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．

抄録全体を表示

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, 18:4 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.

抄録全体を表示

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;;4) was performed. At first, we moved drugs from solution with pH .2 (.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%; 62,8±4,0%; 79,±2,%; ,±2,%; ,±2,%; ,±4,4%; for Generic - 0; 49,±,%; ,8 ±2,8%; 90,4±,7%; , 2±2,2%; 87,±2,0%; 85,±,%; for Generic2 - 0; 30,±,%; 66,7±8,2%; 76,4±7,4%; 82,8±,%; 86,0±,7%; 84,±,%: for Generic - ,8±,%; ,±,%; , 8±,2%; ,±2,7%; ,±2,%; 82,±2,0%; 82,0±2,4%; for Generic4 - 82,±,7%; 84,4±0,8%; 84,2±,2%; 82, ±0,%; 82,±0,%; 82,±0,%; 82,8±,%, 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,

%; 40, ±,0%; 62,8±2,0%; ,0±,%; 85,4±2,%; 82,8±,4%; ,±,%; for Generic - 0; 67,0±7,8%; 89,7±2,%; 91, ±4,%; 89,±,%; ,±,4%; 87,8±,2%; for Generic2 - 0; 42,2±,%; 75,±7,%; ,0±,0%; ,4±,2%; , ±,%; 87,±,0%; for Generic4 - 85,±0,%; 85,±0,%; 84,7±0,%; 82,7±,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.

抄録全体を表示

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.%, 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. type (株) GyrA (SL) ・ParC (SI), type2 (12株) GyrA (SL & D87N) ・ParC (SI), type (8株) GyrA (SL & D87N) ・ParC (SI & 84G) または (SR & 84V), type4 (4株) GyrA (SL & D87N) ・ParC (SI & 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typeでは, それぞれμg/mL, 2μg/mLおよび8μg/mL, type2では8～32μg/mL, 8～32μg/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～2カ所の変異がみられた.

抄録全体を表示

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～〕,〔a～〕,〔7a～〕,〔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-,4:,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.

抄録全体を表示

The numerical values of the intervals betrween optieal levels are competed for the configurations *

94s

,

5

s,

6

s 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 for

1

s, 2s, 2p,

3

s,

3

p and

3

d. Those of 4s,

5

s,

e

.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

抄録全体を表示

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=4) and CT (2.±.05, n=4), higher LEP (0.33±0.04, n=) and lower CTX- (0.48±0., n=) than C. The treatment of DIO with decreased CTX- (4.44±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=4). 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

抄録全体を表示

Circuit techniques to enhance the linearity of input-voltage-to-current (V/I) conversion and to increase the output impedance of a current source by compensating for the low intrinsic gain of a transistor were introduced to realize a high-frequency operational transconductance amplifier (OTA) for a low supply voltage using sub-100-nm CMOS processes. Applying these techniques, a MOS 7th-order Gm-C linear-phase low-pass filter (LPF) was realized using a 65nm CMOS process. A simplified biquad LPF that can serve as a component of a 7th-order LPF was newly developed by replacing OTAs with resistors. As a result, the -dB frequency bandwidth, group delay ripple, rd-order distortion, and rd-order input intercept point (IIP) were 200MHz, 2.2%, ≤ -55dB with a 100MHz input, and +10.dBm, respectively, all with a ±0.Vp-p input signal at each input terminal in the pseudodifferential configuration. The LPF including an output buffer dissipated 60mW in the case of a .2V supply. Wide spurious-free dynamic range (SFDR) characteristics were confirmed up to high frequencies.

抄録全体を表示

要旨：【背景】膝下重症下肢虚血に対する初回治療としてEVT を行うかバイパスを行うかは議論が分かれる．【目的】初回治療として下腿病変に対するEVT を行った群（ 群）と下腿足関節バイパスを行った群（ 群）の短期中期成績を検討する．さらに生命予後に関与する危険因子を検討し層別化を行う．【対象と方法】対象は2006 年11 月～2012 年7 月に重症虚血肢に対し下腿足関節領域の血行再建を行った全症例（150 例169 肢）とした．初回治療により 群（102 例118 肢）と 群（48 例51 肢）に分け検討した．【結果】平均観察期間は15 カ月であった．術前背景（年齢・性別・高血圧・糖尿病・虚血性心疾患・脳血管疾患・透析・心不全）は2 群間に有意な差を認めなかった．術後30 日成績は手術死亡 群.％ / 群0％，大切断 群.％ / 群.％ であった． 短期中期成績（ 年・ 年）は非大切断生存 群71.7％・41.％ / 群79.％・65.4％，生存率 群73.％・55.％ / 群.％・57.％，救肢率 群.8％・.2％ / 群91.0％・.％で両群間に有意差を認めなかった．多変量解析にて生存率に関与した因子は高齢（ 歳以上），虚血性心疾患合併・慢性心不全合併および非歩行であった．【結論】膝下病変に対するEVT は一期的自家静脈バイパスに適さないと考えられる症例に対して有用性がある．膝下重症下肢虚血患者における遠隔期死亡の独立した危険因子は高齢･虚血性心疾患合併・慢性心不全合併・非歩行であった．

抄録全体を表示

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.-.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.

抄録全体を表示

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.

抄録全体を表示

A total of 176

E

. coli isolates were retrieved from 203 diarrheic fecal samples collected from Korean cattle on 117 different farms. The most frequently observed resistance in

E

. coli isolates was to tetracycline (.%), followed by streptomycin (.7%) and ampicillin (64.8%). Resistance to cefazolin, cefoperazone, cefepime and amikacin was very low. Of the 176

E

. coli strains, forty (.7%) isolates from 30 farms showed resistance to fluoroquinolones (FQ). All the FQ-resistant strains possessed double mutations at codons and 87 in the gyrA gene, and a single mutation mostly at codon in the parC gene, except in one isolate. The pulsed-field gel electrophoresis profiles of the FQ-resistant

E

. coli isolates were heterogeneous, but two or three isolates that showed an identical pattern originated from the same or different farms. This study demonstrates that FQ resistance is frequently observed in

E

. coli from diarrheic cattle and that mutations in the quinolone resistance-determining region are the same as those seen in

E

. coli originating from other animal species and humans. The FQ resistance in diarrheic cattle might have been mostly acquired independently, although the possibility of transmission of FQ-resistant

E

. coli within a farm or between farms is plausible.

抄録全体を表示

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.

抄録全体を表示

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.

抄録全体を表示

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,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。

抄録全体を表示