薬理と治療
Volume 38, Issue 3, 2010
Volumes & issues:
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シリーズ
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- 「いろいろな臨床試験のケースレポート: 温泉のRCTから看護のSRまで」
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TOPICS
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ORIGINAL ARTICLES
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歯周病原細菌に対するマスティックエッセンシャルオイルの選択的な抗菌作用
38巻3号(2010);View Description Hide DescriptionWe studied the antimicrobial activity of mastic essential oil against oral bacteria of periodontalpathogens and normal bacteria, and compared the antimicrobial activity of masticessential oil to cetylpyridinium chloride and minocycline hydrochloride against oral bacteria.After measuring the minimum inhibitory concentration(MIC)of 6 oral bacterial species,we found that mastic essential oil was effective against Porphyromonas gingivalis and Fusobacteriumnucleatum, which are periodontal pathogens, but wasn’t effective against Streptococcusmitis, Streptococcus salivarius, Lactobacillus casei and Lactobacillus salivarius, which are normalbacterium in the oral cavity. On the other hand, cetylpyridinium chloride and minocyclinehydrochloride were effective against not only P. gingivalis and F. nucleatum but also S. mitis,S. salivarius, L. casei and L. salivarius.These results indicated that mastic essential oil showed selective antibacterial actionagainst periodontal pathogens(P. gingivalis and F. nucleatum)compared to normal bacteria.Further, these selective antibacterial actions of mastic essential oil have higher potential thanthat of cetylpyridinium chloride and minocycline hydrochloride.(Jpn Pharmacol Ther 2010;38:257−60)KEY WORDS Mastic, Antimicrobial activity, Periodontal pathogens, Porphyromonas gingivalis,Fusobacterium nucleatum -
糖尿病ラットへのグルコース負荷試験におけるD−プシコースの血糖低下作用
38巻3号(2010);View Description Hide DescriptionGlucokinase play a key role in the regulation of glucose homeostasis in mammals.Hepatic glucose metabolism is increased by the translocation of glucokinase from the nucleusto the cytoplasm in the liver. We investigated the effects of D−psicose, a rare sugar, on thetranslocation of glucokinase from the nucleus to the cytoplasm in the liver of Goto−Kakizakirats, an animal model of type 2 diabetes, and Wistar rats as controls. D−Psicose induced translocationof glucokinase from the nucleus to the cytoplasm in the liver of both strains of rats.D−Psicose suppressed the increase of plasma glucose levels after glucose loading in Goto−Kakizaki rats. These results suggested that D−psicose can prevent postpandial hyperglycemiaby improving the translocation of glucokinase from nucleus to cytoplasm in the liver of diabeticrats. D−Psicose is expected to have a beneficial effect in the control of blood glucose levelsin type 2 diabetes.(Jpn Pharmacol Ther 2010;38:261−9)KEY WORDS Glucokinase, D−Psicose, Diabetes, Liver, Rat -
神経因性疼痛に対する新規磁気刺激装置Angel Touch の作用機構
38巻3号(2010);View Description Hide DescriptionAlthough magnetic stimulation(MS)has a potential effect to prevent various CNS diseasesincluding depression and sustained pain, the certain mechanisms are not fullyunderstood. Recent studies demonstrated that the MS can induce Ca2+ influx into neuronand glia in cultured cells lead to increased intracellular phosphorylation. In addition, we havedemonstrated that MS mimics rat neuropathic pain associated with prevention of neuronaldegeneration. In the present study, we thus, aimed to elucidate the action of MS in relation tothe modulation of spinal neuro−glia interaction and descending inhibitory system.In order to provide rat chronic pain models, male SD rats were subjected to sciatic nerveligation with a 4−0 silk thread. For intrathecal drug injection PE−10 catheter was implantedinto cistern magna. The MS is battery based low power apparatus and is characterized by twodifferent modes of frequencies, 2 KHz and 83 MHz. The two experimental series were carriedout as 1)CCI treatment