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;

;) 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 minutes, i.. the active substance should not be released within minutes at pH 7. The exposure at the second stage was conducted with pH (.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

, 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 ,7±0,7%; 41,±,0%; 62,±,0%; 79,±2,%; ,±2,%; 81,±2,%; 80,±,%; for Generic1 - 0; 49,±,%; , ±2,%; 90,±,7%; , 2±2,2%; 87,±2,0%; ,±1,1%; for Generic2 - 0; 30,±,%; 66,7±,2%; 76,±7,%; ,±,%; 86,0±,7%; 84,±,%: for Generic - 80,±,%; ,±1,%; , ±,2%; ,±2,7%; 81,±2,1%; ,1±2,0%; ,0±2,%; for Generic - ,±1,7%; 84,±0,%; 84,2±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 -

,±0,%; 40, ±,0%; 62,±2,0%; 80,0±,1%; ,±2,%; ,±,%; 80,±,%; for Generic1 - 0; 67,0±7,%; 89,7±2,%; 91, ±,%; 89,1±1,%; ,±1,%; 87,±1,2%; for Generic2 - 0; 42,2±,%; 75,1±7,%; 81,0±,0%; ,±,2%; , ±1,%; 87,±1,0%; for Generic - ,±0,%; ,±0,%; 84,7±0,%; ,7±,0%; 84,±0,%; 84,±0,%; 84,±0,%, respectively. Generic release and degradation were completely realized at pH .

Conclusion

Decreased gastric stability of Generic

and Generic 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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Six full-length cDNAs encoding pig cytochrome P450 (CYP) enzymes, CYP1A1, CYP2A19, CYP2, CYP2C33v, CYP2C49, and CYP21, were isolated and sequenced. The cDNA sequences of pig CYP1A1, CYP2A19, CYP2, CYP2C49, and CYP21 showed high similarity to human CYP1A1 (.%), CYP2A13 (.%), (81.1%), CYP2C18 (.%), and (.%), respectively, and pig cDNA showed high similarity to rat CYP2C23 (79.2%). Reverse transcription-polymerase chain reaction (RT-PCR) assays revealed hepatic gene expression of all these pig CYP enzymes: the order of expression was and > CYP2C49 > CYP1A1 and CYP2A19 > . In the kidney, the gene was expressed at the same level as in the liver, but the CYP1A1, CYP2A19, and genes were expressed at lower levels than in the liver. Little renal gene expression of CYP2C49 and CYP21 was observed. We revealed for the first time the full-length cDNA sequences encoding pig CYP1A1 and five CYP enzymes belonging to the CYP2 gene family, thus making it possible to examine the gene expression levels of these CYP enzymes in pig tissues by RT-PCR.

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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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ドコサヘキサエン酸エチル (-DHA) の大量精製方法の確立を目的とし, 固定化Rhizomucor mieheiリパーゼでマグロ油由来のエチルエステル (-DHA 55; -DHA含量, 55mol%) をラウリルアルコール (LauOH) でアルコリシスした。固定化リパーゼを充填したカラム (.0g; ×63mm) に-DHA/LauOH (1 : 7, mol/mol) の混液を30℃, 10mL/hの流速で負荷した。その結果, エステル交換率は58%に達し, エチルエステル画分の-DHA含量は87mol%まで上昇した。この固定化酵素リアクターを150日間連続運転すると, エステル交換率は48%まで低下したものの, -DHA含量はほとんど低下せずmol%まで上昇していた。カラムから溶出した反応液中のエチルエステルは薄膜蒸留により収率よく回収できたが (%), この画分には2.wt%のLauOHと.wt%のラウリルエステルが混在していた。このうち, ラウリルエステルは尿素包括により完全除去することができた。一連の精製操作により, -DHA55に含まれていた-DHAの52%が回収でき, -DHA含量をwt%まで高めることができた。

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The performance of single pitch and multi pitch screw anchors during the application of installation torque is presented. An experimental testing program was conducted using five models of screw anchors with different geometry. The effect of the shape of the screw element, sand properties, and installation depth on the required installation torque value was examined. A theoretical model was developed from which the required installation torque value can be calculated in terms of the influencing factors. The required installation torque can be determined in terms of the ultimate uplift resistance calculated from any of the available theories. Based on the actual installation torque value measured in the field, the anticipated pullout capacity can be back calculated from the present theory. A comparison between theoretical and experimental results showed good agreement. Also, good agreement was observed when the present theoretical results were compared with the available field results reported in the literature.

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It has been shown after mathematical and mechanical investigation that Limit Equilibrium Method (LEM) can be considered as a method to obtain the necessary condition of Slip Line Method (SLM), and that the solution can be obtained under the condition that F_s=1 and ∂F_s/∂θ=O, where F_s is the safety factor and θ is the inclination of the plane on which the safety factor is defined. Next, the generalized LEM (GLEM) is proposed, dealing with the following points : (1) Triangular or quadrangular blocks can be treated; (2) Safety factors are defined also on interblock planes; and () All types of plastic problems, slope stability, bearing capacity, and earth pressure are identically formulated. Two situations regarding treatment of the moment equilibrium condition are discussed. GLEM is applied to well-known problems. The results agree well with those obtained by theoretical methods. GLEM can be used to obtain the distribution of earth pressure or bearing capacity. GLEM, Iike ordinary LEM, is very effective for the practical problems, but GLEM is more theoretical and it can result in more accurate solutions.

