Background

The differences in conditions of enteric-coated acid-labile drug release and absorption between healthy subjects in bioequivalence studies and gastrointestinal patients in clinical practice can lead to significant differences in gastric stability of original PPIs and generics. Thus, pathologic duodenogastric reflux (PDGR) and the pH increasing within PPIs administration still remain unaccounted for.

Methods

Two-stage modified comparative dissolution testing of original omeprazole (OO) and four generics (G1;2;

;4) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±0.05) to pH 7.0 (7.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH 7 exposure time of resistance to PDGR for omeprazole is 4 minutes, i.. the active substance should not be released within 4 minutes at pH 7. The exposure at the second stage was conducted with pH 4 (4.0±0.05), that imitated gastric pH after PPI administration. And then we also moved drugs to pH 7 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH 7 solution at the first stage were different for OO and generics. For OO, these values were 4,7±0,7%; 41,4±

,0%; 62,±4,0%; 79,±2,%; ,±2,%; ,6±2,%; 80,6±4,4%; for Generic1 - 0; 49,±,%; 88, ±2,%; ,4±,7%; 88, 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,%; 66,7±,2%; 76,4±7,4%; ,±,%; 86,0±,7%; ,6±,%: for Generic - 80,±,6%; ,±1,%; , ±,2%; ,±2,7%; ,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,±1,7%; ,4±0,%; ,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,±1,1%, respectively.

An analysis of the omeprazole concentration in pH 7 solution at the second stage revealed the following parameters after the same time: for OO - 4,4±0,6%; 40,

±,0%; 62,±2,0%; 80,0±,1%; 85,4±2,%; ,±,4%; 80,±,%; for Generic1 - 0; 67,0±7,%; 89,7±2,%; 91, ±4,%; 89,1±1,6%; 88,±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±,6%; 75,1±7,%; ,0±6,0%; 88,4±,2%; 88, 6±1,%; 87,±1,0%; for Generic4 - 85,±0,%; 85,6±0,%; ,7±0,%; ,7±,0%; ,4±0,%; ,4±0,%; ,±0,4%, respectively. Generic release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic

and Generic4 makes PDGR and inhibited gastric acid secretion due to PPIs administration the potential causes of decreased enteric-coated acid-labile drugs stability.

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ラットに

3H

-CU-

83

(S)を25μg/kgで静脈内あるいは経口投与し，血液中濃度および尿糞中排泄を検討した．
静脈内投与後の血液中濃度推移は投与後

5

分より上昇し，投与後45分に25.74ng eq./mlのC_maxを示し，それ以後t_1/2

3

.05時間とt_1/2 33.09時間の二相で減少した．投与後72時間までのAUCは135.42ng eq.·hr/mlであった．
経口投与では，投与後

3

時間でC_max 4.10ng eq./mlに達し，以後t_1/2α 4.46時間とt_1/2β 26.

83

時間の二相で減少した．投与後72時間までのAUCは48.62ng eq.·hr/mlであった．
静脈内投与と経口投与のいずれの場合も，尿および糞中への放射能の排泄は，投与後48時間でほぼ終了した．静脈内投与では，投与後72時間までに投与量の30.52%が尿中に，60.42%が糞中に排泄された．経口投与では，同じく72時間までに40.34%が尿中に，69.24%が糞中に排泄された．

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The possibility of attenuation of microseismic waves due to the presence of an upward folding of the ocean bottom into the liquid is discussed in this paper. The upward folding of the ocean bottom has been idealized by means of an irregularity in the form of a rectangle intruding into the liquid and the evaluation of the displacement component at any point of the solid medium has been carried out in two stages. First, the change in the incident mode of the surface wave due to the presence of the rectangular irregularity has been determined, and second, the subsequent change of the resulting displacement components due to the termination of the liquid layer and the step change in elevation of the solid medium at the continental margin has been discovered. Finally, numerical calculation has been made to determine the attenuation of the microseismic waves of different periods due to the presence of the rectangular irregularity at the ocean bottom.

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BCR-ABL1 International Scale（IS）測定はチロシンキナーゼ阻害剤で治療されている慢性骨髄性白血病（CML）患者の治療効果をモニターする上で重要な検査法である。稀ではあるが，BCR-ABL1 IS測定ができないCMLが存在することが知られている。本研究において，我々は，そのようなBCR-ABL1 IS測定のできないCML患者を経験し，分子生物学的な方法で，その原因を解明した。本例ではABL1遺伝子における切断点がa2エクソン内にあることが分かり，そのことがABL1のa2エクソンを欠いた

14a（a）キメラ遺伝子のmRNAのみの発現を誘導していた。a2エクソンは本邦における検査部でのIS測定において重要な要素であり，これが欠損することが測定不能の原因であった。このようなIS測定ができない稀なCML症例をさらに集積して，その分子構造を解明することが待たれる。

