薬理と治療
Volume 46, Issue 2, 2018
Volumes & issues:
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扉・目次
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TOPICS 第17 回CRC と臨床試験のあり方を考える会議 2017 in 名古屋
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- 受賞演題
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治験に特化した大規模災害対応マニュアルの作成─実施医療機関 / 治験依頼者連携 治験の効率向上PJ(ISEI-PJ)
46巻2号(2018);View Description Hide Description -
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ORIGINAL ARTICLES
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トラボプロスト/チモロールマレイン酸塩配合点眼液(デュオトラバ® 配合点眼液)の日常診療下における長期使用時の安全性と有効性―特定使用成績調査の最終解析結果報告―
46巻2号(2018);View Description Hide Description目的トラボプロスト╱チモロールマレイン酸塩配合点眼液(デュオトラバ(R) 配合点眼液,以下,本剤)の日常診療下における長期使用時の安全性および有効性を確認するために,特定使用成績調査(以下,本調査)を実施した。方法緑内障,高眼圧症の患者を対象に中央登録方式で登録し,2011 年3 月~2015 年2 月のあいだで本調査を実施した。1 例あたりの標準的な観察期間(使用期間)は24 ヵ月間であり,安全性についてはおもに副作用の発現状況を評価するほか,六つの重点調査項目を設定し収集した。有効性については有効率および眼圧下降により評価した。結果本調査における安全性解析対象症例は881例,有効性解析対象症例は873 例であった。副作用発現症例率は27.8%(245╱881 例)で,器官別大分類別でみると眼障害がもっとも多く,23.0%(203╱881 例)を占めた。おもな副作用として多毛症(眼周囲)78 件,眼瞼色素沈着66 件,点状角膜炎45件,眼充血39 件,虹彩色素過剰37 件,結膜充血32件などが認められた。一方,全体の有効率は83.0%(717╱864 例)であった。有効性解析対象例全体および新規単独投与症例のいずれにおいても,投与1 ヵ月後から投与24 ヵ月後までのすべての観察時点で投与前とくらべて眼圧は有意に下降した(すべての観察時点でP<0.0001)。結論本調査の結果から,日常診療下における本剤の長期使用時の安全性および有効性が示された。 -
継続的なアルギニン,アラニン,フェニルアラニン混合物投与と運動負荷の併用が,糖尿病モデルラットの血糖関連指標に及ぼす影響
46巻2号(2018);View Description Hide DescriptionBackground Our earlier reports have indicated that pre-exercise ingestion of an amino acid mixture composed of arginine, alanine, and phenylalanine(A-mix) increases levels of blood ketone bodies during exercise by increasing secretion of glucagon in overweight humans. Although these results suggest A-mix supplementation enhances lipolysis during exercise, acute stimulation of glucagon secretion may impair the health of diabetic patients. They cannot regulate glucagon secretion due to insulin resistance and╱or insulin deficiency, which might lead to the abnormally elevated blood levels of glucose and hemoglobinA1c(HbA1c). Herein, we carry out the long-term effect of A-mix with exercise in a rat model of type 2 diabetes and obesity on blood glucose level. Methods Male Zucker diabetic fatty(ZDF)rats underwent swimming exercise(3 days╱week) with(n=5)or without(n=5)A-mix supplementation(1 g╱kg body weight╱day)over a 5-week period. Results There were no difference in body weight, food intake, blood levels of glucose, HbA1c, insulin, glucagon, weights of liver, soleus, plantaris, gastrocnemius, epididymal and mesenteric fat. Although A-mix group exhibited significantly higher blood level of ketone bodies compared to control group at week 1, there were no difference at week 2 and later between two groups. Conclusions These results suggest that continuous supplementation of A︱mix(1 g╱kg body weight╱day)combined with exercise does not elevate the levels of casual blood glucose nor HbA1c in a rat model of type 2 diabetes and obesity. -
人参養栄湯はドパミンD2受容体を介して新規アパシー様モデルマウスにおける食欲不振ならびに巣作り行動低下を改善する
46巻2号(2018);View Description Hide DescriptionBackground The present study was conducted to investigate effect of ninjinyoeito on the motivation of orexigenic or nesting behaviors in repeated water immersed(WI)mice. Methods Ninjinyoeito(NYT, 1.5 g╱kg, PO)or with co-administration of dopamine D2 receptor antagonist(metoclopramide, 10 mg╱kg, IP)was administered to repeated WI model mice. We measured 1, 4, 8, and 24︱h cumulative food intake, 24-h nesting score, and used nest materials following final WI. In addition, effects of ingredients in NYT on dopamine metabolism-related enzymes were determined in the in vitro assay. Results WI resulted in a decrease in 4, 8, 24-h cumulative food intake, 24-h nesting score, and used nest materials. Additionally, the reduced food intake and nesting behavior by WI were increased by administrating NYT. The effect of NYT on food intake and nesting score was completely abolished with co-administration of dopamine D2 receptor antagonist and attenuated in pair-fed mice that was restricted to food intake of WI treated control mice. Moreover, monoamine-oxidase B inhibitory action by calycosin(IC50;3.17μmol╱L), catechol-O-Methy-transferase inhibitory action by onjixanthone II(IC50;1.02μmol╱L), or dopamine transporter inhibitory action by onjisaponin B(IC50;1.16μmol╱L)was found using in vitro assay. Conclusion Our results indicated that administration of NYT to repeated WI mice prevented the decrease in motivation of goal-directed behaviors in this model via dopamine D2 receptor activation. -
Effects of Long Pepper Extract on Peripheral Coldness in Japanese Healthy Women―A Randomized Double—blind Placebo—controlled Crossover Trial―
