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t_1/2

3

.05時間とt_1/2 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t_1/2α 4.46時間とt_1/2β 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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A structure analysis of has been carried out to determine the deuterium trap sites by neutron powder diffraction with the Rietveld profile analysis. It is revealed that the deuterium atoms are located at octahedral () sites surrounded by six Ti atoms in the crystal structure of , space group P6₃/mcm. Local vibration spectra of hydrogen in measured by neutron inelastic scattering support this result; the energy eigenvalue of the primary vibration mode is found at 7.53 kJ/mol (78 meV). The hole radius and the spring constant of the Ti-H() bond are discussed.

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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, 18:1 n- 35, 18:2 n-6 , 18: n- 167, 18:4 n- , 20: n- 167, and :6 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 1 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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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±0.05) to pH 7.0 (7.0±0.05) 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 (4.0±0.05), 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±0,7%; 41,4±

,0%; 62,±4,0%; 79,±2,%; ,±2,%; 81,6±2,%; 80,6±4,4%; for Generic1 - 0; 49,±,%; , ±2,%; 90,4±,7%; , 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,%; 66,7±,2%; 76,4±7,4%; ,±,%; 86,0±,7%; 84,6±,%: for Generic - 80,±,6%; ,±1,%; , ±,2%; ,±2,7%; 81,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,±1,7%; 84,4±0,%; 84,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,±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±0,6%; 40,

±,0%; 62,±2,0%; 80,0±,1%; 85,4±2,%; ,±,4%; 80,±,%; for Generic1 - 0; 67,0±7,%; 89,7±2,%; 91, ±4,%; 89,1±1,6%; ,±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±,6%; 75,1±7,%; 81,0±6,0%; ,4±,2%; , 6±1,%; 87,±1,0%; for Generic4 - 85,±0,%; 85,6±0,%; 84,7±0,%; ,7±,0%; 84,4±0,%; 84,4±0,%; 84,±0,4%, 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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A structure analysis of has been carried out to determine the deuterium trap sites by neutron powder diffraction with the Rietveld profile analysis. It is revealed that the deuterium atoms are located at octahedral (2) sites surrounded by six Ti atoms in the crystal structure of , space group P6₃/mcm. Local vibration spectrum of hydrogen in measured by neutron inelastic scattering supports this result; the energy eigenvalue of the primary vibration mode is found at 7.53 kJ/mol (78 meV). The hole radius and the spring constant of the Ti–H() bond are discussed.

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1991年～2005年の福井県など4県における散発下痢症患者由来の大腸菌0153107株について, 市販の薬剤感受性ディスクを用いたKB (Kirby-Bauer) 法で12剤の薬剤感受性を調べた. 薬剤別耐性菌出現率はampicillinが72.%, streptomycinが48.6%, tetracyclinおよびsulfisoxazoleが46.7%, nalidixic acid (NA) が29.%およびciprofloxacin (CPFX) が24.%などであった. 7～10剤に耐性を示す18株中16株など計26株が, NAおよびCPFXに耐性を示した. NAおよびCPFXに耐性を示した24株とNAに耐性を示した1株について, gyrAおよびparC遺伝子の解析を行った結果, 次の4typesに分けられた. type1 (1株) GyrA (SL) ・ParC (S80I), type2 (12株) GyrA (SL & 87N) ・ParC (S80I), type (株) GyrA (SL & 87N) ・ParC (S80I & 84G) または (S80R & 84V), type4 (4株) GyrA (SL & 87N) ・ParC (S80I & A108T). アミノ酸変異とfluoroquinolone (FQ) 系薬剤の最小発育阻止濃度 (MIC) との関連をみると, CPFX, ofioxacinおよびnorfloxacinのMICはtype1では, それぞれ1μg/mL, 2μg/mLおよびμg/mL, type2では～32μg/mL, ～32μg/mLおよび16～256μg/mL, type, 4では32～256μg/mL, 32～128μg/mLおよび128～>512μg/mLであった. 患者由来のFQ系剤耐性大腸菌O153が多剤耐性傾向を示すとともに, gyrAおよびparCで各々1～2カ所の変異がみられた.

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本検討は, 経皮的冠動脈形成術 (PCI) 後の翌日血液透析 (HD) 時における透析中低血圧 (IDH) の発生因子について検討した. 対象は待機的PCI後, 翌日HDを施行した慢性HD患者連続

名 (年齢70±7歳, 男性64名). IDHの定義は, 収縮期血圧20mmHg以上の低下で, 症状を伴いかつHD中断を要したものとした. また, HD記録よりIDHを後方視的に調査し, Logistic回帰分析にてIDHの予測因子を検討した. IDH群 (12名) は非IDH群 (71名) に比して, 有意に低体重 (52.0±. vs. 62.±1.kg; p=0.007), 造影剤量/体重が多く (2.±0. vs. 1.±0.1mL/kg; p=0.018), 低左室駆出率で (45.±4.2 vs. 56.0±1.% ; p=0.030), /’ が高値 (.±. vs. 17.2±0.cm/sec; p=0.038) であった. また, 冠動脈病変や侵襲的な治療について有意差は認めなかった. Logistic回帰分析では, 造影剤量/体重 (OR, 6.87; 95%CI, 1.-25.; p=0.004) がIDHの有意な予測因子であった. 造影剤使用量が多い症例は, IDHを生じる危険性が高いことが示唆された.

