Volume 36,
Issue 12,
2008
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座談会
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響き合いネットワーク東京
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第10回医療コミュニケーションワークショップ(WS)
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薬理と治療 36巻12号, 1089-1093 (2008);
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ORIGINAL ARTICLES
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薬理と治療 36巻12号, 1097-1104 (2008);
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Objective The present study was carried out to examine the influence of clarithromycin(CAM)and its metabolites, M−1, M−4 and M−5 on interleukin(IL)−8 production in humanbronchial epithelial cells, BEAS−2B cells, in response to tumor necrosis factor(TNF)−αstimulation in vitro.Methods BEAS−2B cells(5×105 cells/mL)were stimulated with 5.0 ng/mL TNF−α in thepresence of various concentrations of either CAM, M−1, M−4 or M−5. The culture supernatantswere collected 24 hours after the start of cell culture, and IL−8 levels in the culturesupernatants were assayed by ELISA. We also examined IL−8 mRNA expression and nuclearfactor(NF)−κB activation in BEAS−2B cells by RT−PCR and ELISA, respectively.Results The addition of CAM at more than 0.4μg/mL was significantly suppressed the productionof IL−8 in BEAS−2B cells, when the agent was added 2 hours before(but not after)the start of TNF−α stimulation. Pretreatment of cells with M−4 and M−5, but not M−1,could also inhibit the production of IL−8. The minimum concentration of these agents, whichcaused a significant suppression was 0.04μg/mL and 0.1μg/mL, respectively. Further more,M−4 at more than 0.1μg/mL could suppress the ability of cells to produce IL−8 induced byTNF−α stimulation, even when the treatment of cells with agent was started 2 hours afterTNF−α stimulation. We then examined the influence of M−4 on NF−κB activation and IL−8mRNA expression in 2 hour−treated BEAS−2B cells. The addition of M−4 into cell culturecaused a significant suppression of NF−κB activation and IL−8 mRNA expression, when thecells were treated with the agent at 0.04μg/mL.Conclusion These results strongly suggest that metabolized materials of CAM, especiallyM−4 could suppress the IL−8 production through the inhibition of NF−κB activation and IL−8 mRNA expression, which were increased by TNF−α stimulation.(Jpn Pharmacol Ther 2008;36:1097−104)KEY WORDS Clarithromycin, Metabolized clarithromycin, Epithelial cells, IL−8, Suppression,in vitro
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薬理と治療 36巻12号, 1105-1118 (2008);
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Objective The purpose of the present study was to examine the influence of epinastine hydrochloride(EP), a second generation H1 receptor antagonist, on the function of monocytederived dendritic cells(MoDCs)in vitro. Methods MoDCs were differentiated from peripheral blood monocytes from healthy subjects with GM−CSF and IL−4. After LPS stimulation of MoDCs in the presence or absence of either EP or chlorpheniramine(CH), cell surface molecules(CD40, CD80 and CD86), as well as concentrations of TNF−α, IL−6, IL−12p35, IL−12p70 and IL−10 in culture supernatants, were examined by flow cytometer and ELISA, respectively. We also examined the influence of EP on the ability of MoDCs to stimulate allogeneic CD4+ T cells by examining T cell proliferation and cytokine(IL−4 and IFN−γ)secretion. Results EP significantly inhibited the up−regulation of cell surface marker, CD40, CD80 and CD86, expression on MoDCs induced by LPS stimulation. EP also suppressed the secretion of TNF−α, IL−6, IL−12p35, and IL−12p70, which were up−regulated by LPS stimulation, however, the secretion of IL−10 was not affected. Treatment of MoDCs with EP down−regulated both the allostimulatory function and the capacity to stimulate CD4+ T cells to secrete IL−4 and IFN−γ. Moreover, EP inhibits the down−regulation of fluorescein isothiocyanate− dextran uptake during DC maturation. In contrast, CH had little or no effect on DC maturation. Conclusion EP interferes the function of MoDCs and results in favorable modification of the allergic disease state.(Jpn Pharmacol Ther 2008;36:1105−18)KEY WORDS Dendritic cells, Co−stimulatory molecule, IL−10, IL−12, Epinastine hydrochloride
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薬理と治療 36巻12号, 1119-1122 (2008);
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The present study was undertaken to clarify the effect of fluticasone furoate(FF), anovel enhanced−affinity glucocorticoid, on ovalbumin−sensitised allergic rhinitis model inrats, and its efficacy and duration of action were compared with those of fluticasone propionate(FP)as the clinical standard. In actively sensitized rats, FF at doses of 0.1, 1 and 10μg,inhibited antigen−induced nasal rubbing and sneezing dose−dependently, with comparablepotency to FP at doses of 0.1, 1 and 10μg. The inhibitory effects of FF(10μg)on antigeninducednasal rubbing and sneezing were still sustained at 12 hours after intranasal administration,whereas the effect of FP(10μg)on sneezing had disappeared by 12 hours postdosing,demonstrating that FF has a longer duration of action than FP. These results suggest theutility of FF for the treatment of allergic rhinitis.(Jpn Pharmacol Ther 2008;36:1119−22)KEY WORDS Fluticasone furoate, Fluticasone propionate, Allergic rhinitis, Nasal symptoms,Rats
