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;3;4) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±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 4 minutes, i.. the active substance should not be released within 4 minutes at pH . 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 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 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 4,±0,%; 41,4±3,0%; 62,±4,0%; 79,±2,%; ,±2,%; ,6±2,%; 80,6±4,4%; for Generic1 - 0; 49,3±,%; , ±2,%; 90,4±3,%; , 2±2,2%; 87,3±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,3%; 66,±,2%; 76,4±,4%; 82,±,3%; 86,0±3,%; 84,6±3,3%: for Generic3 - 80,±3,6%; ,±1,%; , ±3,2%; ,3±2,%; ,±2,1%; 82,1±2,0%; 82,0±2,4%; for Generic4 - 82,±1,%; 84,4±0,%; 84,2±1,2%; 82, ±0,%; 82,±0,%; 82,±0,%; 82,±1,1%, respectively.

An analysis of the omeprazole concentration in pH

solution at the second stage revealed the following parameters after the same time: for OO - 4,4±0,6%; 40, ±3,0%; 62,±2,0%; 80,0±3,1%; 85,4±2,%; 82,±3,4%; 80,±3,%; for Generic1 - 0; 67,0±,%; 89,±2,3%; , ±4,3%; 89,1±1,6%; ,3±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±,6%; 75,1±,3%; ,0±6,0%; ,4±3,2%; , 6±1,3%; 87,±1,0%; for Generic4 - 85,±0,%; 85,6±0,%; 84,±0,%; 82,±3,0%; 84,4±0,3%; 84,4±0,3%; 84,3±0,4%, respectively. Generic3 release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic3 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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Repetitive liquefactions in angular and subangular gravels from an alluvial fan, in the case of two earthquakes with accelerations lower than that of a former which had caused liquefaction some months before, are described. The liquefaction took place from the surface, down to a depth of approximately 10 m. Water laden with sediments spouted out for some tens of minutes after the strong motion ceased. Knowledge of the grain size distribution of the sediments inside the body of the alluvial fan roughly defines the areas of the fan prone to future liquefaction. Non-repetitive liquefaction in overconsolidated fine fluvio-lacustrine sand of glacial origin at the unusual depth of 14 m to 16 m is also described. From the observation of sand lifted up for 10 m inside a large diameter well, and of that which spouted out from several microvents, it was estimated that extra-pore pressure was close to lithostatic conditions. Nevertheless, modeling of intrinsic pore pressure buildup on the DESRA2 programme gives lower values than the experimental one. Geotechnical characteristics of the 12 m-thick sandy stratum indicate that the upper part is unusually soft, either due to water circulation or past repetitive liquefactions which prevented reconsolidation. It is suggested that excess pore pressure generated by the earthquake was also due to redistribution of pressure from adjacent sediments.

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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 th-order Gm- 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 th-order LPF was newly developed by replacing OTAs with resistors. As a result, the -3dB frequency bandwidth, group delay ripple, 3rd-order distortion, and 3rd-order input intercept point (IIP3) were 200MHz, 2.2%, ≤ -55dB with a 100MHz input, and +10.3dBm, respectively, all with a ±0.1Vp-p input signal at each input terminal in the pseudodifferential configuration. The LPF including an output buffer dissipated 60mW in the case of a 1.2V supply. Wide spurious-free dynamic range (SFDR) characteristics were confirmed up to high frequencies.

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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-[1,2,3,4,

5

,6,

7

,

8

,

9

-

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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魚市場およびと畜場のドブネズミにおけるStaphylococcus auresの保有率はそれぞれ74.6% (44/59), 34.6% (/26) であった. 魚市場のネズミ由来S. aureus104株の生物型は型株 (77.%), B型16株 (15.4%), A型6株 (.%), 型別不能1株 (1%) で, と畜場由来株はG型株 (.%), B型1株 (11.1%) であった. 魚市場のネズミ由来株のコアグラーゼ型は, VIII型 (26.%), 1型 (.1%), VII型 (13.%), IV型 (.%), II型 (.%), III型 (2.%), V型 (2.%), VI型 (2.%), 同定不能 (14.4%) で, と畜場由来株は, VIII型 (44.4%), V型 (.2%), VI [型 (.2%), 同定不能 (11.1%) であった.魚市場のネズミ匹由来の12株からはエンテロトキシンA (11株) およびB (1株) が産生された.

