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 (G

;2;;) was performed. At first, we moved drugs from solution with pH .2 (.2±0.05) to pH .0 (.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH exposure time of resistance to PDGR for omeprazole is minutes, i.. the active substance should not be released within minutes at pH . 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 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after

, 10, 15, 20, 30, 45, 60 minutes in pH solution at the first stage were different for OO and generics. For OO, these values were ,±0,%; 41,±,0%; 62,±,0%; 79,5±2,%; ,5±2,%; ,±2,%; 80,±,%; for Generic - 0; 49,±,%; 88, ±2,%; 90,±,%; 88, 2±2,2%; 87,±2,0%; 85,±,%; for Generic2 - 0; 30,±,%; 66,±,2%; 76,±,%; ,±5,%; 86,0±,%; 84,±,%: for Generic - 80,±,%; ,5±,%; , ±,2%; ,±2,%; ,±2,%; ,±2,0%; ,0±2,%; for Generic - ,5±,%; 84,±0,%; 84,2±,2%; , ±0,%; ,±0,%; ,±0,%; ,±,%, respectively.

An analysis of the omeprazole concentration in pH

solution at the second stage revealed the following parameters after the same time: for OO - ,±0,%; 40, 5±,0%; 62,±2,0%; 80,0±,%; 85,±2,%; ,±,%; 80,±,5%; for Generic - 0; 67,0±,%; 89,±2,%; 91, ±,%; 89,±,%; 88,±,%; 87,±,2%; for Generic2 - 0; 42,2±5,%; 75,±,%; ,0±,0%; 88,±,2%; 88, ±,%; 87,±,0%; for Generic - 85,5±0,5%; 85,±0,5%; 84,±0,%; ,±,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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Failure problems of saturated soils are classified in the present study into the following four types : Type I : The failure of loose and/or normally consolidated soils under fully drained loading conditions. Type II : The same soils but under perfectly undrained conditions. Type III : The failure of dense and/or overconsolidated soils under fully drained conditions. Type IV : The same soils but under perfectly undrained conditions. The soil-water coupling limiting equilibrium analysis on the basis of the critical state concept is shown possible to draw a distinction between type I, II and IV problems, and the limitations of the analysis procedure happen in solving the type problem in the above. This is demonstrated experimentally, in which seepage failure experiments in laboratory with the use of a saturated silty sand are employed to make distinctions clearly between the four types of failure problems. The definite distinctions both in failure load and failure mode appeared in the four types of experiments are summarized as follows : () the smallest failure load in loose sand in the undrained condition, (2) the largest failure load with the largest failure region in dense sand under undrained loading, () the observation of no global deformation before failure within the soil under the fully drained condition that suggests the development of very localized shear deformation in the sand. Three out of four experiments are described well by the limit analysis computation mentioned above as far as the failure load and the shape and the size of the failure region after boiling failure are concerned, and thus the type III problem is identified to be the problem that should be solved by any other means in near future.

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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 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 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 , '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 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 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 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 . Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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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-. Sixteen phosphate buffered saline (PBS), boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT- 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-,-diene-,5α,-triol (). induced ALP activities of MCT- 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- cells by , ergosterol (2), ergocalciferol (), cholesta-,5α,-triol (), -dehydrocholesterol (5) and cholecalciferol () were tested. The enzyme activities of MCT- cells were increased .0-fold by 10 μM and 2.-fold by 10 μM . However, 2, , 5 and did not induce MCT- cell ALP activity at 0.—10 μM. These results suggested that the OH groups at C-5 and/or C- of and played an important role in their differentiation-inducing activities on MCT- cells. Furthermore, suppressed induction of MCT- cell apoptosis by serum starvation.

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Two new polyacetylene compounds (, , 12)--acetoxy--isovaleryloxytetradeca-, , 12-trien-, 10-diyn-14-ol (), and (, , 12)--acetoxy--(2-methylbutyryloxy)tetradeca-, , 12-trien-, 10-diyn-14-ol (C) have been isolated along with (, , 12)--acetoxy--senecioyloxytetradeca-, , 12-trien-, 10-diyn-14-ol (A) from Atractylodes Rhizome (Karabyakujutu). The structures of these compounds were determined on the basis of their spectral data.

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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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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-[,2,,,5,,,,-

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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Fracture healing is a complex dynamic process that involves the balance between osteoblasts and osteoclasts. Several microRNAs (miRNAs) have been shown to participate in fracture healing. In this study, we investigated the role of miR-324-

p in osteoblast differentiation. MCT- cell differentiation was induced by icariin, and miR-324-p expression levels during cell differentiation were measured using qRT-PCR. Cell proliferation and differentiation were assessed to evaluate the function of miR-324-p. Luciferase activity was used for target gene verification. During MCT- differentiation, miR-324-p levels gradually increased over time. Further experiments showed that miR-324-p overexpression significantly promoted cell viability, whereas miR-324-p downregulation showed the opposite effect. For cells with miR-324-p mimic, the levels of bone sialoprotein, Runx2, osteocalcin, and alkaline phosphatase activity were significantly elevated. SMAD is the target gene of miR-324-p, and its level is gradually downregulated during MCT- cell differentiation. MiR-324-p may promote MCT- cell differentiation by targeting SMAD.

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. 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.
. 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.
. 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.
. 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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Limiting equilibrium state of saturated soils is solved taking into account drainage conditions during loading stage before reaching limit state. In analysis procedure, non-dilatant characteristics are assumed at limit state and then the failure problem discussed in the present study is concerned with normally consolidated and/or lightly overconsolidated soils. When solving statically indeterminate limiting equilibrium state one needs constitutive relations at limit state. In saturated soils, however, since the constitutive relations are generally expressed in terms of effective stresses, an additional field equation is required in order to link a velocity field to a pore pressure field. Therefore the problem should be solved as a coupling problem between these two fields. Two distinct types are discussed, one is undrained problem and the other, fully drained problem. Topics covered in the present study are as follows : () Undrained bearing capacity and excavation stability of soft clays, (2) Bearing capacity under partly drained and/or partly swelling condition, () Comparison between rapid loading condition and undrained condition, and () Seepage failure of loose sandy soils under fully drained condition.

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The filtration compatibility of soil-geotextile systems has been assessed experimentally in the laboratory with the gradient-ratio test. A nonwoven geotextile was used against a variety of model soils that were prepared from glass beads. They exhibited a range of fines content, in both gap-graded and broadly-graded size distributions. Filter blinding and clogging, if it happens, occurs within hours of initiating unidirectional flow. The zone of soil above the geotextile that is influenced is relatively thin. In gap-graded soils, the movement of fine particles appears to occur at a conditioh of />. A new dimensionless index is proposed to quantify the internal stability of gap-graded soils.

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The bearing capacity of plane strain model footings on sand is numerically investigated with a finite element method and a polar hypoplastic constitutive law. The constitutive law is obtained through an extension of a non-polar hypoplastic constitutive law by polar quantities : rotations, curvatures, couple stresses and a characteristic length. It can reproduce the salient features of granular bodies while taking into account shear localisation. The hypoplastic constants are calibrated with element test calculations on the basis of plane strain and triaxial compression tests. The FE-analyses are performed for both different mean grain diameters and initial densities of dry medium sand, and footing widths. The effect of material constants on the load-displacement curve is also investigated. The FE-results are compared with model tests. Advantages and limitations of a polar hypoplastic approach are outlined.

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