薬理と治療
Volume 40, Issue 8, 2012
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扉・目次
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TOPICS:第11回CRCと臨床試験のあり方を考える会議 2011 in 岡山
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- シンポジウム1 /多様化する臨床研究支援への取り組み- CRC のアイデンティティとは-
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【講演2】 これからの“リサーチナースのあり方”-名大病院化学療法部に所属する臨床研究コーディネーターの経験から学んだこと-
40巻8号(2012);View Description Hide Description -
- パネルディスカッション1 /臨床試験におけるコミュニケーションについて考える-よりよいチームアプローチを目指して-
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【講演2】 臨床試験関係者のためのコミュニケーション教育プログラム-「治験同意説明場面」を題材としたロールプレイ研修-
40巻8号(2012);View Description Hide Description -
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SERIES 臨床の現場から①
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ORIGINAL ARTICLES
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オステオポンチンの機能に及ぼすヒスタミン H1受容体拮抗薬の効果
40巻8号(2012);View Description Hide Description[Objectives The influence of histamine H1 receptor antagonists on the function of osteopontin(OS)was examined in vitro. We also examined the influence of epinastine hydrochloride (EP)on the appearance of OS in nasal secretions obtained from Japanese cedar pollinosis patients treated with EP during the pollen season. Methods BEAS-2B cells(5×105 cells/mL)were stimulated with 100 ng/mL TNF-α in the presence of various concentrations of histamine H1 receptor antagonists, fexofenadine hydrochloride(FEX), EP, azelastine hydrochloride(AZ)and ketotifen fumarate salt(KET)for 24h. OS levels in culture supernatants were examined by ELISA. BEAS-2B cells were also stimulated with 330 ng/mL OS in the presence of either FEX, EP, AZ or KET. After 24 h, the levels of cytokines, INF-γ, IL-4 and IL-5 in the culture supernatants were examined by ELISA. Nasal secretions were obtained from pollinosis patients treated with EP once a day at a single dose of 20 mg for two weeks. OS levels in nasal secretions were also examined by ELISA. Results The addition of histamine H1 receptor antagonists into BEAS-2B cell cultures caused significant suppression of OS production from cells induced by TNF-α stimulation. Histamine receptor antagonists examined in this study also inhibited the ability of BEAS-2B cells to produce IL-4 and IL-5, but not INF-γ, in response to OS stimulation. The minimum concentration that caused significant suppression of OS and cytokine production was nearly identical to their therapeutic blood levels. Oral administration of EP into pollinosis patients also inhibited OS concentrations in nasal secretions. Conclusions These results may suggest that histamine H1 receptor antagonists modulates the function of OS, and exerts therapeutic effects on allergic diseases, especially pollinosis., Objectives The influence of histamine H1 receptor antagonists on the function of osteopontin(OS)was examined in vitro. We also examined the influence of epinastine hydrochloride (EP)on the appearance of OS in nasal secretions obtained from Japanese cedar pollinosis patients treated with EP during the pollen season. Methods BEAS-2B cells(5×105 cells/mL)were stimulated with 100 ng/mL TNF-α in the presence of various concentrations of histamine H1 receptor antagonists, fexofenadine hydrochloride(FEX), EP, azelastine hydrochloride(AZ)and ketotifen fumarate salt(KET)for 24h. OS levels in culture supernatants were examined by ELISA. BEAS-2B cells were also stimulated with 330 ng/mL OS in the presence of either FEX, EP, AZ or KET. After 24 h, the levels of cytokines, INF-γ, IL-4 and IL-5 in the culture supernatants were examined by ELISA. Nasal secretions were obtained from pollinosis patients treated with EP once a day at a single dose of 20 mg for two weeks. OS levels in nasal secretions were also examined by ELISA. Results The addition of histamine H1 receptor antagonists into BEAS-2B cell cultures caused significant suppression of OS production from cells induced by TNF-α stimulation. Histamine receptor antagonists examined in this study also inhibited the ability of BEAS-2B cells to produce IL-4 and IL-5, but not INF-γ, in response to OS stimulation. The minimum concentration that caused significant suppression of OS and cytokine production was nearly identical to their therapeutic blood levels. Oral administration of EP into pollinosis patients also inhibited OS concentrations in nasal secretions. Conclusions These results may suggest that histamine H1 receptor antagonists modulates the function of OS, and exerts therapeutic effects on allergic diseases, especially pollinosis.] -
Ⅱb 型高脂血症を伴う 2 型糖尿病患者においてフェノフィブラートとスタチン低用量の併用療法は中性脂肪/レムナントと LDL を効果的に低下させる
40巻8号(2012);View Description Hide Description[Hypertriglyceridemia has been recognized as an independent risk factor for atherosclerosis. Increased plasma remnant lipoproteins underlie ypertriglyceridemia. Remnant lipoproteins are atherogenic since they are TG-rich and cholesterol-rich, and therefore cause cholesterol accumulation in the plaque of artery. Dyslipidemia in type 2 diabetic patients is characterized by increased plasma triglyceride(TG), remnant lipoprotein and LDL. The correction of increased plasma levels of both TG and LDL is very important to prevent atherosclerosis in type 2 diabetic patients. Fibrate decreases mainly plasma TG and renmnat lipoproteins, whereas statin decreases mainly plasma LDL. The combination therapy of fibrate and statin is therefore thought to be very effective for the correction, but little information is available in Japan. In this study we investigated the effect of the combination therapy on dyslipidemia, glycemic control and adverse reactions in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia). Twenty two diabetic patients were studied. They were under 65 years old. They had type Ⅱb hyperlipidemia, i. e. increased plasma levels of TG(≧150 mg/dL)and LDL-cholesterol (≧120 mg/dL). They had normal renal function(plasma creatinine level<1.1 mg/dL)and normal liver function. Plasma lipid and remnant cholesterol were measured before and after the treatment. Plasma remnant cholesterol was determined as RLP-cholesterol(normal range <5.2 mg/dL)by the method of Nakajima et al. The