薬理と治療
Volume 42, Issue 7, 2014
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扉・目次
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TOPICS
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健康的な食生活の実現に向けた機能性を持つ農林水産物・食品の開発プロジェクト
42巻7号(2014);View Description Hide Description農林水産省では,国民の豊かな食生活に寄与するべく,機能性を持つ農産物・加工品の開発やデータベースの構築,機能性食品の提供システムに関する研究を進めている。平成24年度からスタートした「機能性を持つ農林水産物・食品の開発プロジェクト」で中心的な役割を担っている独立行政法人農研機構食品総合研究所の山本(前田)万里氏(食品機能研究領域長)に,機能性農産物の開発プロセスやデータベース構築などの実際についてうかがった(編集部)。
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TOPICS:第13 回CRC と臨床試験のあり方を考える会議 2013 IN 舞浜
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- シンポジウム4 /これからのモニタリングについて考えよう!
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ORIGINAL ARTICLES
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Experimental Conditions Affecting the Contracture of the Rat Soleus and Relief Effect of Lutein on the Contracture
42巻7号(2014);View Description Hide DescriptionMuscle contractile force by the electrical stimulation or drug has been used as a useful experimental parameter. In this study, we measured the change of the tonus as an index of the contracture of the rat soleus after electrical field stimulation in vitro. The experimental conditions affecting on the contracture, such as the difference between the right and left soleus, the role of oxygen and D︱glucose, and the effects of lutein and astaxanthin, were evaluated. The contracture increased in course of time after electrical field stimulation(10 mV, 1 Hz, duration:0.1 msec). Significant difference of the contracture was observed between the right and left soleus. By changing oxygen to nitrogen or changing D ︱glucose to 2︱deoxy︱D︱glucose, the contracture was significantly and markedly augmented, respectively. By the pre︱treatment with lutein(100 mg╱kg, p.o.), the contracture was significantly attenuated, but not by astaxanthin as compared with control. These results show that there is the right and left difference and that glucose and oxygen play important roles to maintain the tonus of the soleus. Moreover, lutein was useful to relief the muscle contracture. Antioxidant effect may not be involved in this relieving effect by lutein, because astaxanthin did not show efficacy. -
CLP 誘発ラット敗血症モデルにおける播種性血管内凝固症候群(DIC)および臓器障害に対するThrombomodulin alfa の作用
42巻7号(2014);View Description Hide DescriptionDisseminated intravascular coagulation(DIC)associated with sepsis is a serious clinical condition that is characterized by activation of coagulation and widespread microvascular thrombosis resulting in multiple organ failure. In this study, we examined the effects of thrombomodulin alfa(TM alfa)on DIC and organ injury caused by sepsis in a cecal ligation and puncture(CLP)model in rats. In the first study, rats were treated with 3 mg╱kg of TM alfa at 1 hour after CLP operation. After 9 hours of CLP, blood was collected. In the second study, rats were treated with antibiotics:imipenem︱cilastatine sodium(IPM╱CS, 10 mg╱kg)and with or without TM alfa(3 mg╱kg)at 1 hour and 3 hours after CLP, respectively. After 12 hours of CLP, blood was collected. Platelet count(PLT)and plasma level of several parameters including high mobility group box︱1(HMGB ︱1), alanine aminotransferase(ALT)and blood urea nitrogen(BUN)were measured. TM alfa significantly suppressed the changes of PLT, ALT and HMGB ︱1, but not of BUN. The combination therapy with TM alfa and IPM╱CS markedly suppressed changes of PLT, HMGB︱1, ALT and BUN compared with TM alfa monotherapy. These results suggest that TM alfa monotherapy is effective for DIC and organ injury associated with sepsis. Furthermore, the combination therapy with TM alfa and antibiotics exerts further beneficial effects on DIC and organ injury associated with sepsis. -
変形性膝関節由来滑膜細胞の一酸化窒素(NO)産生に及ぼすグルコサミンの効果
42巻7号(2014);View Description Hide DescriptionObjective The present study was designed to examine the influence of glucosamine hydrochloride(GH)on the ability of synoviocytes to produce nitric oxide(NO), which is the important effector molecule in the development of osteoarthritis, in response to osteopontin(OPN)stimulation in vitro. Methods Synoviocytes(5⊠105 cells╱mL)derived from osteoarthritis patients were stimulated with 330 ng╱mL OPN in the presence of various concentrations of GH for 24 hours. The levels of NO in culture supernatants was examined by NO2╱ NO3 assay kits. To examine the influence of GH on transcription factor, NF︱κB, activation and iNOS mRNA expression, synoviocytes (5×10 5 cells╱mL)were also cultured in a similar manner for 4 and 12 hours, respectively. The levels of both mRNA expression and transcription factor activation were measured by ELISA. Results Addition of GH into cell cultures caused the suppression of OPN ︱induced NO production from synoviocytes. The minimum concentration that caused significant suppression of NO production was 1.0 mg╱mL. GH at more than 1.0 mg╱mL also inhibited iNOS mRNA expression and NF︱κB activation, which were increased by OPN stimulation in synoviocytes. Conclusion These results strongly suggest that GH favorably modify the clinical condition of osteoarthritis patients through the suppression of NO production from synoviocytes. -
2 型糖尿病219 例におけるアログリプチン12 ヵ月間投与の有効性と安全性