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The aim of the present study was to evaluate the predation efficacy of Bdellovibrio bacteriovorus on multidrug-resistant (MDR) or extensive drug resistant (XDR) gram-negative pathogens and their corresponding biofilms. In this study, we examined the ability of

. bacteriovorus to prey on MDR and XDR gram-negative clinical bacteria, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Results showed that

B

. bacteriovorus was able to prey on all planktonic cultures, among which the most efficient predation was observed for drug-resistant

E

. coli, with a .11 log10 reduction in viability. Furthermore,

B

. bacteriovorus demonstrated promising efficacy in preventing biofilm formation and dispersing the established biofilm. Reductions in biofilm formation of

E

. coli, K. pneumoniae, P. aeruginosa, and A. baumannii co-cultured with

B

. bacteriovorus were 65.2%, 37.1%, 44.7%, and 36.%, respectively. Meanwhile, the established biofilms of

E

. coli, K. pneumoniae, P. aeruginosa, and A. baumannii were significantly reduced by .4%, .%, .1%, and 79.%, respectively. A visual analysis supported by scanning electron microscopy demonstrated the role of

B

. bacteriovorus in removing the established biofilms. This study highlights the potential use of

B

. bacteriovorus as a biological control agent with the capability to prey on MDR/XDR gram-negative pathogens and eradicate biofilms.

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The acetone extracts from three samples of the hepatopancreas of the poisonous scallops obtained on the Okhotsk Coast of Hokkaido Island were fractionated into two parts, hexane soluble fraction (fraction H) and 85% aqueous ethanol soluble fraction (fraction ) by partition to two layers. The majortoxic components in the mouse assay of “diarrheic shellfish toxin” by intra-peritoneal injection were found to be free unsaturated fatty acids showed the following toxicity in MU per g, 18:1 n- 35, 18:2 n-6 , 18: n- 167, 18:4 n- , 20: n- 167, and :6 n- , respectively. Toxicity of the fraction Hin MUper g was much lower than that of the fraction . However, the toxicity of the fraction H per 1 g of the hepatopancreas was about twice that of the fraction , since the fraction Hwas much more abundant than the fraction in the hepatopancreas. The method for the assay of the diarrhetic shellfish toxin must be reexamined by considering the toxic effect of the free unsaturated fatty acids.

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L'entree en Iran des armees britannique et sovietique s'est produite en aout 1941. Elle ebranla du coup le regime de la dynastie pahlavi qui etait au pouvoir depuis 16 ans, et mena le pays vers l'instabilite politique et le chaos social. La defaite de l'arme gouvernementale, qui etait le pivot du regime de Reza Shah, reduisit considerablement le controle du gouvernement central dans le pays. Cette situation politico-sociale confuse permit le developpement de differents mouvements politiques en Iran. C'est ainsi que le 16 aout 1942 le parti clandestin Komeley Jiyanewey Kurdistan (J-K) est ne a Mehabad, une ville au nord-ouest de l' Iran. Des sa formation, ce parti a su etendre sa sphere d'activite et, en une courte periode de temps, a fini par mettre sous son influence la ville et ses alentours. A la fin de la Seconde Guerre mondiale, en ete 1945, le J-K etait devenu une organisation representant le mouvement nationaliste kurde en Iran. C'est a ce moment-la qu'un autre parti politique, le Hizbi Dimokratiki Kurdistan (HDK), fonde par Qazi Mihemed a Mehabad aussi, devait remplacer le J-K. Des le janvier 1946, le HDK proclama l'instauration de la≪Republique de Kurdistan≫. Cependant, les troupes sovietiques qui avaient pris sous leur protection la Republique evacuerent les terres iraniennes, en mai 1946. Six mois plus tard, sous la pression militaire du gouvernement central iranien, la republique s'ecroula. Deux theories tentent d'expliquer le passage du J-K au HDK. William Eagleton Jr., par exemple, affirme dans The Kurdish Republic of 1946 que le HDK a ete cree sur le conseil des autorites sovietiques. L'ex-secretaire general du Parti Democratique du Kurdistan d'Iran, 'Ebd el-Rehman Qasimlu maintient par contre que Qazi Mihemed a etabli le nouveau parti de sa propre initiative, eu regard a la situation politique de cette epoque-la. Il considere que la passage du J-K au HDK comme etant l'evolution d'un parti nationaliste clandestin en un parti democratique. En analysant ces deux theories et en se basant sur les autobiographies des personages qui se sont engages dans cet evenement, cette etude tentera d'examiner le principe directeur et les activites du J-K et de mieux comprendre les raisons pour lesquelles le J-K devait etre remplace par le HDK. La conclusion generale portera sur les differents objectifs politiques du J-K et du HDK. Le J-K visait l'elevation du niveau culturel du peuple tout en luttant contre le tribalisme, qui etait, selon lui, le probleme majeur de≪la nation kurde≫, et cela en ecartant toute idee de revolte militaire. Le J-K a aussi exclu de son cadre les elites sociales telles que les leaders des tribus et dirigeants religieux de peur qu'ils n'excercent une influence sur les membres du parti. L'automne de 1944 fut le debut d'une nouvelle ere pour le mouvement kurde. Alors que l'espoir de l'autodetermination augmentait parmi le peuple a mesure que s'approchait la fin de la guerre, la necessite de la force militaire a commence a se faire sentir dans le J-K. C'est pour cela que s'est produite au sein du parti une tendance a compter sur l'aide militaire des sovietiques et a recourir au leadership de Qazi Mihemed, qui avait une certaine influence meme sur les leaders tribaux. Mais cette tendance etait essentiellement incompatible avec la ligne fondamentale du J-K et, graduellement, a prive ce parti de sa raison d'etre. Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier d'abord les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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Nアルキル,4:,10-ペリレンテトラカルボン酸モノアンヒドリド=モノイミド[4a～]と芳香族アミン(アニリン,p-トルイジン,p-アニシジン,,-キシリジン,4-アミノナゾベンゼン,およびo-フェニレンジアミン)を縮合して非対称型,4:,10-ペリレンビス(ジカルボキシミド)誘導体-N-アルキル-N'-アリール-,4:,10-ペリレンビス(ジカルボキシミド)(〔a～〕,〔6a～〕,〔7a～〕,〔a～〕,〔a～〕,および〔10a～〕)を合成した. これらの各誘導体はすべて赤色系の色相を示し, 顔料試験の結果N-ブチル-N'-アリール-,4:,10-ペリレンビス(ジカルボキシミド)(たとえば〔〕や〔6〕)がとくにすぐれた耐光性を示した.

