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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Backgrounds: It has been reported that somatic mutations of mitochondrial DNA (mtDNA) is related with aging, or development of cardiovascular disease. We hypothesized that mtDNA4977 deletion mutation (4977-) detected from human blood contributes to atrial dysfunction in patients with . Methods: We studied for mtDNA4977- in 183 patients with non-valvular , (127 PAF, 56 PeAF) and 69 patients with healthy control. The detection of mtDNA4977- was determined by Gene Scan. Results: . The mtDNA4977- in patients were older than those without mutation (61.±.2 vs. 51.±., p<0.0001). 2. Frequency of mtDNA4977- mutation in patients with ≤45 years old was not different to age matched control (.% vs. 11.%, p=0.2371). . The mtDNA4977- had higher /, (11.±. vs. .±., p=0.0005), plasma levels of TIMP- (.51±0.77 vs. .28±0.57 ng/mL, p=0.0210) and ANP (.11±2.67 vs. .91±2.01 nmole/L, p=0.0010), and were more frequently taking statin (27.2% vs. .%, p=0.0055) than those without mutation. . .% with mtDNA4977- and 85.5% without mtDNA4977- remain in sinus rhythm 12.±5. months after RFCA (p=0.3008). Conclusion: mtDNA4977- was related with aging, diastolic dysfunction, serologic markers related with atrial remodeling or pressure overloading. Its frequency was not different to age matched patients with control, and did not affect the clinical outcome after RFCA.

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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 (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,%; 81,±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,%; 81,±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±,%; ,±2,%; 91, ±,%; ,±,%; 88,±,%; 87,±,2%; for Generic2 - 0; 42,2±5,%; 75,±,%; 81,0±,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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The correction factor (η_ie) for the ultimate bearing capacity of a footing placed adjacent to a slope, taking into account the combined effect of horizontal and vertical seismic loads, represented by horizontal and vertical seismic coefficients, k_h and k_v, respectively, was derived using a modified Janbu's slice method. The influence of slope angles ‘α’ on the values of ‘η_ie’ are studied here. It was found that the values of η_ie can be expressed as an exponential function of ‘k_h/(-k_v)’ and ‘α’, with a measurable interdependency between ‘α’ and ‘η_ie’. The influence of ‘α’ on the value of ‘η_ie’ increases as the input value of ‘k_h/(-k_v)’ increases. Equations derived based on the analytical results are proposed to account for this effect. Based on the analyses of 11 near-fault seismographers obtained in the 1999 Chi-Chi earthquake in Taiwan, a ratio between the vertical and the horizontal seismic coefficients, λ, of between ±0.25 is suggested for including the combined effect of vertical and horizontal seismic forces in evaluating the seismic bearing capacity of footings located in near-fault areas.

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At present, analytical or empirical formula for seismic bearing capacity of footings adjacent to slopes is not available. This study uses a pseudo-static-based approach in conjunction with rigorous Janbu's slice method to derive analytical values of seismic bearing capacity factors (N_γ) and correction factors for the effects of inertia of soil mass and load inclinations for a rigid footing adjacent to cohesionless slopes. It is shown that both the bearing capacity factors (N_γ) and the correction factors for the seismic bearing capacity of footings placed on level ground derived herein are comparable with those reported in the literature. Empirical equations regarding the effects of slope angles and load inclinations, expressed using generalized forms of those proposed in the literature, are also derived. It is also found that the empirical equations derived in the present study provide values of correction factors in good agreements with the analytical ones, indicating the validity of using these empirical equations for assessing the bearing capacity of rigid footings situated on the slope subjected to pseudo-static seismic loading.

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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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Chemical synthesis of (, 24R)- and (, 24S)-, 24-dihydroxy--vitamin has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the -hydroxy group by a reduction of the , 2-epoxide generated by epoxidation of the , , -trien--one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the bond by standard methods and its protection with -phenyl-, 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, -dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-, 24-hydroxyvitamin compound bound equally well to the chick intestinal cytosol receptor as , 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than , 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of , 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 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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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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(,)-2,-エポキシ-,,11,11-テトラメチルシクロウンデカ-,-ジエン(2)をフムレン((2,,)-,,11,11-テトラメチルシクロウンデカ-2,,-トリエン)より合成する既知の合成法は実際に牧率が低く合成的に問題がある.さらに,2の合成はその反応性や物性の研究のために簡単に高牧率で行われることが望まれる.今回,2の新たな合成法と簡便な精製法を見いだし,2を高牧率でから合成することができたので報告する.のジエポキシ化,続く再結晶により得られたジエポキシド()は二価のチタンにより還元されて,(273%)と(25%)と少量のを含む2を主生成物(42.%)として与えた.とは原料として再利用できる.2の精製はと同様硝酸銀()錯体の結晶で行い,純粋な2はから通算牧率32.0%で得られた.2の既知方法による合成は段階の反応と数回のカラム分離及び10%含浸シリカゲルカラム分離を必要とし牧率が極端に低い.今回,新しい2の合成法は2段階の反応で回のカラム分離と再結晶により高い通算牧率を示す.

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The saponin fraction from the seeds of the tea plant [Camellia sinensis (L.) O. KUNTZE (Theaceae)] was found to exhibit potent protective effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats. Five new triterpene saponins, theasaponins (), (2), (), (), and (5), were isolated together with 11 known saponins from the saponin fraction. The chemical structures of —5 were elucidated on the basis of chemical and physicochemical evidence. Among the isolated saponins, theasaponins (), (), and () and assamsaponin C (10) showed an inhibitory effect on ethanol-induced gastric mucosal lesions at a dose of 5.0 mg/kg, p.o. and their activities were stronger than that of omeplazole. With regard to the structure–activity relationships of theasaponins, the following structural requirements for a protective effect on ethanol-induced gastric lesions were suggested; ) the 21- and/or -acyl groups are essential for the activity, 2) acetylation of the 16-hydroxyl group reduce the activity.

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