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A full account is given of the chemical behavior observed for , -dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, b, d, (X=I), 16 (X=Br), and 16f (X=ClO₄) rearranged to isomeric N⁶, -dialkyladenines (21a-f) in 50-% yields. Treatment of the salts with 0.N aqueous Na₂CO₃ at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in H₂O at room temperature gave the ring-opened derivatives a-f (in the trans-formamide form) in 56-% yields, and rate constants for the ring-opening reactions of 16a, b, d-g (X=ClO₄) and 16 (X=Br) leading to a-g were determined in H₂O at pH .84 and ionic strength 0.50 at 25°. Cyclization of a with NaH in AcNMe₂ at room temperature or with boiling 1N aqueous NaOH produced 21a in 84% or 72% yield, respectively.In solution, the trans-formamides seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in D₂O or Me₂SO-d₆ at 25° or in H₂O at pH .84 and ionic strength 0.50 at 25° was kinetically confirmed in the case of a, and the mechanism of the rearrangement of 16 to 21 through is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH₄ in MeOH at room temperature, 16a (X=I) furnished the , -dihydro derivative 28 (84% yield), which slowly decomposed in H₂O at 60° to give a in 49% yield.The , -dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl--formamidoimidazole-4-carboxamidines () through an alternative synthetic route : Alkylations of with alkyl halides in HCONMe₂ in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of a, the 2-deuterated species 26 was also synthesized from 24 via 25 and 27.

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The activities of tobramycin derivatives acetylated and ethylated on the 6'-N, 2'-N and 3-N positions were examined. The MICs of these derivatives against tobramycin sensitive strains indicated that 2'-N-ethylated and 6'-N-ethylated derivatives have a fairly good activity, and confirmed that the 3-N position is the most important one for antibiotic activity since 3-N derivatives were less active. The MICs of these derivatives against tobramycin resistant strains, and their inactivation by tobramycin modifying enzymes were examined. These results showed that 2'-N or 6'-N ethylation protects the drug against inactivation by AAC(2') or AAC(6'), respectively, and 2'-N-ethyltobramycin and 6'-N-ethyltobramycin were active against strains containing these modifying enzymes. On the other hand, 3-N ethylation protects the drug against inactivation by AAC(3) but 3-N-ethyl tobramycin does not inhibit strains containing this enzyme.

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Eight new sterols, , -epidioxy-(, 24R)-23-methylergosta-6, -dien-3β-ol (1), 3β, , -trihydroxy-(, 24R)-23-methylergosta-, -dien-6-one (2), 3β, , -trihydroxy-(24S)-ergost--en-6-one (3), 3β, , , 14α-tetrahydroxy-(, 24R)-ergosta-, -dien-6-one (4), (, 24R)-ergosta-, -diene-3β, , 6α, -tetrol (), , -epidioxy-3β-hydroxy-(, 24R)-ergosta-, -dien-6-one (6), , -epidioxy-3β-hydroxy-(24S)-ergost--en-6-one () and , 6α-epoxy-(, 24R)-ergosta-, -diene-3β, , 14α-triol (), have been isolated from five edible mushrooms, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones (-23), of which two (16 and 17) are reported for the first time from a fungal source. The structures of these new compounds were elucidated on the basis of their spectral data.

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One method currently being considered for the disposal of high level radio-active waste is burial in the seabed. When a hot object is buried in soil, the temperature of the soil adjacent to the object is raised and there is transient heat flow away from the object. The rise in the temperature of the soil causes excess pore pressures to be generated and transient pore water diffusion also takes place. A finite element formulation of the coupled heat flow and consolidation problem is presented. The computer implementation of this formulation is found to compare favourably with analytical solutions based on the same physical principles.