and 2)descending systems. Rats were given MS for 10 min.from day 7 to day 14 after CCI. The probe of MS was close to the skin where is located in sciaticnerve ligation. The paw withdrawal latency(PWL, sec)evoked by thermal stimuli wasmeasured from day 3 after CCI. After removal of spinal tissue fixed with formalin perfusion,the imunohistochemistry for microglial(Iba−1)or astrocytic(GFAP)activation was performedfollowed by microscopical analysis. In addition, the spinal microdialysis was performed to seethe effect of MS on supra−spinal 5−HTergic systems. We measured 5−HIAA as reflection of5−HT release by MS stimulation without nerve injury. We employed one−way ANOVA andTurkey for multi−comparison among groups. p<0.05 was considered to be significant.Following CCI the rats showed the decrease in PWL from day 3 lasted over day 14. WithMS treatment, the decrease in PWL was significantly reduced during day 10 to day 14. Thiseffect of MS treatment was antagonized by injecting p38−MAPK inhibitor(SB203580)or JNK−1 inhibitor(SP600125)on day 14. Decrease in GFAP immuno−reactivity after CCI wasreduced by MS. Moreover, MS given to non−CCI rats showed a transient increase in spinal5−HIAA.Although the trans−cranial magnetic stimulation is respected to prevent various types ofCNS diseases by inducing c−fos and neurotrophic factors in animal studies, its detailedmechanism is still not understood. In the present study, we demonstrate that a novel magneticstimulator(Angel Touch_)trans−cutaneously exposed can ameliorate neuropathic painvia mechanisms of the activation of spinal astrocyte related to p38−MAPK and JNK activationsand also descending 5−HTergic inhibitory systems. These results firstly indicated thatMS has potential effects on hyperalgasia via activation of the spinal neuron−glia interactionand descending inhibitory systems.(Jpn Pharmacol Ther 2010;38:273−83)KEY WORDS Neuropathic pain, Magnetic stimulation, Neurotrophic factor, p38−MAPK -
ラット慢性疼痛における脊髄グリア細胞およびp38−MAPK 活性の変調と神経栄養因子型治療
38巻3号(2010);View Description Hide DescriptionMechanism underlying neuropathic pain follows peripheral nerve injury is suggestedthat are, the spinal excessive neurotransmission related to glia activation and dysfunctions ofspinal interneuron and bulbospinal descending inhibitory system. Regarding with dysfunctionof neuronal system, some investigations revealed the lack of neurotrophic factor, brainderivedneurotrophic factor(BDNF)may result in these derangements. Four−methylcatechol(4−MC), inducer of BDNF, can mimic neuropathic pain based on the findings that are inductionof BDNF in cultured neuron and astrocyte. We, thus, aimed to characterize the timedependentchanges of neuro−glia interaction including phosphorylation and then modulationby 4−MC.The Sprague−Dawley rats implanted with intrathecal(it.)catheter, were subjected tochronic constriction injury(CCI). Pain behavior was assessed by the plantar testing thatmeasures reduction in paw withdrawal latency(PWL in sec)for 14 days after CCI. 4−MC(1μg/Kg, ip.)was subsequently administered from day 7th. On the 7th and 14th day, p38−MAPK inhibitor(SB203580)was injected it. and the change in PWL was compared amonggroups. On the 14th day, either anti−BDNF or JNK−1 inhibitor(SP600125)was injected it.whether analgesic effects of 4−MC are reversed. For immunohistochemistry, on 7th and 14thday, the animals were perfused for fixation with 4% buffered formaldehyde and spinal tissuesections were employed avidin−biotin complex method(argyrophyria, Iba−1, and glia fibrillaryacidic protein (GFAP)). We counted positive cells microscopically and compared thoseamong groups.The rats showed decrease in PWL with time after CCI. SB203580 reduced decrease inPWL on 7th day, but did not change on 14th day.4−MC reduced decrease in PWL on 14th day, and this analgesic effect was reversed bySP600125 and anti−BDNF it. Following CCI, we found biphasic changes of GFAP stainingthat are, increased GFAP associated with S100β on 7th day, but decreased those on 14th day.These changes of GFAP were reduced by 4−MC treatment.We firstly demonstrated that, the biphasic mediations of spinal astrocyte associated withphosphorylation that is, responsible for initiation and maintenance of mechanisms underlyingneuropathic pain. In particular, the neuronal degeneration associated with astrocytic depletioncould contribute to the chronic stage. We also demonstrated that 4−MC treatment could ameliorateneuropathic pain by preventing the dysfunction of neuro−astrocyte interaction viainducing BDNF.