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±.05) to pH 7. (7.±.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.±.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±

,7%; 41,4±,%; 62,8±4,%; 79,5±2,9%; ,5±2,9%; ,6±2,9%; 80,6±4,4%; for Generic1 - ; 49,±9,9%; 88,8 ±2,8%; 90,4±,7%; 88, 2±2,2%; 87,±2,%; 85,9±1,1%; for Generic2 - ; 30,6±6,%; 66,7±8,2%; 76,4±7,4%; ,8±5,%; 86,±,7%; ,6±,%: for Generic - 80,8±,6%; ,5±1,9%; , 8±,2%; ,±2,7%; ,9±2,1%; ,1±2,%; ,±2,4%; for Generic4 - ,5±1,7%; ,4±,8%; ,2±1,2%; , 9±,9%; ,9±,9%; ,9±,9%; ,8±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±

,6%; 40, 5±,%; 62,8±2,%; 80,±,1%; 85,4±2,9%; ,8±,4%; 80,9±,5%; for Generic1 - ; 67,±7,8%; 89,7±2,%; 91, 9±4,%; 89,1±1,6%; 88,±1,4%; 87,8±1,2%; for Generic2 - ; 42,2±5,6%; 75,1±7,%; ,±6,%; 88,4±,2%; 88, 6±1,%; 87,9±1,%; for Generic4 - 85,5±,5%; 85,6±,5%; ,7±,9%; ,7±,%; ,4±,%; ,4±,%; ,±,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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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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The applicability of a method for predicting 'bearing capacity increase'in reinforced sandy ground was examined using tests performed under various test conditions. It was found that the present method predicted, with reasonable accuracy, the bearing capacity increase in sandy ground, reinforced with stiff reinforcement. This method may not be applicable for sandy ground reinforced with extensible reinforcement due to the unsuccessful formation of a semirigid zone under the footing. An investigation into the settlement of a footing on reinforced sandy ground, at ultimate footing load condition, suggested that the settlement of footing for reaching peak footing load may be correlated to the 'deep-footing'and the 'wide-slab'mechanisms. That is, the ultimate settlement ratio between reinforced and unreinforced model sandy ground, SR_f, may be linearly correlated to 'BCR_D'and 'BCR_s', which represent 'deep-footing' and 'wide-slab'effects, respectively, on the ultimate bearing capacity increase in reinforced sandy ground.

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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), 8 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-,5α,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-,5α,6β-triol (4), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , 5 and 6 did not induce MCT-1 cell ALP activity at .1—10 μM. These results suggested that the OH groups at C-5 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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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.
5. 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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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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A new limit equilibrium analysis for assessing the stability of a reinforced embankment on soft clay against rotational undrained failure is presented. The analysis considers strain compatibility along the slip surface to deduce the tension mobilized in extensible reinforcement at collapse condition, and models strain softening of soils along the slip surface. The load extension responses of the reinforcement can be dependent on confinement by soils. Non-uniform increase in undrained cohesion during construction can be accounted for. The analysis yields a 'Safety Factor Curve' instead of a unique value for safety factor. A parametric study for illustrating the relevance of the proposed analysis is reported.

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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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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, 4, 6-trien--one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, 4-triazoline-, 5-dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The 5, 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin .

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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 8 weeks in 208 nonfamilial hypercholesterolemia patients (/ 161, 4/ 47). The baseline lipoprotein concentration and the intake of energy and lipids were not significantly different between subjects with / and those with 4/ phenotypes. After the dietary therapy plasma total cholesterol and low density lipoprotein cholesterol were significantly decreased in both phenotype groups (p<.05). The patients with 4/ 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 4/ by the Kruskal Wallis test (p=.041). The presence of 4/ predicted the degree of cholesterol reduction following dietary therapy.

