ラットに

3H

-CU-

83

(S)を25μg/kgで静脈内あるいは経口投与し，血液中濃度および尿糞中排泄を検討した．
静脈内投与後の血液中濃度推移は投与後

5

分より上昇し，投与後45分に25.74ng eq./mlのC_maxを示し，それ以後

t₁

/2

3

.05時間と

t₁

/2 33.09時間の二相で減少した．投与後72時間までのAUCは135.42ng eq.·hr/mlであった．
経口投与では，投与後

3

時間でC_max

4

.10ng eq./mlに達し，以後

t₁

/2α

4

.46時間と

t₁

/2β 26.

83

時間の二相で減少した．投与後72時間までのAUCは48.62ng eq.·hr/mlであった．
静脈内投与と経口投与のいずれの場合も，尿および糞中への放射能の排泄は，投与後48時間でほぼ終了した．静脈内投与では，投与後72時間までに投与量の30.52%が尿中に，60.42%が糞中に排泄された．経口投与では，同じく72時間までに40.34%が尿中に，69.24%が糞中に排泄された．

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The acetone extracts from three samples of the hepatopancreas of the poisonous scallops obtained on the Okhotsk Coast of Hokkaido Island were fractionated into two parts, hexane soluble fraction (fraction H) and 85% aqueous ethanol soluble fraction (fraction ) by partition to two layers. The majortoxic components in the mouse assay of “diarrheic shellfish toxin” by intra-peritoneal injection were found to be free unsaturated fatty acids showed the following toxicity in MU per g, 18: n- 35, 18:2 n- , 18: n- 167, 18: n- , 20: n- 167, and : n- , respectively. Toxicity of the fraction Hin MUper g was much lower than that of the fraction . However, the toxicity of the fraction H per g of the hepatopancreas was about twice that of the fraction , since the fraction Hwas much more abundant than the fraction in the hepatopancreas. The method for the assay of the diarrhetic shellfish toxin must be reexamined by considering the toxic effect of the free unsaturated fatty acids.

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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= 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 : () 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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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%; 62,8±,0%; 79,±2,%; ,±2,%; 81,±2,%; ,±,%; for Generic - 0; 49,±,%; ,8 ±2,8%; 90,±,%; , 2±2,2%; 87,±2,0%; 85,±,%; for Generic2 - 0; 30,±,%; 66,±8,2%; 76,±,%; ,8±,%; 86,0±,%; 84,±,%: for Generic - ,8±,%; ,±,%; , 8±,2%; ,±2,%; 81,±2,%; ,±2,0%; ,0±2,%; for Generic - ,±,%; 84,±0,8%; 84,2±,2%; , ±0,%; ,±0,%; ,±0,%; ,8±,%, 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, ±,0%; 62,8±2,0%; ,0±,%; 85,±2,%; ,8±,%; ,±,%; for Generic - 0; 67,0±,8%; 89,±2,%; 91, ±,%; 89,±,%; ,±,%; 87,8±,2%; for Generic2 - 0; 42,2±,%; 75,±,%; 81,0±,0%; ,±,2%; , ±,%; 87,±,0%; for Generic - 85,±0,%; 85,±0,%; 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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Activity-directed isolation of the ethyl acetate, methylene chloride and n-hexane fractions of Gloiopeltis furcata resulted in the isolation of 18 compounds. Their structures were elucidated as 2-(-hydroxy--oxotetrahydrofuran--yl)acetic acid (), glutaric acid (2), succinic acid (), nicotinic acid (), ()--hydroxyhex-2-enoic acid (), cholesterol (), -hydroxycholesterol (), uridine (8), glycerol (), -(hydroxymethyl)-2-methoxybenzene-,-diol (10), (,)--oxodeca-,-dienoic acid (11), (Z)--ethylidene--methylpyrrolidine-2,-dione (12), dehydrovomifoliol (13), loliolide (14), cholesteryl stearate (15), palmitic acid (16), cis-,8,11,14,17-eicosapentaenoic acid (17) and α-linolenic acid (18) on the basis of spectroscopic and chemical evidences. Their anticholinesterase and antioxidant activities were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as well as scavenging activities on ,-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO⁻). All isolated compounds (—18) exhibited moderate AChE inhibitory activities with IC₅₀ values ranging from .14—12.50 μg/ml, whereas , , , 17, and 18 showed mild BChE inhibitory activities with IC₅₀ values ranging from .57—15.89 μg/ml. Although most of the compounds isolated were lacking the scavenging activity on DPPH radical and ONOO⁻, and 10 showed good DPPH radical scavenging activity, and , 10, and 16 showed potent ONOO⁻ scavenging activity.

