofen at low doses (10, 30 mg/kg) for 5 d after lesion induction. The healing-impairment action of loxoprofen was accompanied by the down-regulation of vascular endothelium-derived growth factor (VEGF) expression and an angiogenic response. The impaired healing caused by loxoprofen was significantly restored by co-treatment with a diet containing 5% MSG for 5 d, accompanied by the enhancement of VEGF expression and angiogenesis. We suggest that daily intake of MSG not only protects the small intestine against NSAIDs-induced damage but also exerts healing-promoting effects on these lesions.
  • 佐藤 しづ子, 笹野 高嗣
    2015 年 135 巻 6 号 p. 783-787
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Patients with dry mouth are increasing in Japan due to the country's super-aging society and stressful modern society. Dry mouth affects quality of life, including difficulty with speech or swallowing, and also causes aspiration pneumonia and, respiratory infection. Moreover, dry mouth closely relates to taste dysfunction, resulting in malnutrition, a common risk of nursing care in the elderly. Against these backgrounds, dry mouth has recently been a target of social concern. Drugs for dry mouth such as M3, a muscarinic agonist, have been widely used: however, these drugs have serious side effects, such as vomiting, sweating and/or digestive disorders. We examined the gustatory-salivary reflex to explore a remedy for dry mouth. We have demonstrated that umami stimulation increases saliva from both minor- and major salivary-glands, and that the effect is longer-lasting than with the other four basic tastes. Stimulating the umami response could therefore be a safe and useful remedy for dry mouth.
  • 水田 栄之助
    2015 年 135 巻 6 号 p. 789-792
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Individual taste sensitivity affects one's eating habits, and could thus play a role in the development of lifestyle-related diseases, such as obesity, hypertension and dyslipidemia. However, only a handful of studies have been conducted to investigate these associations. Therefore, we performed taste sensitivity tests on approximately 250 patients with lifestyle-related diseases who were undergoing outpatient treatment at the Department of Internal Medicine, or received a health check-up in order to examine the associations of individual taste sensitivity with their eating habits and lifestyle-related diseases. Our findings showed that sensitivity to sweet or salt taste was significantly lower in patients with cardiovascular diseases, and sensitivity to umami taste was significantly lower in obese patients. These findings suggest that taste sensitivity disorders may be linked not only to eating habits and lifestyle-related diseases, but also to the onset of cardiovascular diseases. Many of the drugs used in the treatment of lifestyle-related diseases and cardiovascular diseases, including antihypertensive agents, statins, fibrates, and allopurinol, are known to form zinc chelates and thereby possibly cause drug-induced taste disorders. Focusing on individual taste sensitivity to improve or maintain intake levels may become a new target for drug development in the areas of lifestyle-related and cardiovascular diseases.
総説
  • 野尻 宗子
    2015 年 135 巻 6 号 p. 793-808
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      The provision of health care frequently creates digitalized data such as hospital-based electronic data, medication prescription records, and claims data collectively termed “administrative database research”. The data source and analytical opportunities for study create risks that can lead to misinterpretation or bias the results. This review serves as an introduction to the concept of bias and confounding to help researchers conduct methodologically sound pharmacoepidemiologic research projects using administrative databases. Beyond general considerations for observational study, there are several unique issues related to database research that should be addressed. The risks of uninterpretable or biased results can be minimized by: providing a robust description of the data tables used; focusing on why and how they were created; measuring and reporting the accuracy of diagnostic and procedural codes used; and properly accounting for any time-dependent nature of variables. The hallmark of good research is rigorously careful analysis and interpretation. The promise for value of real world evidence using databases in medical decision making must be balanced against concerns related to observational inherited limitations for bias and confounding. Researchers should aim to avoid bias in the design of a study, adjust for confounding, and discuss the effects of residual bias on the results.