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津田沼孵化場における過去9カ年間の総入卵数1,597,683個の孵化成績を検討して,次の結果を得た。
1. 受精率には明確な季節的変化がみられ,交配別にその様相を異にする。すなわち,同品種間交配では春(W:91.31%, N: 89.57%, : 86.32%)に最も高く,冬(W:85.09%, N:.72%, :.65%)がこれに次ぎ,夏(W:77.65%, N:.33%, :.85%)と秋(W:74.77%, N:.99%, :.04%)に低い。異品種間交配においては,春(WN:89.68%, NW:87.59%, WB:89.21%),夏(WN:86.33%, NW:.12%, WB:86.27%)の順に高く,秋(WN:.41%, NW:79.97%, WB:.53%)と冬(WN:80.48%, NW:80.50%, WB:.52%)には低い。
2. W,N及びの孵化率は86.40,85.55,.76%であるが,異品種間交配WN,NW及びWBの孵化率は87.37,86.37及び.87%で,WNはW及びNよりも,NWはNよりも優れ,WBはよりも良好であつた(P<.01)。またW,N,の健全雛率は79.93,78.99.77.79%であるが,これらの異品種間交配WN,NW及びWBのそれは,.61,.85,.05%で,いづれもその両親の属する品種の同品種間交配の場合よりも優れた成績(P<.01)を示した。これらの結果は艀化の中~後期における発育中止率及び弱雛率の低さに由来する。なお,WNとNWの正逆交配間では,正交配のWNが艀化率,健全雛率共に優れ(P<.01)ている。
. 春の孵化率は89.32%で最も高く,次いで冬の88.18%であり,秋(.33%)と夏(80.78%)は相当低い。健全雛率も同様に,春は86.09%で最も高く,以下冬(.%),秋(78.52%),夏(77.11%)の順であつた。
4. 健全雛1,130,629羽の性比は,雄50.47%(P<.01)であつた。

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Six full-length cDNAs encoding pig cytochrome P450 (CYP) enzymes, CYP1A1, CYP2A19, CYP2, CYP2C33v4, CYP2C49, and CYP21, were isolated and sequenced. The cDNA sequences of pig CYP1A1, CYP2A19, CYP2, CYP2C49, and CYP21 showed high similarity to human CYP1A1 (85.4%), CYP2A13 (88.6%), (.1%), CYP2C18 (85.%), and (.5%), respectively, and pig CYP2C33v4 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 CYP2C33v4 and > CYP2C49 > CYP1A1 and CYP2A19 > . In the kidney, the CYP2C33v4 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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Estriol antisera were raised and studied for the use in radioimmunoassay (RIA) of urinary estrogen as an aid of diagnosis of feto-placental function. Antisera to estriol-related six haptens, i.., estriol 16-glucuronide (-16-G), estriol 16-hemisuccinate (-16-succ), estriol 17-hemisuccinate (-17-succ), estriol 16, 17-dihemisuccinate (-16, 17-succ), estriol -carboxymethylether (--CME) and estriol -glucuronide (--G), were obtained by immunizing rabbits with the respective haptenbovine serum albumin (BSA) conjugate. Antiserum to -16-G-BSA reacted significantly with -16-G, C-17 conjugated estrogens and free estrogens. But it did not react with C- conjugated estrogens and other steroids. Similar properties were observed with antisera to -16-succ-BSA, -17-succ-BSA and -16, 17-succ-BSA, but their reactivities with C-16 or C-17 conjugated estrogens were slightly lower than that of anti--16-G-BSA serum. Among antisera which were raised against estriol linked to BSA via hemisuccinate varying in linking posirion, anti--16-succ-BSA serum highly reacted with -16-G, while anti--17-succ-BSA did with -17-G. Anti--16, 17-succ-BSA serum reacted with C-16 and C-17 conjugated estrogens to nearly the same extent. Antisera to both --CME-BSA and --G-BSA reacted with estrogens conjugated at C- position, but failed to react with C-16 or C-17 conjugated estrogens. The latter antiserum reacted more specifically with and -G than the former. Estrogen values in pregnancy urine samples estimated by the RIA by use of anti--16-G serum were not influenced by other components in urine, and showed a good correlation of y=.x-1.28, r=.983 with those determined by the currently available colorimetric method with -kit.

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