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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

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

,355 deaths in women during the median follow-up of 18. years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0. (95% confidence interval [CI], 0.76–0.90; P for trend < 0.0001) for vitamin , 0.85 (95% CI, 0.78–0.93; P for trend < 0.0001) for vitamin , 0. (95% CI, 0.–0.96; P for trend = 0.0006) for β-carotene, and 0.90 (95% CI, 0.82–0.98; P for trend = 0.0002) 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 , 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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(³H) Tobramycin was used as a probe to determine the relationship between the structure of aminoglycoside antibiotics and their ability to remove this drug from its higher affinity binding site on the ribosome. The dissacharide moieties (neamine, tobramine, gentamine) appeared to have a common binding site, whereas the kanosamine, garosamine and ribose moieties determined the specificity of this binding. Amikacin and butikacin behaved in an anomalous manner in spite of their close structural relationship to tobramycin.

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Stereoselective synthesis of , - and , Z-β-ionylideneacetaldehydes was accomplished from the β-ionone tricarbonyl iron complex, and the latter was converted to Z-retinoic acid.

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Six new sterols, , 6α;, -diepoxy-(, 24R)-ergost--ene-3β, -diol (1), , 6α;, -diepoxy-(, 24R)-ergost--ene-3β, -diol (2), , 6α-epoxy-(, 24R)-ergosta-, -diene-3β, -diol (3), (, 24R)-23-methylergosta-, -diene-3β, , 6β-triol (4), (, 24R)-23-methulergosta-, -diene-3β, , 6β, -tetrol () and (24S)-ergost--ene-3β, , 6β, -tetrol (6), have been isolated from seven mushrooms, Amanita pantherina, Amantia virgineoides, Lactarius piperatus, Lyophyllum shimeji, Tricholoma portentosum, Hypsizigus marmoreus and Lentinula edodes together with eighteen known ones (-24). The structures of these new compounds were elucidated on the basis of their spectral data.

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 The stability of

‒tetrahydrocannabinol acetate (‒THC‒OAc) and ‒tetrahydrocannabinol acetate (‒THC‒OAc) in -liquid during storage was investigated. ‒THC‒OAc liquids in cartridges were stored at 80℃ or 30℃ for 28 days. The relative concentrations of cannabinoids in the liquids were measured by gas chromatography with flame ionization detection. ‒THC‒OAc decreased during storage at either temperature. ‒THC, a minor impurity, also decreased. ‒THC‒OAc liquid in a cartridge was stored at 80℃ for 57 days. The concentration of ‒THC‒OAc and ‒THC, a minor impurity, did not change during that time. Cannabinol acetate increased in all liquids, and unknown products were also detected by gas chromatography/mass spectrometry (GC/MS). The ‒THC‒OAc and ‒THC‒OAc liquids were subjected to GC/MS to detect representative diluents, glycerol, propylene glycol, and polyethylene glycol 400, but none of these were detected.

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A minute alga Tetraselmis tetrathele is one of the food organisms which have been intoroduced into Japan recently. T. tetrathele was well evaluated already as a substitute for Chlorella because of the high food value for a rotifer Brachionus plicatilis and its eurythermal characteristic beside the tolerance to high temperature. But, the dietary value of the rotifer cultured with T. tetrathele remains unknown.
Tje doetary value of rotifers cultured with T. Tetrathele (TR) or both T. tetrathele and Chlorella sp. (TCR) was compared with those cultured with Chlorella (CR) by feeding these various rotifers to larval red seabream for 17 days. The rotifers enriched by Chlorella (12-24 hours) after culturing with T. tetrathele (TR-) was also given to the larvae. The survival rate and the total length of fish fed TR was better than those receiving CR (75.6 and .% vs. 65.1 and 75.6% in survival rate, . and .1 mm vs. 6. and 6. mm in average T. L.), although there were no significant dif-ferences in body weight. Furthermore, the survival rate and the growth of fish fed TCR or TR- were superior to the former, i. ., 68.0-80.1% and .-.mm in TCR, 74.4-.1% and .-.1mm in TR-. There were no differences in proximate composition of the rotifers with various feeds and treatment. The difference in survival rate and growth among the larvae with different feeds might be due to the difference in the conten of ω3 HUFA. Thepercentage of ω3 HUFA in the lipids of TR, TCR, TR-, and CR were 12.4%, 20.%, 20.4-25.4%, and 23.%, respectively. The amount of ω3 HUFA in the rotifers cultured with T. tetrathele was not enough, but might be the minimum (0.3% in rotifer). The influence of 18:3ω3 included in the rotifer at high per-centage (.4%) should be studied in future works.

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