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【目的】ラテックス法試薬（LZテスト‘栄研’H.ピロリ抗体：栄研L，LタイプワコーH.ピロリ抗体・J：和光L）の診断精度を検討する。

【方法】検診受診者899名の血清を用い，標準である

プレート‘栄研’H.ピロリ抗体II（カットオフ U/ml：-plate）を対照に比較解析した。

【結果】内視鏡的Helicobacter pylori感染診断に基づく

-plateの感度・特異度・偽陰性率は.7%・.0%・15.%であった。栄研Lの感度は68.%と-plateに比べ有意に低く，特異度は98.2%と同等，偽陰性率は31.%と有意に高かった。和光Lの感度は.%と同等，特異度は92.6%と有意に低く，偽陰性率は16.2%で同等であった。胃がんリスク層別化検査の偽A群率は，-plateの13.%に比べ，栄研Lは27.%と有意に高く，和光Lは14.4%と同等であった。

【結論】

-plateに比べ栄研Lの感度は有意に低く，偽陰性率・偽A群率は有意に高かった。和光Lは感度・偽陰性率・偽A群率のいずれも-plateと同等であった。

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2014年LIA法を原理とする血清H. pylori抗体価測定キット「LZテスト」が上市された。LZテストは従来のELISA法によるプレートとは異なる測定系であり, プレートに関する知見が通用する保証はない。今回, LZテストの陰性高値(抗体価.0～.U/ml)がプレートと同様の取扱いができるかを検証した。対象は両検査法で抗体価を同時測定し両抗体価の少なくとも一方が10U/ml未満であった230例であり, 陰性高値内のH. pylori感染状態の構成比および“新ABC分類”(カットオフ値＝.0U/ml)による分類結果を比較した。プレートでは陰性高値となる未感染は存在せず, LZテストでは16例(.%)であった。未感染98例に新ABC分類を適応するとプレートではA群例(99.0%)D群1例(1.0%), LZテストではA群例(.7%), BCD群合わせて15例(15.%)であった。LZテストの陰性高値には未感染が多く含まれ, 新ABC分類をLZテストで行うと未感染者を要精検とする割合が増えるため, 未感染者が多数を占める検診ではプレートを用いることが望ましい。

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-1. Sixteen phosphate buffered saline (PBS), boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-7,-diene-,,6β-triol (1). 1 induced ALP activities of MCT-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MCT-1 cells by 1, ergosterol (2), ergocalciferol (), cholesta-,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , and 6 did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C- and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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The compound, ()-1-(1,-benzodioxol--yl)--(4-chlorophenyl)prop-2-en-1-one (I), , crystallizes in the monoclinic crystal system with space group P2₁/c and cell constants: a = .7231(15), = 4.9239(4), c = 11.9995(7)Å, β = 99.953(6)°, V = 1322.37(16), Z = 4. ()-1-(1,-Benzodioxol--yl)--(,4-dimethoxyphenyl)prop-2-en-1-one (II), , crystallizes in the triclinic crystal system, space group P1 with a = .2961(2), = 13.8829(6), c = 14.6713(7)Å, α = 64.185(4), β = .560(). γ = .966()°, V = 1510.10(10), Z = 4. Hydrogen bonding and crystal packing effects influence the twist angle between the mean planes of the 1,-benzodioxol--yl and benzene groups in both I and II, while π-π stacking interactions help to stabilize the crystal packing.