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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.°) 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: 6.64×10¹³. Regardless of UV treatment, TY-VLP reduced the efficiency of plating to 68.6-.4% 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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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1ngであった。回収率補正の目的で加えた6,7-

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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Nアルキル,4:,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[4a～]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,4-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,4:,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-,4:,10-ペリレンビス(ジカルボキシミド)(〔a～〕,〔6a～〕,〔7a～〕,〔a～〕,〔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-,4:,10-ペリレンビス(ジカルボキシミド)(たとえば〔〕や〔6〕)がとくにすぐれた耐光性を示した.

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The numerical values of the intervals betrween optieal levels are competed for the configurations *⁹4s, s, 6s and 7s of Cu⁺, according to the general expression of energy-levels derived in the previous paper The self-consistent field radial functions computed by Hartree adn Hartree are used for1s, 2s, 2p, s, p and . Those of 4s, s, .s and are ealenlated from Hartree Hartree's core-functions by the numerical integrations. The calculated results are shown in Table I.The agreement with experiment is satisfactory

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The EISCAT Svalbard Radar (ESR) has been used to obtain ion velocities in the lower thermosphere. By using beam swinging and assuming homogeneity and stationarity of the plasma, first approximations to the electric field have been deduced, and thus the thermospheric neutral wind has been estimated. From these derived parameters, we have estimated the gradient Richardson Number. Although many assumptions must be made, there is an indication that electrodynamics is able to contribute to enhancement or even production of neutral-air turbulence in the lower thermosphere. Finally, we outline a proposal for an analogy to the Reynolds Number, but reflecting the relative importance's of the contribution of ion-drag to the neutral dynamics and the kinematic viscosity.

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Background: Exenatide (EXE), a prototypical GLP-1R 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-1R of insulin (INS), leptin (LEP), osteocalcin (OCN), calcitonin (CT), carboxy-terminal telopeptide of type 1 collagen (CTX-1), procollagen type 1 amino-terminal propeptide (P1NP) 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 (1.2 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 () animals. Thus, obese animals remained untreated (DIO) or were treated sc with 100μg of the competitive antagonist of GLP-1R, exendin (-39) () per kg (DIO-) daily, for 20 days. Plasma INS, LEP, OCN, CTX-1 (ng/mL), CT and P1NP (pg/mL) were measured by ELISA. BMDF (g/) was measured by X-rays. Results: DIO exhibited similar INS (12.90±1., n=4) and CT (2.80±1.05, n=4), higher LEP (0.33±0.04, n=) and lower CTX-1 (0.48±0., n=) than . The treatment of DIO with decreased CTX-1 (4.44±0.63, n=) and increased P1NP (163.40±39.80, n=). DIO- decreased INS (.75±1.50, n=) in relation to DIO, at the same level than (10.58±1.49, n=4). LEP level in DIO- (0.23±0.02, n=) was intermediate in relation to DIO and (0.16±0.05, n=). OCN, CT and BMDF were similar among , DIO and DIO-. Conclusions: Decreased CTX-1 and normal OCN, P1NP and BMDF reflect a relative normal balance in bone turnover in DIO. Since decreases CTX-1, a known effect of EXE in DIO, this alteration on CTX-1 extrapolates the GLP-1R binding and/or EXE and act as selective modulators with different actions in different targets. Furthermore, increases P1NP (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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Clinical results of rotator cuff repairs using the same therapeutic exercises from an early stage after surgery were investigated and compared with the preoperative X-ray findings. 70 shoulders with rotator cuff tears treated operatively and followed by active-assistive exercises in a supine position from 1 week and active exercises standing from weeks after surgery were evaluated. The average age was 63 years old and follow-up periods were 11. months. The operative procedures were McLaughlin's method in 41 shoulders, side to side sutures in , acromioplasty in 17 and a tendon transfer in . The preoperative X-ray findings were classified into groups: group A, superiorly migrated humeral head and narrowed joint space in 4 shoulders; group , only superior migration in 7; group , only narrowed joint space in ; group , no changes in 36; group , subacromial spurs more than mm without superior migration in 20. The postoperative results were assessed according to the JOA score and the failure rate of each group was investigated. No significant differences in the preoperative JOA score were found in the groups. The postoperative JOA scores were 62.±.6 in group A, 75.1±12.6 in , 78.0±12.2 in , 90.4±7. in , and .6±11.1 in . Especially groups and treated by McLaughlin's methods showed a significant higher score at follow-up. Rotator cuff repairs with the same therapeutic exercises from an early stage after surgery for groups A, and showed poor results. Groups A and with a superior migration of the humeral head showed a high failure rate of 40 % compared with 4.7% in group , and with no superior migration. For these cases more careful postoperative exercises were recommended.

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