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性周期における牛の末梢血中遊離estrogen測定にITTRICH螢光法を応用して次の成績を得た。
Ittrich colorの最大波長をspectrofluorometer Hitachi MPF-2AおよびType203で測定した結果,励起光538nm,螢光552.nmであった。この螢光特性は, およびにそれぞれ共通であった。実際の測定では最大波長が接近しているので感度は若干低下するが510~520nmで励起し•螢光側552•±•を読み,ALLENの補正を行なった。この条件において,および-methyletherの最少検出量はであった。回収率補正の目的で加えた,-

3H

-

E₂

-17βの全過程における回収率は平均60.

3

±11.

7

%であった。正常性周期を示す黒毛和種2頭の頸静脈血についてestrogenを分画測定した。その結果,両牛共

E₁

,

E₂

の各消長型は性周期の全期間を通じてほぼ同じ傾向を示したが,

E₂

は

E₁

にくらべ全般に高値であった。また

E₃

は検出されなかった。これらの牛のtotalestrogenは発情前期に増加し,排卵前に鋭いピーク(35.

3

および99.8ng/l;

E₁5.9

および16.0ng/l,

E₂29.4

および

83.8ng

/l)を形成し,排卵後は急激に減少して最低値(

3

.8~

5.3ng

/l;

E₁1.6

および

1.9ng

/l,

E₂2.2

および

3.4ng

/l)を示した。黄体期の最高値(10.

1

および27.0ng/l;

E₁2.4

および

3.4ng

/l,

E₂7.7

および

23.6ng

/l)は排卵後

6

~8日に認めた。すなわちestrogenの血中濃度は性周期の間に2つのピークを形成することを認めた。

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Plate anchors are the popular type of anchors used in civil engineering construction both on land and offshore. In this paper, the uplift capacity of plate anchor in a sloped clayey ground has been brought out with the help of an experimental programme, carried out on a 50mm diameter model plate anchor. The tests have been conducted at slopes of O°, 15°, 30°and 45°. From the test results, it is found that in the case of shallow anchor, as the slope is increasing from O°to 45°, there seems to be a reduction in uplift capacity. Simple expressions are suggested to arrive at the uplift capacities in sloped ground. The mechanisms involved in the reduction of capacity with slope are explained based on the observed behaviour.

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Laboratory model test results for the holding capacity of inclined shallow square plate anchors in clay (φ=0 concept) have been presented. The inclination of the anchor with respect to the horizontal was varied from zero to 90°. Based on the model study, an empirical relationship for estimating the ultimate holding capacity of the anchors has been presented.

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Background: Exenatide (EXE), a prototypical GLP-

R agonist, has been reported as beneficial to the balance of bone turnover in hyperlipidic and hyperglucidic diet-induced obesity in rats (DIO). Objective: To identify the mediation by GLP-R of insulin (INS), leptin (LEP), osteocalcin (OCN), calcitonin (CT), carboxy-terminal telopeptide of type collagen (CTX-), procollagen type amino-terminal propeptide (PNP) and bone mineral density of femur (BMDF) in DIO. Methods: 72-75-day-old male rats had access only to (i) hyperlipidic food (.2 kcal/g) and 30% sucrose solution for drinking (.2 kcal/mL), or (ii) received normocaloric diet ( kcal/g) and were allowed to feed and to drink water

