Background: Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and

and main carotenoids with all-cause mortality in Japanese men and women.

Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had

,795 men and 35,539 women, aged 40–79 years at baseline (1988–1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009.

Results: There were 6,179 deaths in men and 5,355 deaths in women during the median follow-up of 18.

years for men and 19. years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were .83 (95% confidence interval [CI], .76–.90; P for trend < .0001) for vitamin C, . (95% CI, .78–.; P for trend < .0001) for vitamin , .88 (95% CI, .–.96; P for trend = .0006) for β-carotene, and .90 (95% CI, .–.98; P for trend = .0002) for β-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12–17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin , and β-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers.

Conclusions: Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.

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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±.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 minutes, i.. the active substance should not be released within minutes at pH 7. The exposure at the second stage was conducted with pH (.±.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±,7%; 41,±,%; 62,8±,%; 79,5±2,%; 83,5±2,%; ,6±2,%; 80,6±,%; for Generic1 - ; 49,±,%; 88,8 ±2,8%; 90,±,7%; 88, 2±2,2%; 87,±2,%; ,±1,1%; for Generic2 - ; 30,6±6,%; 66,7±8,2%; 76,±7,%; ,8±5,%; 86,±,7%; 84,6±,%: for Generic - 80,8±,6%; 83,5±1,%; 83, 8±,2%; 83,±2,7%; ,±2,1%; ,1±2,%; ,±2,%; for Generic - ,5±1,7%; 84,±,8%; 84,2±1,2%; , ±,%; ,±,%; ,±,%; ,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 -

,±,6%; 40, 5±,%; 62,8±2,%; 80,±,1%; ,±2,%; ,8±,%; 80,±,5%; for Generic1 - ; 67,±7,8%; 89,7±2,%; 91, ±,%; 89,1±1,6%; 88,±1,%; 87,8±1,2%; for Generic2 - ; 42,2±5,6%; 75,1±7,%; ,±6,%; 88,±,2%; 88, 6±1,%; 87,±1,%; for Generic - ,5±,5%; ,6±,5%; 84,7±,%; ,7±,%; 84,±,%; 84,±,%; 84,±,%, 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, CYP2B, CYP2C33v, CYP2C49, and CYP21, were isolated and sequenced. The cDNA sequences of pig CYP1A1, CYP2A19, CYP2B, CYP2C49, and CYP21 showed high similarity to human CYP1A1 (.%), CYP2A13 (88.6%), CYP2B6 (.1%), CYP2C18 (.%), and (.5%), 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 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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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, / 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<.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=.041). The presence of / predicted the degree of cholesterol reduction following dietary therapy.

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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 (), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .-fold by 10 μM 1 and 2.-fold by 10 μM . 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 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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This paper applies the fuzzy cluster analysis to six international stock markets (i.., France, Germany, the U.S., Canada, Japan, and China). We analyze the similarity values calculated from the monthly stock returns, using both Zadeh's and Ward's clustering methods. These two methods induce different partition trees. Both the Minkowski distance and cophenetic correlation coefficient choose Zadeh's method over Ward's method. The optimal partition tree and the associated optimal number of clusters suggest (1) the similarity of European countries, (2) the institutional regularity of the Chinese stock market, and () the strong influence of the U.S. These implications are consistent with standard economic theory, and are preserved under the addition of three countries (i.., the U.K., Mexico, and South Korea).

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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,,,5,6,7,8,-

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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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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This paper outlines a mathematical description of the stress dilatancy behaviour of granular materials which accounts for stress level and void ratio dependencies. The consideration of these aspects has important implications in the modelling of granular material behaviour. In fact, granular material mechanical response is largely dominated by the evolution of dilatancy, fabric and void ratio histories. The starting point in this study is the well established Rowe's theory which is revisited and ultimately modified by introducing a factor linked to governing state parameters in order to describe the complete behaviour of granular materials during deformation. Numerical simulations of triaxial tests on granular materials at different void ratios and stress levels are herein presented to illustrate the model.

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N-(2-フルオレニル) -マレイミド (I), N-1-(-アセトキシナフチル) -マレイミド (II), N-2-(-アセトキシフルオレニル) -マレイミド (III) の単独重合, 共重合をアゾビスイソブチロニトリル (IV) を開始剤としてテトラヒドロフラン中, 60℃で行った. 単独重合の初速度 (R_p) は, R_p=k [I] ^2.11 [IV]

0.64

, R_p=k [II] ^2.26 [IV]

0.72

, R_p=k [III] ^1.76 [IV]

0.52

となった. kは速度定数である. 全重合の活性化エネルギー (

E

), 頻度係数 (A) は

E

=26.

4

kcal/mol (I), 23.

3

kcal/mol (II),

22

.8kcal/mol (III), A=

3

.

4

×10¹⁵ (I), 2.7×10¹¹ (II), 1.5×10¹¹ (III) となった. またN置換マレイミドとメタクリル酸メチル (V) との共重合におけるモノマー反応性比, Q,

e

値を次のように決定した.
I (M₁) -V (M₂) 系で, r₁=

0

.24, r₂=

0

.

93

, Q₁=

0

.43,

e₁

=1.

82

, II (M₁) -V (M₂) 系で, r₁=

0

.17,

r₂2.29

, Q₁=

0

.51,

e₁

=1.37, III (M₁) -V (M₂) 系で, r₁=

0

.068, r₂=1.34, Q₁=

0

.87,

e₁

=1.90となった.

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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, , 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, -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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In order to clarify the physiological role of antidiuretic hormone (ADH) in regulating the renal water handling, a bioassay for ADH in urine was devised, and urinary excretion of ADH was determined in 21 normal subjects, 14 patients with central diabetes insipidus, and 8 patients with inappropriate secretion of ADH (SIADH). Under normally hydrated states, 12 normal subjects and 7 patients with central diabetes insipidus excreted .±.2mU of ADH/day (12.±/ml) (mean±s. .), and less than 8.2mU/day (/ml), respectively. 8 patients with SIADH excreted ADH ranging from 15.6 to 808.2mU/day. Under dehydrated states, ADH excretion increased to .±.5mU/hr (137.±/ml) (mean±S. .) in normal subjects. At that time, plasma and urine osmolality increased to 282.5±1.1 and 1004±43mOsm/kg (mean±S. .), respectively. In all of 7 patients with central diabetes insipidus, urinary ADH could be detected when plasma osmolality increased to 298.±1.7 mOsm/kg (mean±S. .) after water deprivation. In normal subjects, urinary ADH excretion decreased after water loading from .±.5 mU/hr to below .6mU/ hr (/ml) with a concurrent reduction of plasma and urine osmolality to 274.8±1. and ±7mOsm/kg (mean±S. .), respectively. Two types of daily urinary excretion patterns of ADH were found in patients with SIADH. One of them had ectopic ADH producing tumor and excreted a relatively large amount of ADH, and the other was a non-tumor case which excreted a normal amount of ADH. However, either case showed no suppressibility of ADH in the face of an expansion of body fluid with hypo-osmolality of the plasma.

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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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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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