Effects of Choto-san (Diao-Teng-San) on microcirculation of bulbar conjunctiva and hemorheological factors in patients with asymptomatic cerebral infarction

In this study, the effects of Choto-san ( 釣藤散 ) on the microcirculation of bulbar conjunctiva in 16 patients with asymptornatic cerebral infarction were investigated with a video-microscopic system. After the administration of Choto-san for four weeks, variables of microcirculatory flow of the bulbar conjunctiva, that is, the internal diameter of vessels, flow velocity and flow volume rate were increased (p<0.05) . Erythrocyte aggregability, evaluated by measuring the maximum diameter of a column of intravascular erythrocyte aggregation, was also improved (p<0.05) . Simultaneously, hemorheological factors such as whole blood viscosity, plasrna viscosity, erythrocyte deformability and leukocyte deformability were examined. Choto-san improved deformability of both erythrocytes and leukocytes (p<0.05) , but not blood viscosity. These results suggest that Choto-san may have favorable effects on cerebrovascular disorders through changes in microcirculatory flow, erythrocyte aggregability and blood cell deformability. 今回,無症候性脳梗塞患者16名を対象に,眼球結膜微小循環に及ぼす釣藤散の効果をビデオ顕徴鏡システムを用いて検討した。釣藤散を4週間投与後,眼球結膜微小循環の血管内径,血流速度,血流量が増加した(p<0.05)。血管内赤血球集合現象を認める血管の最大内径で評価ざれる赤血球集合能も改善した(p<0.05)。同時に,血液レオロジー因子である全血粘度,血漿粘度,赤血球変形能,白血球変形能も検討したところ,釣藤散は赤血球と白血球の変形能を改善したが(p<0.05),血液粘度は改善しなかった。以上の結果から,釣藤散は徴小循環血流や赤血球集合能,血球変形能を改善することで,脳血管障害に好影響を与える可能性が示唆された

Pharmacokinetic study of Paeoniflorin Paeonimetabolin-I and Glycyrrhetic acid in humans after oral administration of Paeony Root, Glycyrrhiza and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang)

The pharmacokinetics of Paeoniflorin (PF) , Paeonimetabolin-I (PM-I) and Glycyrrhetic acid (GA) after oral administration of the decoction of Paeony Root (PR) and Glycyrrhiza (GR) and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang ; SK) were studied using human subjects. Concerning the intra- and inter-individual variability of PF and PM-I after oral administration of SK, each inter-individual coefficient of variation (CV) of the pharmacokinetic parameters was larger than its intra-individual CV. There was no significant correlation between each pharmacokinetic parameter and each subject\u27s physiques. These results suggested that a large inter-individual variability were not caused by differences in the subjects\u27 physiques. Regarding a comparison of the pharmacokinetic parameters, AUC and Cmax of PF of PR were significantly higher than those of SK, and MRT and Tmax of PM-I of SK were significantly longer than those of PR. AUC of GA of SK was significantly higher than those of GR. There is the possibility that PR would be better than SK when a stronger efficacy of PR is expected in a short time, and SK would be beter than PR when a longer efficacy of PR or a stronger efficacy of GR is expected. ヒト健常人において芍薬・甘草・芍薬甘草湯経口投与時のペオニフロリン(PF),ペオニメタボリン-I(PM-I),グリチルレチン酸(GA)の葉物動態の研究を施行した。芍薬甘草湯投与後のPF,PMIの個体内・個体間変動については,各々の個体問変動係数が個体内変動係数よりも大きく,また,全ての薬物動態の各パラメータと被験者の体格との間には相関はみられなかった。芍薬・甘草と芍薬甘草湯との比較では,芍薬のPFのAUC,Cmaxが芍薬甘草湯のものに比較して有意に高値を示し,芍薬甘草湯のPM-IのMRT,Tmaxが芍薬に比較して有意に長かった。また,芍薬甘草湯のGAのAUCは甘革単独投与のものに比較して有意に高値を示した。このことから,短時間に芍薬のより強い効果を期待する際には芍薬単独で用い,芍薬成分のより長い効果や甘草成分のより強い効果を期待する際には芍薬甘草湯として投与する方がよい可能性がある

Endothelium-dependent vasodilator effect of tannin extract from Cinnamonomi Cortex on isolated rat aorta

Cinnamonomi Cortex (the bark of Cinnamomum cassia BLUME) is a crude drug that is widely used in spices and medical products. Although improvement of blood flow by this plant component has long been known, there have been no reports concerning the mechanism involved. We studied the vasodilator actions of this drug especially focusing on the role of endothelium in the isolated vascular bed. Tannin from Cinnamonomi Cortex (TCC) relaxed prostaglandin F_-precontracted ring preparations of rat aorta with intact endothelium. TCC did not cause relaxation of specimens without endothelium, and TCC-induced relaxation was inhibited by pretreatment with 10^M N^G-nitro-l-arginine methyl ester. Dimer, trimer, tetramer, and pentamer components of TCC also produced endothelium-dependent vasodilatation. Stronger relaxation was caused by higher molecular weight tannins, and endothelium-dependent vasodilation even appeared at low concentrations. In conclusion, we found that TCC exhibits an endothelium-dependent vasodilatation in the isolated rat aorta mainly via endothelium derived NO. NO mediated endothelium-dependent relaxation seems to be more potent for TCC with higher molecular weight than that with lower molecular weight. 桂皮の血流改善作用については古くから知られており,これに関連した報告はあるものの,その詳細な検討はなされていない。今回我々はマグヌス法を用いて,ラット胸部大動脈輪状標本における桂皮含有クンニンの血管作動性について検討した。桂皮含有タンニンは,プロスタグランディンF_(PGF_)の血管収縮に対し,内皮保存血管において濃度依存性に血管弛緩作用が認められた。しかし,内皮除去血管及ぴN^G-nitro-l-argininemethyl ester(L-NAME)前処置内皮保存血管においては,血管弛緩作用はほぼ消失した。以上より,桂皮含有タンニンの血管弛緩作用は内皮依存性であることが明らかとなった。桂皮含有タンニンをさらに二量体から五量体までのタンニン画分に分取し検討したところ,二量体以上の重合したタンニンにおいて血管弛緩作用が認められた。また,重合度が増すに従い血管弛緩作用はより低い濃度で発揮され,作用も増強されることが明らかとなった

Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis

Optimal liver drainage rate for survival in patients with unresectable malignant hilar biliary obstruction using 3D-image volume analyzer

Background: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. Objectives: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. Design: This study was a single-center retrospective cohort study. Methods: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. Results: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with 80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p Conclusion: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study