ad

libitum. 122-125-day-old rats with 20% overweight were selected from i as obese and those with normal weight were selected from ii as control (C) animals. Thus, obese animals remained untreated (DIO) or were treated sc with 100μg of the competitive antagonist of GLP-R, exendin (-39) () per kg (DIO-) daily, for 20 days. Plasma INS, LEP, OCN, CTX- (ng/mL), CT and PNP (pg/mL) were measured by ELISA. BMDF (g/) was measured by X-rays. Results: DIO exhibited similar INS (12.90±., n=) and CT (2.±.05, n=), higher LEP (0.33±0.04, n=) and lower CTX- (0.48±0., n=) than C. The treatment of DIO with decreased CTX- (.44±0.63, n=) and increased PNP (163.40±39., n=). DIO- decreased INS (.75±.50, n=) in relation to DIO, at the same level than C (10.58±.49, n=). LEP level in DIO- (0.23±0.02, n=) was intermediate in relation to DIO and C (0.16±0.05, n=). OCN, CT and BMDF were similar among C, DIO and DIO-. Conclusions: Decreased CTX- and normal OCN, PNP and BMDF reflect a relative normal balance in bone turnover in DIO. Since decreases CTX-, a known effect of EXE in DIO, this alteration on CTX- extrapolates the GLP-R binding and/or EXE and act as selective modulators with different actions in different targets. Furthermore, increases PNP (not affected by EXE) and does not affect CT (increased by EXE). effects in DIO imply in increased osteoblastic and decreased osteoclastic activities, which promote an imbalance of bone turnover.

Supported by FAPESP, CNPq and CAPES

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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), 8 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-,,-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-,,-triol (), -dehydrocholesterol () 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, , and did not induce MCT- cell ALP activity at 0.—10 μM. These results suggested that the OH groups at C- 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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Nアルキル,:,10-ペリレンテトラカルボン酸モノアンヒドリド=モノイミド[a～]と芳香族アミン(アニリン,p-トルイジン,p-アニシジン,,-キシリジン,-アミノナゾベンゼン,およびo-フェニレンジアミン)を縮合して非対称型,:,10-ペリレンビス(ジカルボキシミド)誘導体-N-アルキル-N'-アリール-,:,10-ペリレンビス(ジカルボキシミド)(〔a～〕,〔a～〕,〔a～〕,〔8a～〕,〔a～〕,および〔10a～〕)を合成した. これらの各誘導体はすべて赤色系の色相を示し, 顔料試験の結果N-ブチル-N'-アリール-,:,10-ペリレンビス(ジカルボキシミド)(たとえば〔〕や〔〕)がとくにすぐれた耐光性を示した.

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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 (), were isolated together with 11 known saponins from the saponin fraction. The chemical structures of — 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 .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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Virus-like particles (VLPs) were collected from geothermal vent water samples in the drift-way at Toyoha Mine, Hokkaido, Japan (−500 m level, 63.°C) whose VLP and bacterial abundance was (No/ml±SD, n: 500), VLP: .60±0.29×10⁸ and bacteria: .61±0.14×10⁶. VLPs ranged in diameter from 30 to 320 nm, and the major size distribution (ca 62%) was .33. nm (n: 843). Ultrafiltration followed by CsCl density equilibrium ultracentrifugation gave purified TY-VLPs: .64×10¹³. Regardless of UV treatment, TY-VLP reduced the efficiency of plating to 68.-.% at a multiplicity of infection of ca 0. on Escherichia coli AB1157. Generalised transduction was observed on

E

. coli AB1157 with a frequency between 10-

4

and 10-

5

cells/particle using TY-VLPs without UV-treatment. The growth of generated

E

. coli transductants (TY-

E

-trans) was compared to that of an

E

. coli transductant (ST-

E

-trans) generated by Aquificales originating VLP (Chiura, 2002). The extent of the maximum growth of both transductants was ca 40% of the parental

E

. coli used as a recipient. TY-

E

-trans acquired "budding-like" particle productivity, which has been demonstrated for ST-

E

-trans. ST-

E

-trans produced five different size particles, whose DNA content ranged between 291.

6

and 382.0 kb, and TY-

E

-trans produced ten different size particles between 68.

5

and 190.2 kb, respectively.

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