ノート
  • 菊池 千草, 松永 民秀, 鈴木 匡
    2015 年 135 巻 6 号 p. 809-820
    発行日: 2015/06/01
    公開日: 2015/06/01
    [早期公開] 公開日: 2015/03/13
    ジャーナル フリー
      Pharmacy school students were trained in a program simulating medication administration and giving adherence instructions. Following the training, the educational effects were evaluated. Students were separated into two groups. One group of students played the role of pharmacists and instructed simulated patients on medication adherence. Another group of students played the role of patients receiving simulated drug therapy; they were instructed on medication adherence by the students playing the role of pharmacists. The educational effects were evaluated using a questionnaire. The scores for “recognition of factors that influence medication adherence” tended to increase after the simulation, and they increased significantly after practical training. The scores for “self-evaluation of technique for instructing patients on medication adherence” increased significantly after the simulation, and they increased even more after practical training. The students' understanding of the effects on patients who were being instructed also increased significantly after the simulation, and these changes were maintained after practical training. In particular, students became more aware of the influence of pharmacists' attitudes. In practical training, the simulation training was helpful for bedside practice at hospital pharmacies and over-the-counter service at community pharmacies. Thus, the use of role play and simulated patients was an effective method for training pharmacy students to instruct patients on medication adherence.
  • 市村 祐一, 高松 宏行, 出内 秀樹, 小田 雅子, 武田 清孝, 齊藤 浩司
    2015 年 135 巻 6 号 p. 821-828
    発行日: 2015年
    公開日: 2015/06/01
    ジャーナル フリー
      Uremic toxins (UTs) accumulate in the body of hemodialysis patients. UTs often exert unfavorable effects on patients and cause significant interactions with clinically relevant drugs. In this study, we assayed plasma concentrations of three typical anionic UTs, indoxyl sulfate (IS), 3-indoleacetic acid (IA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), in 20 hemodialysis patients and 5 healthy volunteers. Moreover, the effects of these anionic UTs on the binding of pravastatin to human serum albumin (HSA) were also evaluated. CMPF concentrations in the plasma of patients were unchanged before and after dialysis (63.0±6.3 μM and 65.1±6.7 μM, respectively), and these values were about 5-fold greater compared with those in healthy volunteers. Although dialysis decreased the plasma IS concentration from 157.9±19.9 μM to 103.8±13.3 μM, the value after hemodialysis was still ca. 27-fold greater than that in healthy volunteers. IA concentrations before and after hemodialysis were almost identical to those in healthy volunteers. There were no significant differences in the plasma concentrations of the three anionic UTs between male and female patients. The magnitude of protein binding was in the order CMPF>IS>IA, indicating that hemodialysis clearance of these anionic UTs was dependent on their protein binding capacities. The ability of IS to reduce pravastatin binding to HSA was much greater than that of CMPF. The present results suggest that statins bind to site II on HSA, and that their binding is modulated by IS when elevated in hemodialysis patients.
  • 菅原 隆文, 村上 礼隆, 植竹 宣江, 開 浩一
    2015 年 135 巻 6 号 p. 829-833
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      Recently, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been more frequently isolated from blood specimens than in the past. In this study we investigated a panel of therapeutic agents used to treat 37 patients with ESBL-producing E. coli bacteremia. Antimicrobial agents administered as definitive therapy displayed higher efficacy rates than when empiric therapy was administered (efficacy rates, 95.7% vs. 62.5%). The success rate of carbapenem was 95.8% (23/24) in patients with ESBL-producing E. coli bacteremia. In addition, the success rate of cefmetazole against ESBL-producing E. coli sensitive to this drug was 87.5% (7/8). In conclusion, patients at high risk of infection due to ESBL-producing E. coli should be empirically treated with carbapenem antibiotics. In addition, cefmetazole may be a treatment option for patients with ESBL-producing E. coli bacteremia.
  • 富田 隆, 後藤 英和, 吉村 勇哉, 坪内 良子, 中西 利恵, 小島 千賀子, 米島 美穂子, 吉田 正, 田中 勝也, 住谷 賢治, ...
    2015 年 135 巻 6 号 p. 835-840
    発行日: 2015/06/01
    公開日: 2015/06/01
    ジャーナル フリー
      It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of the immersed tablets were lower than those of non-immersed tablets in vitro. Furthermore, components that constitute the food thickener and differences in composition concentrations differentially affect the disintegration and solubility of magnesium oxide tablets. This suggests that commercially available food thickeners are likely to be associated with changes in the degradation of magnesium oxide tablets, and they therefore should be carefully used in certain clinical situations.
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