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Clinical efficacy and safety, and also the optimal dose of cefuroxime axetil (CXM-AX) in the treatment of infections in the Dentistry and Oral Surgery were evaluated. To the patients with periodontitis (Group I), pericoronitis (Group II) and osteitis of the jaw (Group III), CXM-AX was orally administered in three divided doses after meals, with the daily dose of either 750mg or 1500mg.
1. In 234 cases in which clinical efficacy was assessable, the efficacy rates (rate of ‘Excellent’ or ‘Good’) by physician's assessment and by assessment based on numerical rating on Day were comparable, i.. 80. % and . %, respectively. When these rates were evaluated for each disease group, the efficacy rate by the physician's assessment was the highest in Group I (86.%), whereas there was almost no difference in efficacy rates by assessment based on numerical rating on Day among three disease groups (.7%-.%) . In the clinical efficacy assessment based on numerical rating on Day for each dose level, the efficacy rate in the 1500mg group (92.7%) was higher than that in the 750mg group (.%), but no significant difference was observed between the two dose level groups.
2. Bacteriological response was assessable in 96 cases. The clinical efficacy rates in these assessable cases were .4% by physician's assessment, and .% by assessment based on numerical rating on Day . In both assessments, the clinical efficacy rate was higher in monomicrobial infection cases than in polymicrobial infection cases, but there was no significant difference. In the assessment of bacteriological response by the Committee, bacterial elimination was observed in 72.%.
. A total of 156 strains of organisms were isolated from 96 patients subjected to bacteriological evaluation. (Streptococci: 87, Peptostreptococci : 27, Bacteroides : 14, Staphylococci : ,

B

. catarrhalis and others : 20) The of cefuroxime for all the isolates was 0.39μg/ml.
4. Adverse events were observed in 11 (4.6%) out of 239 cases ; gastrointestinal tract disorders in 10 and candidiasis of tongue in 1. Among these 11 cases, 6 cases did not require withdrawal of the test drug. As to the remaining cases, adverse events disappeared within days from onset after withdrawal of the test drug.
. Abnormal changes in laboratory test values were noted in 10 cases (6.2%, a total of 13 values) out of 161 cases examined. They were elevation of S-GPT (6) and S-GOT (), increase in eosionophil (2), and elevation of BUN (1), and Al-P (1) .
6. Assessment of usefulness was made based on efficacy and safety. Usefulness was assessed as ‘Satisfactory’ or above in 184 cases (78.%) out of 235. The usefulness rate was the highest in Group I (.7%), but there was no significant difference among the three disease groups.
From the above results, CXM-AX was considerd to be useful in the treatment of infections in the Dentistry and Oral Surgery. As for the standard dose, a daily dose of 750mg proved to exert the expected effects.

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1. The chromosome numbers of 64 species have been studied on which 56 are investigated for the first time.
2. Morphological, anatomical and cytological findings on the Musaceae in the broad sense are considered from a phylogenetical standpoint and three distinct groups:
a) Musa-Ensete, ) Ravenala-Strelitzia-Phenakospermum and c) Holiconia are recognised as suggested by some authors. For these groups sub-familial status is proposed.
. Lowiaceae have been studied for the first time cytologically and their chromosome morphology, distinct from that of any other group of Zingiberales, confirms their claim to familial status.
4. Consideration of the conflicting theories proposed to account for the higher chromosome number in genera like Globba, Alpinia, and Phaemeria, etc. leads to rejection of Chakravorti's hypothesis of wholesale fragmentation of chromosomes and the acceptance of the opposed view of Raghavan and Venkatasubban and others.
. Holttum's transference of the genus Zingiber to the tribe Hedychieae has been given cytological support on the following points:
a) the basic number in the genus Zingiber correlates with that of Kaempferia.
) the new tribe Alpinieae (which is infact Zingibereae without Zingiber) have consistently 48 chromosomes in their somatic complements.
6. It is suggested that the African representatives of Kaempferia should be given the status of genus; Cienkowskya on the following points:
a) the difference in floral morphology
) geographical separateness and
c) the difference in the number and morphology of the chromosomes. By comparing the present and past findings, various lines of evolution of the chromosome complements within each group are discussed.
7. The basic number 11 is considered to be probably the original one for the Zingiberales as a whole, being present in Ravenala which is the most primitive member in the order. From this secondary basic numbers have arisen through evolution.

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