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薬理と治療 36巻12号, 1123-1129 (2008);
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Objectives The purpose of this study was to evaluate the skin permeability and analgesic/anti−inflammatory effects of a ketoprofen−containing tape and a loxoprofen sodium−containingtape.Methods For measurement of the skin permeability, skin specimens from hairless micewere mounted on the diffusion cells, and then, the receptor solution was collected every 2hours for 24 hours. The pharmacological effects of the both products were evaluated usingrat models of yeast−induced hyperalgesia, as an acute inflammation model, and, adjuvantinducedarthritis(AA)and collagen−induced arthritis(CIA), as chronic inflammation models,respectively. For yeast−induced hyperalgesia rats, the tapes were applied 1 hour or 3 hoursafter the injection of yeast, and for AA and CIA rats, those were applied for 24 hours a dayfor 7 days continuously after the induction of arthritis.Results In the skin permeability study, the cumulative amount of ketoprofen was higherthan those of loxoprofen and trans−OH loxoprofen. In the pharmacological studies, the bothproducts attenuated decrease of the paw−withdrawal threshold and increase of the paw swellingrate in each models. Moreover, the effects of the ketoprofen−containing tape were comparableto, or stronger than those of the loxoprofen sodium−containing tape.Conclusions These results suggest that the ketoprofen−containing tape and the loxoprofensodium−containing tape have analgesic and anti−inflammatory effects, and pharmacologicaleffects of the ketoprofen−containing tape are thought to be comparable to, or stronger thanthose of the loxoprofen sodium−containing tape. The ketoprofen−containing tape may be, atleast in part, more useful for inflammatory disorders with superior pharmacological efficacies,because of the higher skin permeability.(Jpn Pharmacol Ther 2008;36:1123−9)KEY WORDS Ketoprofen−containing tape, Loxoprofen sodium−containing tape, Skin permeability,Analgesic, Anti−inflammatory
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薬理と治療 36巻12号, 1131-1139 (2008);
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Aripiprazole 0.1% oral solution is a new formulation that was developed for easier swallowingby schizophrenia patients with dysphagia and for use in patients in whom treatmentusing a tablet formulation is difficult and compliance is unreliable, such as those who tend torefuse drug therapy because they cannot understand the necessity of taking the drug due totheir clinical state.The bioequivalence of 3 mL of aripiprazole 0.1% oral solution and one aripiprazole 3 mgtablet was evaluated by comparing the pharmacokinetics of the two formulations following singleoral administration in 22 healthy adult male subjects under a fasting condition in a 2−treatment,2−period, open−label crossover trial. A washout period of 35 days was set betweenstudy drug administration in PeriodsI and II.The 90% CI(confidence intervals)for the differences in the mean log−transformedAUC168h and Cmax values between 3 mL of aripiprazole 0.1% oral solution and one aripiprazole3 mg tablet were respectively log(0.99)to log(1.07)and log(0.97)to log(1.08). As bothwere within the bioequivalence criteria range of log(0.8)to log(1.25), it was judged that thetwo formulations were bioequivalent.All of the adverse drug reactions in this study have been reported as adverse drug reactionsfor aripiprazole in previous oral aripiprazole studies performed prior to this study inJapan. Aripiprazole 0.1% oral solution is therefore considered to pose no particular safetyproblems.No death or serious adverse events or clinically significant adverse events occurred.(Jpn Pharmacol Ther 2008;36:1131−9)KEY WORDS Aripiprazole, Atypical antipsychotics, Healthy adult male subjects, Oral solution,Bioequivalence
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薬理と治療 36巻12号, 1141-1158 (2008);
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To evaluate effects of glucosyl hesperidin−containing food on body weight and serum triglyceridelevels, a randomized, placebo−controlled, double−blind parallel group study wasconducted. The subjects were 93 non−lean[19 kg/m2≦body mass index(BMI)<30 kg/m2]and mildly hypertriglyceridemic(serum triglyceride≧120 mg/dL)adult volunteers consistingof 70 males and 23 females(average BMI:24.5±2.2 kg/m2, average triglyceride:181.4±60.5 mg/dL). Subjects were randomly divided into four groups:low dose group(250 mg/dayglucosyl hesperidin), medium dose group(500 mg/day), high dose group(1000 mg/day)andplacebo group. Each group was given appropriate amount of glucosyl hesperidin everyday for4 weeks. The result revealed that the body weight and body mass index(BMI)were significantlylowered in medium dose group(Abody weight;−0.59±0.93 kg(p<0.05), ABMI;−0.20±0.31 kg/m2(p<0.05)respectively at 4 weeks)compared to the values at 0 week. Thesignificant decrease of the body weight and BMI were also seen in high dose group. Also, thewaist circumference was significantly lowered or tended to be reduced in medium dose group(A−1.73±3.26 cm(p<0.1)at 2 weeks and A−2.30±3.79 cm(p<0.05)at 4 weeks). Theserum triglyceride levels showed no change in each group during the test period. No clinicallysignificant adverse events were observed in association with the intake of the testfoods. Thus the present observations suggest that the consecutive daily intake of glucosylhesperidin at 500 mg or more may reduce body weight in non−lean subjects.(Jpn Pharmacol Ther 2008;36:1141−58)KEY WORDS Glucosyl hesperidin, Body weight, Waist circumference, Triglyceride