46巻2号(2018);View Description Hide DescriptionObjective Peripheral coldness can sometimes be unbearable, and may be associated with decreased peripheral blood flow. Because long pepper extract is known to improve blood flow, it might be a useful approach in the treatment of peripheral coldness. However, clinical data regarding the effects of long pepper extract on peripheral coldness are lacking. The objective of the present study was to assess the effects of long pepper extract on peripheral coldness in healthy women. Methods Thirty healthy women aged 20-64 years completed this randomized, double-blind, placebo-controlled, crossover trial. The primary endpoint was assessment of peripheral blood flow and skin temperature after cold water stress. This trial was registered at UMIN Clinical Trials Registry as UMIN000025893. Results All subjects completed this study without abnormal events regarding subjective and objective symptoms during the observation period. Peripheral blood flow and skin temperature were statistically significantly higher after cold water stress with consumption of long pepper extract than with consumption of placebo. Conclusion Our data suggest that a single oral intake of long pepper extract increases the peripheral blood flow and skin temperature after cold stress, and is a potential tool for the prevention and improvement of peripheral coldness in healthy women. -
Effect of Amla(Emblica officinalis Gaertn.)Extract Ingestion on Recovery of Body Temperature and Blood Flow Following Cold Stress―A Randomized Double—blind Placebo—controlled Study―
46巻2号(2018);View Description Hide DescriptionObjectives The aim of this study was to evaluate the efficacy of water-extracted amla-containing supplement on recovery of body surface temperature and blood flow following cold water stress in female subjects sensitive to cold temperature. Methods Volunteers(32 subjects)were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Subjects ingested amla extract-containing supplement(0.8 mg corilagin)or a placebo supplement. Recovery of body surface temperature and blood flow following cold water stress was compared 2 hours following supplement ingestion. Results As a result of validation on crossover design, the effect of testing period was not statistically significant, although the effect of the order had a tendency to differ. The intake of amla extract-containing test supplement resulted in a significant increase in body surface temperature and blood flow compared to the placebo group when evaluated in test period I. Conclusions The ingestion of amla extract-containing supplement accelerated recovery of body surface temperature and blood flow following cold water stress. This result suggested that the amla water extract may be a useful supplement for subjects who ordinarily feel “hie” -
変形性膝関節症の大腿四頭筋訓練における茶カテキン摂取併用効果の検討―ランダム化プラセボ対照二重盲検並行群間比較試験―
46巻2号(2018);View Description Hide Description変形性膝関節症(膝OA)の大腿四頭筋訓練における茶カテキン併用効果を検討した。膝OA 患者27名を無作為にカテキン併用群(Q‒C 群)と対照群(Q‒P 群)に分け12 週間の介入を行った。その結果,大腿四頭筋力は両群で増加し群間に差はなかったが,歩行機能であるtime up and go test(TUG)は初期膝OA においてQ‒C 群で有意な短縮を認め,カテキン摂取による神経‒筋機能改善への影響が示唆された。 -
乾燥肌の健常な成人女性におけるグルコラファニン含有ケール青汁の肌状態に対する有用性―ランダム化二重盲検プラセボ対照並行群間比較試験―
46巻2号(2018);View Description Hide DescriptionObjective Kale has been used as a health food and beverage. Cruciferous vegetables such as kale are known to decrese risk of cancer and glucosinolates were focused on effective components. The present study investigated the effects of kale containing glucoraphanin on subjects with skin dryness. Furthermore, it was evaluated whether glucoraphanin and metabolite (sulforaphane) enhance to produce collagen and hyaluronic acid in vitro. Methods In clinical study, randomized, double-blind, placebo-control, parallel-group study was conducted. 44 healthy Japanese female subjects aged 30-59 years were randomly assigned to kale group(kale containing 20 mg glucoraphanin)or placebo group. Skin moisture content, transepidermal water loss(TEWL), color difference, visual judgment by medical specialist and visual analogue scale(VAS)were performed for evaluation of skin condition. In vitro study, collagen and hyaluronic acid were determined using ELISA in normal human dermal fibroblasts treated with glucoraphanin or sulforaphane. Results In clinical study, skin moisture content was significantly increased after 12 weeks only in kale group. Regarding with the visual judgment by medical specialist, dryness was significantly improved in kale group compared to that in placebo group. Also, VAS score showed greater improvement in kale group than placebo group. In addition, there were no adverse clinical events throughout the study period. In vitro study, glucoraphanin and sulforaphane significantly enhanced to produce collagen and hyaluronic acid. Conclusion These results suggest that daily intake of kale containing glucoraphanine could improve skin moisture content and awareness of skin condition. Furthermore, glucoraphanin and sulforaphane may be effective to recover dermal function. -
健常成人におけるS—アリルシステインおよびアリインの吸収―にんにく卵黄粉末とにんにく粉末との比較―