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The effects of T- (2-[2-(1-benzylpiperidin--yl)ethyl]-2,-dihydro--methoxy-1H-pyrrolo[,-]quinolin-1-one hemifumarate), a new quinoline derivative, on acetylcholinesterase (AChE) activity and acetylcholine (ACh) release were compared with those of the well-known cholinesterase inhibitors tacrine and 2020. T-, tacrine and 2020 all concentration-dependently inhibited AChE in rat brain homogenate (IC_50s = 109., 84.2 and 11. nM, respectively). In addition, although tacrine strongly inhibited butyrylcholinesterase (BuChE), T- and 2020 showed only weak activity on BuChE in human plasma. In ex vivo experiments, intraperitoneal administration of T- at a dose of 30 mg/kg inhibited AChE activity in the hippocampus, frontal cortex and parietal cortex of rats. The effect of T- on the extracellular ACh concentration in rat brain was measured using in vivo microdialysis. T- at doses of 10 and 30 mg/kg, i.p. increased the extracellular ACh concentration in the hippocampus and striatum in a dose-dependent manner. These findings suggest that T- activates the central cholinergic system by selectively inhibiting AChE activity, while weakly affecting peripheral BuChE activity, and that T- increases the extracellular ACh concentration in the brain, which is followed by inhibited AChE activity.

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The association between apolipoprotein (Apo-) polymorphism and the response of plasma cholesterol to dietary therapy (cholesterol intake of less than 300mg/day) was investigated for about weeks in 208 nonfamilial hypercholesterolemia patients (/ 161, / 47). The baseline lipoprotein concentration and the intake of energy and lipids were not significantly different between subjects with / and those with / phenotypes. After the dietary therapy plasma total cholesterol and low density lipoprotein cholesterol were significantly decreased in both phenotype groups (p<0.05). The patients with / had significantly smaller reductions of LDL-C than the patients with /. The changes of LDL-C showed a significant difference between the patients with / and / by the Kruskal Wallis test (p=0.041). The presence of / predicted the degree of cholesterol reduction following dietary therapy.

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The relationship between withers height and hip height of 378 purebred Holstein-Friesian cows in Japan aged over , which have good dairy conformation and heigh milk production, is investigated by the Writer from biometric standpoint. And the results are as follows:
1. Biometric constants.
Withers height. (c.m.) Hip height. (c.m.)
M……135.93±0, 167 137.33±0.184
σ…….±0.118 .29±0.130
V…….55±0.087 .±0.095
Q…….17±0.228 .45±0.250
Mi……135.40±0.210 136.90±0.230
Mo……137.00±0.205 139.00±0.225
S……-0.±0.042 -0.32±0.042
2. The frequency curve of withers height is Y=378/.√2π -1/2(χ-135.93/.)2×2, and that of hip height Y=378/.29√2π -1/2(χ-137.33/.20)×2.
.The correlation coefficient between there two characters is +0.96±0.003.
.The regression equations are (denoting withers height and hip height by X and Y, respectively).
X=0.Y+16.45……(1)
Y=1.05X-.40……(2)

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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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In Japan, aseptic meningitis cases due to enterovirus infections increase every summer in various degrees with an incidence peak usually in July. During the past 11 years from 1981 through 1991, a total of , 595 enterovirus isolations from aseptic meningitis cases were reported from 54 participating laboratories. Eight enterovirus types caused large epidemics; more than 100 isolations of each type from aseptic meningitis cases were reported for every epidemic year of the respective type. They were coxsackievirus (C) types and , echovirus () types , , 7, , 18 and 30. Among these, the highest meningitisassociating frequency was reported for 30, representing .% of the total isolations reported for the type during this period, followed by , 71.1%. The frequencies of , 7, and CB were in a range from 54.% to 44.%, while that of 18 was 37.7% and that of CB 21.0%. During the epidemics, enterovirusassociated meningitis was most frequently reported among children of -7 years of age. High frequencies were also shown in infants less than 1-year of age in some types. A total of , 240 enteroviruses were isolated from cerebrospinal fluid of aseptic meningitis cases, representing 49.% of the cases with enterovirus isolation.

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A biosynthetic pathway for (

)-methyl cinnamate formation was evaluated in Tricholoma matsutake by tracer experiments using ¹³C- and ²H-labeled precursors. One hundred percent selective ¹³C incorporation was observed when L-[1,2,,,,,7,,-

13C₉

, ^15/N]phenylalanine was converted to (

E

)-[1,2,

3

,

4

,

5

,

6

,7,

8

,

9

-

13C₉

]cinnamate and (

E

)-[1,2,

3

,

4

,

5

,

6

,7,

8

,

9

-

13C₉

]methyl cinnamate. Similarly, 100% selective ¹³C incorporation was observed when (

E

)-[1,2,

3

,

4

,

5

,

6

,7,

8

,

9

-

13C₉

]cinnamate was converted to (

E

)-[1,2,

3

,

4

,

5

,

6

,7,

8

,

9

-

13C₉

]methyl cinnamate. In contrast, the ²H incorporation selectivities were

82

.1% and 81.

4

% when L-[2,

3

,

4

,

5

,

6

,7,7,

8

-

2H₈

]phenylalanine was converted to (

E

)-[2,

3

,

4

,

5

,

6

,7,

8

-²H₇]cinnamate and (

E

)-[2,

3

,

4

,

5

,

6

,7,

8

-²H₇]methyl cinnamate, respectively. Thus, T. matsutake synthesizes (

E

)-methyl cinnamate from L-phenylalanine via (

E

)-cinnamate. (

E

)-cinnamate was likely formed through two pathways: one was major and the other was a minor.

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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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