(Jpn Pharmacol Ther 2010;38:285−95)KEY WORDS Neuropathic pain, Spinal neuro−glia interaction, Neurotrophic factor(BDNF), p38−MAPK, 4−Methylcatechol -
胃粘膜防御薬イルソグラジンマレイン酸塩のAspirin 誘起ラット小腸損傷に対する予防効果
38巻3号(2010);View Description Hide DescriptionIrsogladin maleate, a potent mucosal defensive drug, inhibits the development of gastricand intestinal damage in laboratory animals induced by indomethacin, a non−steroidal antiinflammatorydrug. Recently, we succeeded to establish a new method to induce mucosallesions in the small intestine of rats by administration of aspirin into the duodenum. Therefore,it was of interest to examine whether or not irsogladine maleate inhibits aspirininducedintestinal lesions in rats as well as indomethacin−induced intestinal lesions. Male SDrats(9−wk−old)were used. Irsogladine maleate suspended in 2% methylcellulose(MC)was given orally to normally fed rats or to rats deprived of food for 24 hr. One hr later, theabdomen of ether−anesthetized rats was incised and the proximal duodenum was exposed.Aspirin(200 mg/rat)suspended in 2% MC was injected into the duodenum and then the abdomenwas closed. One hr after aspirin treatment, the animals were killed and the stomach andthe small intestine was removed as a unit. Eight samples(1 cm long)were taken out from thesmall intestine in every 3 cm and histologically examined for the damage. The damage wasdivided into 3 degrees and the total of each score of 8 samples is indicated as the lesion indexper rat. Irsogladine maleate(3, 10, 20 mg/kg)tended to inhibit aspirin−induced intestinallesions in fasted rats, yet it significantly inhibited the lesions in normally fed rats. The mechanismof protective action of irsogladine maleate remains unknown.(Jpn Pharmacol Ther 2010;38:297−302)KEY WORDS Irsogladine maleate, Aspirin−induced intestinal lesions, Indomethacininducedintestinal lesions -
脂質異常症におけるロスバスタチン低用量(2.5 mg)からエゼチミブ追加投与あるいはロスバスタチン倍量(5 mg)投与への切り替えの検討
38巻3号(2010);View Description Hide DescriptionThe percentage of change from baseline in low−density lipoprotein cholesterol(LDL−C)after the addition of ezetimibe 10 mg to rosuvastatin 2.5 mg was compared with uptitration torosuvastatin 5 mg. The subjects enrolled in the study were thirty−four out−patients(fourteenmales and twenty females, mean age:64.3 years)with hyperlipidemia who had never beentreated, but after being given rosuvastatin 2.5 mg for six months as initial therapy, had failedto reach the goals of LDL−C levels set by the Japan Atherosclerosis Society Guidelines forPrevention of Atherosclerotic Cardiovascular Diseases 2007 edition(LDL−C levels droppedfrom196.6±27.2 to 129.5±28.0 mg/dL(−34%)). The subjects were randomly assigned intoone of the two groups:rosuvastatin 2.5 mg plus ezetimibe 10 mg or uptitration to rosuvastatin5 mg. After 6 months of treatment, rosuvastatin 2.5 mg plus ezetimibe 10 mg significantlyreduced LDL−C by −31.2% compared with rosuvastatin 5 mg by −17.5%(p<0.01). Also,LDL−C reductions from the baselines showed a significant difference(54.7% versus 46.7%, p<0.05). No specific adverse events were found in either group. In conclusion, these resultsshowed that adding ezetimibe to rosuvastatin 2.5 mg was significantly more effective thanuptitrating to rosuvastatin 2.5 mg at lowering LDL−C.(Jpn Pharmacol Ther 2010;38:305−11)KEY WORDS Rosuvastatin, Increase of statin, Ezetimibe, Combination of ezetimibe
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