46巻2号(2018);View Description Hide DescriptionObjective The aim of this study was to investigate the absorbability of S-Allylcysteine(SAC)and alliin after consumption of powdered garlic yolk in comparison with consumption of powdered garlic. Methods A randomized, parallel-group study was conducted with 14 healthy male subjects aged from 20 to 64 years. Subjects consumed 3.5 g of yolk garlic powder or garlic powder (each of the test foods contained 5 mg of SAC and 33 mg of alliin), and their blood levels of SAC and alliin were determined for 8 h after test food consumption. Results The crossover design was appropriate with respect to area under the blood concentration-time curve from 0 to 8 h calculated for the difference in SAC or alliin level from baseline level(ΔAUC0-8 h). ΔAUC0-8 h for SAC was 3346±654 ng╱mL・h in the garlic powder consumption period and 3598±584 ng╱mL・h in the garlic yolk consumption period(P<0.01). ΔAUC0-8 h for alliin was 3012±717 ng╱mL・h in the garlic powder consumption period and 3313±543 ng╱mL・h in the garlic yolk consumption period(P<0.01). Conclusions The absorbability of both SAC and alliin was good when taken as garlic yolk compared to consumption as garlic powder. -
加水分解度の異なる豚皮由来コラーゲンの吸収性比較評価―非盲検クロスオーバー試験―
46巻2号(2018);View Description Hide DescriptionObjective This study was conducted to assess the effect of hydrolysis level of collagen on its absorption. Methods An open-label, three-treatment cross over study was conducted in 7 healthy adult volunteers. All subjects received the following 3 types of porcine skin collagen test meals at the same dose(1.3 g)of hydroxyproline(Hyp):drink containing collagen hydrolysates(average molecular weight of 2500), gelatin powder, and porcine skin snack. Sequential plasma samples were collected up to 3 hours after ingestion, and measured plasma concentration of total, free, and peptide form Hyp. Results The plasma concentrations of Hyp were elevated in all groups. However, the significant differences were observed in the plasma concentrations and the area under the plasma concentration curves(AUCs)among the groups. The plasma concentration of total Hyp was elevated and reached the maximum concentration the fastest after the collagen hydrolysates ingestion. The AUC0-3h of total, free, and peptide form Hyp of the collagen hydrolysate and gelatin group were significantly higher than that of the porcine skin snack group, and AUC0-1h of total and free Hyp of the collagen hydrolysate group was significantly higher than that of the other groups. Furthermore, the ratio of peptide form Hyp to total Hyp tended to be high in order of the collagen hydrolysate, gelatin, porcine skin snack. Conclusion We concluded that collagen absorption depends on the hydrolysis level of it and that collagen hydrolysates are absorbed more rapidly than gelatin and conventional foods. -
軽度肥満者における体重,BMI および体脂肪量に対する甘草由来フラボノイドオイルの影響―健常被験者と肥満症被験者での層別解析について―
46巻2号(2018);View Description Hide DescriptionBackground The effects of licorice flavonoid oil(LFO)at a daily oral dose of 300 mg for 12 weeks on body weight, body mass index(BMI), and body fat mass in overweight subjects were evaluated in a randomized, double-blind, placebo-controlled study as reported by Tominaga et al in 2006. Stratified analysis was performed on the same subjects to determine whether there is a difference in the effects of LFO between healthy and obese subjects. Methods Subjects classified as healthy had a BMI of 24-30 and visceral fat area smaller than 100 cm2, while obese subjects had a BMI of 24-30 and visceral fat area larger than 100 cm2, according to the criteria for obesity defined by the Japan Society for the Study of Obesity. Next, stratified analysis was performed according to the presence or absence of obesity, calculating statistical significance of the effect of LFO on body weight, BMI, and body fat mass. Results Visceral fat areas in obese subjects were 1.43-1.49-fold higher than in healthy subjects, while body weight, BMI, and body fat mass in obese subjects were 1.05-1.19-fold higher than in healthy subjects. In healthy subjects, changes from baseline in body weight and BMI, as well as body fat mass in the LFO group, were significantly different or tended to decrease compared to those in the control group, while little or no effects of LFO on these parameters were observed in obese subjects. Conclusions LFO had more evident suppressive effects on body weight, BMI and body fat mass in healthy subjects than in obese subjects.
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INFORMATION
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CONSORT 2010声明-ランダム化並行群間比較試験報告のための最新版ガイドライン-(薬理と治療2010;38:939-49. より再掲載)
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臨床試験を報告するための指針−CONSORT 声明に準拠して論文を執筆するための15 項目(薬理と治療2017; 45: 339-44. より再掲載)
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