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薬理と治療 36巻12号, 1159-1165 (2008);
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A double−blind crossover clinical study was conducted on 50 adults with mild constipationto examine the effects of AOJIRU drink powder of Angelica keiskei leaf containing indigestibledextrin on defecation. The subjects were mean age of 37.0±6.9 years. Each subjectwas given either AOJIRU drink powder of Angelica keiskei leaf containing indigestible dextrin(test drink)or placebo drink, 3 times a day for 2 weeks. The test drink contains 5.1 g of indigestibledextrin per day amount, while the placebo drink contains maltodextrin instead. As aresult, the subjects taking the test drink showed a significant increase in the defecation frequencyand the estimated fecal quantity compared to those taking the placebo drink(p<0.05). It was also confirmed that the test drink does not cause any adverse events. In conclusion,the administration of AOJIRU drink powder of Angelica keiskei leaf containing indigestibledextrin serves for improving the defecation in adults with mild constipation.(Jpn Pharmacol Ther 2008;36:1159−65)KEY WORDS AOJIRU drink powder of Angelica keiskei leaf,Indigestible dextrin,Defecationfrequency,Estimated fecal quantity
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薬理と治療 36巻12号, 1167-1176 (2008);
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We evaluated the safety of long−term or excessive intake of the oolong tea beverage containingindigestible dextrin. To evaluate the safety of long−term intake of the beverage(200mL)containing 6 g of indigestible dextrin, an open−label trial was conducted. 22 subjectswere given the test beverage 3 times a day with meal for 12 weeks. Also, to evaluate thesafety of excessive intake of the beverage, a placebo−controlled, double−blind parallel grouptrial was conducted. 36 subjects were randomly divided into two groups, and were given adouble volume(400 mL)of the test beverage or the placebo beverage 3 times a day with mealfor 4 weeks. The result indicated no clinically important change in physical examinations,blood tests, urine tests and clinical examination in both trials. Thus, these results demonstratedthe safety of the oolong tea beverage containing indigestible dextrin.(Jpn Pharmacol Ther 2008;36:1167−76)KEY WORDS Indigestible dextrin, Long−term intake, Excessive intake, Safety test
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薬理と治療 36巻12号, 1179-1188 (2008);
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Vitamin K is one of the nutritional elements which promote bone formation, and it is recommendedto take vitamin K to prevent osteoporosis. We evaluated the efficacy in bonemetabolism and safety of 12 weeks intake of vitamin K2(menaquinone−4:MK−4)containingcalcium tablets.Eighty−six healthy male and female volunteers were divided into two groups;onegroup took calcium tablets and the other group took vitamin K2 (MK−4)(1.5 mg/day)containingcalcium tablets for 12 weeks. In the vitamin K2(MK−4)containing calcium tablets takinggroup, γ−carboxylated osteocalcin(GlaOC)was increased and undercarboxylated osteocalcin(ucOC)was decreased in both female(before and after menopause)and male subjects, suggestingpromoted bone formation by vitamin K2(MK−4). There were no adverse events orclinically relevant changes in safety parameters during the 12 weeks of intake and follow−upperiod of successive 4 weeks.This study showed that the vitamin K2(MK−4)containing calcium tablets used in thisstudy is effective in improving bone metabolism safely, and is effective in preventing osteoporosis.(Jpn Pharmacol Ther 2008;36:1179−88)KEY WORDS Vitamin K2,Calcium,Osteocalcin,Bone formation,Osteoprosis
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薬理と治療 36巻12号, 1189-1195 (2008);
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Vitamin K is known as a nutrient to promote bone formation, and there are some foodproducts containing vitamin K2 which have been designated as FOSHU. We evaluated the biologicaleffects of excess intake of a new product, vitamin K2(menaquinone−4:MK−4)containingcalcium tablets, for 4 weeks.Twenty healthy male and female volunteers, aged 20 to 69, took 5 times as much as recommendedamount calcium tablets with 7.5 mg of vitamin K2(30 tablets, 7.5 g). γ−Carboxylatedosteocalcin(GlaOC)was increased and undercarboxylated osteocalcin(ucOC)wasdecreased after 4 weeks administration. These results suggested that vitamin K2(MK−4)promotes bone formation. Furthermore, there were no adverse events or clinical changes insafety parameters relevant to the product during 4 weeks of period. This study proves thesafety of excess intake of a new product, vitamin K2(MK−4)−containing calcium tablets.(Jpn Pharmacol Ther 2008;36:1189−95)KEY WORDS Vitamin K2,Calcium,Osteocalcin,Bone formation,Excess intake