42巻7号(2014);View Description Hide DescriptionObjectives This retrospective study was undertaken to clarify the efficacy and safety of alogliptin. The characteristics of the patients in whom alogliptin exerts its HbA1c︱lowering effect fully were also explored. Methods Alogliptin was administered as initial, additive, or exchange medication to 219 type 2 diabetic patients. The primary efficacy endpoint was the change in HbA1c at 12 months after the start of alogliptin treatment. Results Administration of alogliptin significantly decreased HbA1c(7.79±0.96% at baseline→7.24±0.85 at 3 months →7.18±0.89% at 6 months→7.20±0.98% at 9 months→7.23±0.94% at 12 months;at all time points:P<0.0001 vs. baseline). There was no significant difference in ΔHbA1c(=HbA1c at 12 months-HbA1c at baseline)between patients who took other oral hypoglycemic agents(OHA)concomitantly and those who took alogliptin as the only OHA. There was no significant difference in ΔHbA1c with respect to the kind of oral hypoglycemic agents used concomitantly, either. Multiple logistic regression analysis indicated that factors that contributed to ΔHbA1c were baseline HbA1c and initial╱additive rather than exchange administration of alogliptin. ΔHbA1c was significantly, negatively correlated with baseline HbA1c value. There were no changes in clinical parameters thought to be adverse events. Conclusions Administration of alogliptin provided a significant and clinically relevant reduction in HbA1c. High baseline HbA1c value may predict a large effect of alogliptin. -
日本人2 型糖尿病患者におけるサキサグリプチンの有用性―多施設共同,無作為化,プラセボ対照二重盲検群間比較試験―
42巻7号(2014);View Description Hide DescriptionObjective Saxagliptin is a novel, potent and selective inhibitor of dipeptidyl peptidase︱4. We performed two multicentre, randomized, placebo︱controlled, double︱blind, clinical studies to assess the efficacy and safety of saxagliptin in Japanese patients with type 2 diabetes mellitus. Methods In a PhaseⅡ dose︱response study, a total of 350 subjects were administered saxagliptin 1mg(n= 93), 2.5 mg(n=88), or 5mg(n=82), or placebo(n=87)once daily for 12 weeks. In a PhaseⅡ╱Ⅲ trial, 279 subjects were treated with saxagliptin monotherapy 2.5mg(n=92), 5 mg(n=97)or placebo(n=90)once daily for 24 weeks. The primary efficacy endpoint in the two trials was the change in HbA1c levels from baseline. Results In the dose︱response study, saxagliptin 1 mg, 2.5 mg, and 5mg significantly reduced HbA1c levels compared with placebo(P<0.0001). The mean change in HbA1c at Week 12 from baseline was -0.08, -0.59, -0.69, and -0.90% in the placebo, saxagliptin 1 mg, 2.5mg and 5 mg groups, respectively. In the 24︱week trial, the reduction in HbA1c in the two saxagliptin monotherapy groups was significantly greater than that reported in the placebo group throughout the 24 weeks of treatment. The mean change in HbA1c at Week 24 from baseline was 0.27%, -0.25%, and -0.33% in the placebo, saxagliptin 2.5 mg and saxagliptin 5 mg groups, respectively. No clinically significant adverse events, including hypoglycemia, were observed in the two trials. Conclusion The results of these two studies confirmed that saxagliptin monotherapy was effective and well tolerated in the treatment of Japanese patients with type 2 diabetes. -
日本人2 型糖尿病患者におけるサキサグリプチンの長期単独療法および長期併用療法試験
42巻7号(2014);View Description Hide DescriptionObjective To assess the efficacy and safety of long︱term saxagliptin therapy, we conducted two phase Ⅲ, multicentre, open︱label studies. The first assessed its use as long︱term monotherapy and the second its use in combination with another oral anti︱diabetic agent(ODA). Methods In the long︱term monotherapy study, 125 subjects with type 2 diabetes were treated with saxagliptin 5 mg once daily for 52 weeks. In the long︱term combination study, a total of 577 subjects with poorly controlled type 2 diabetes on another ODA such as a sulfonylurea (SU), α︱glucosidase inhibitor(AGI), biguanide(BG), tiazolidinedione(TZD)or glinide (GN), were treated with saxagliptin 5 mg once daily for 52 weeks. Efficacy endpoints in these two studies were HbA1c and fasting plasma glucose (FPG)reductions from baseline. Results In the long︱term monotherapy study, HbA1c and FPG levels significantly decreased from Week 2, and the reductions were sustained throughout the 52︱week treatment period. The change in HbA1c with saxagliptin 5 mg at Week 52 from baseline(LOCF)was -0.46±0.08% (mean±SE). In the long︱term combination study, the number of subjects in each of the ODA sub︱groups was:SU(n=183), AGI(113), BG(116), TZD(108), and GN(57). Addition of saxagliptin to ODA therapy decreased HbA1c levels throughout the study in all the combination treatment groups. At 52 weeks, the changes in HbA1c from baseline for saxagliptin+SU, saxagliptin+AGI, saxagliptin+BG, saxagliptin+TZD, and saxagliptin+GN were -0.50 ±0.06%, - 0.83±0.09%, -0.64±0.09%, -0.51±0.10%, and -0.60±0.12%, respectively. In the monotherapy study, no clinically important adverse events were observed. Body weight was not significantly altered and no cases of hypoglycemia were documented. In the combination study, the incidence of hypoglycemia was approximately 10% in the saxagliptin+SU and saxagliptin+GN groups, but much lower in the saxagliptin+AGI and saxagliptinBG groups. Conclusion Long︱term saxagliptin monotherapy and combination therapy(with saxagliptin plus another ODA)produced sustained glycemic control for up to 52 weeks, and was well tolerated in Japanese patients with type 2 diabetes.
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