combination therapy of fenofibrate and low dose statin over 10 months significantly reduced plasma TG by 62.3%(281→106 mg/dL), plasma LDL-cholesterol by 35.5%(166→107 mg/dL), and plasma remnant cholesterol by 60.1% (11.2→4.7 mg/dL), and raised plasma HDL-cholesterol by 15.0%(46→53 mg/dL). The combination therapy tended to reduce HbA1c(6.9→6.6%). Plasma CPK and creatinine levels were not changed before and after the treatment and no adverse reaction were observed over the study period. It is concluded that combination therapy of fenofibrate and low dose statin is very effective to reduce particularly plasma TG and remnant cholesterol as well as plasma LDL-cholesterol in diabetic patients. The combination therapy should be positively considered in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia)if they have normal renal function., Hypertriglyceridemia has been recognized as an independent risk factor for atherosclerosis. Increased plasma remnant lipoproteins underlie ypertriglyceridemia. Remnant lipoproteins are atherogenic since they are TG-rich and cholesterol-rich, and therefore cause cholesterol accumulation in the plaque of artery. Dyslipidemia in type 2 diabetic patients is characterized by increased plasma triglyceride(TG), remnant lipoprotein and LDL. The correction of increased plasma levels of both TG and LDL is very important to prevent atherosclerosis in type 2 diabetic patients. Fibrate decreases mainly plasma TG and renmnat lipoproteins, whereas statin decreases mainly plasma LDL. The combination therapy of fibrate and statin is therefore thought to be very effective for the correction, but little information is available in Japan. In this study we investigated the effect of the combination therapy on dyslipidemia, glycemic control and adverse reactions in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia). Twenty two diabetic patients were studied. They were under 65 years old. They had type Ⅱb hyperlipidemia, i. e. increased plasma levels of TG(≧150 mg/dL)and LDL-cholesterol (≧120 mg/dL). They had normal renal function(plasma creatinine level<1.1 mg/dL)and normal liver function. Plasma lipid and remnant cholesterol were measured before and after the treatment. Plasma remnant cholesterol was determined as RLP-cholesterol(normal range <5.2 mg/dL)by the method of Nakajima et al. The combination therapy of fenofibrate and low dose statin over 10 months significantly reduced plasma TG by 62.3%(281→106 mg/dL), plasma LDL-cholesterol by 35.5%(166→107 mg/dL), and plasma remnant cholesterol by 60.1% (11.2→4.7 mg/dL), and raised plasma HDL-cholesterol by 15.0%(46→53 mg/dL). The combination therapy tended to reduce HbA1c(6.9→6.6%). Plasma CPK and creatinine levels were not changed before and after the treatment and no adverse reaction were observed over the study period. It is concluded that combination therapy of fenofibrate and low dose statin is very effective to reduce particularly plasma TG and remnant cholesterol as well as plasma LDL-cholesterol in diabetic patients. The combination therapy should be positively considered in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia)if they have normal renal function.] -
Bifidobacterium animalis subsp. lactis GCL2505 を含有する発酵乳の摂取による便秘傾向を有する健常成人の排便回数,便性状,および糞便菌叢の改善
40巻8号(2012);View Description Hide Description[The aim of this study was to evaluate the changes in intestinal bifidobacteria and the effect on fecal properties in healthy subjects with mild constipation after administration of a fermented milk containing Bifidobacterium animalis subsp. lactis(B. lactis)GCL2505. Volunteers(n=62;15 male, 47 female;42.5±10.2 years[mean±SD])were randomly divided into two groups and given 100 g of fermented milk containing B. lactis GCL2505(>1×107cfu/g)or a placebo daily for 2 weeks in a double-blind crossover study. An increase in the number of total bifidobacteria(sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescentis, B. angulatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis, and B. lactis)was detected in feces after administration of the B. lactis GCL2505 fermented milk by species- and subspecies-specific real-time polymerase chain reaction analysis. The number of endogenous bifidobacteria species, excluding B. lactis, remained unchanged, and B. lactis became the predominant bifidobacterial species. Defecation frequency and stool quantity increased significantly(p<0.05)during the B. lactis GCL2505 fermented milk ingesting period compared with placebo. These results indicate that GCL2505-fermented milk contributes to an increase in intestinal bifidobacteria by proliferating itself and to improvements in mild constipation without affecting endogenous bifidobacteria., The aim of this study was to evaluate the changes in intestinal bifidobacteria and the effect on fecal properties in healthy subjects with mild constipation after administration of a fermented milk containing Bifidobacterium animalis subsp. lactis(B. lactis)GCL2505. Volunteers(n=62;15 male, 47 female;42.5±10.2 years[mean±SD])were randomly divided into two groups and given 100 g of fermented milk containing B. lactis GCL2505(>1×107cfu/g)or a placebo daily for 2 weeks in a double-blind crossover study. An increase in the number of total bifidobacteria(sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescentis, B. angulatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis, and B. lactis)was detected in feces after administration of the B. lactis GCL2505 fermented milk by species- and subspecies-specific real-time polymerase chain reaction analysis. The number of endogenous bifidobacteria species, excluding B. lactis, remained unchanged, and B. lactis became the predominant bifidobacterial species. Defecation frequency and stool quantity increased significantly(p<0.05)during the B. lactis GCL2505 fermented milk ingesting period compared with placebo. These results indicate that GCL2505-fermented milk contributes to an increase in intestinal bifidobacteria by proliferating itself and to improvements in mild constipation without affecting endogenous bifidobacteria.]
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