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 .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±,0%; 62,±4,0%; 79,5±2,9%; ,5±2,9%; 81,6±2,9%; 80,6±4,4%; for Generic - 0; 49,±9,9%; 88, ±2,%; 90,4±,%; 88, 2±2,2%; ,±2,0%; 85,9±,%; for Generic2 - 0; 30,6±6,%; 66,±,2%; 76,4±,4%; ,±5,%; ,0±,%; 84,6±,%: for Generic - 80,±,6%; ,5±,9%; , ±,2%; ,±2,%; 81,9±2,%; ,±2,0%; ,0±2,4%; for Generic4 - ,5±,%; 84,4±0,%; 84,2±,2%; , 9±0,9%; ,9±0,9%; ,9±0,9%; ,±,%, 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, 5±,0%; 62,±2,0%; 80,0±,%; 85,4±2,9%; ,±,4%; 80,9±,5%; for Generic - 0; 67,0±,%; 89,±2,%; 91, 9±4,%; 89,±,6%; 88,±,4%; ,±,2%; for Generic2 - 0; 42,2±5,6%; 75,±,%; 81,0±6,0%; 88,4±,2%; 88, 6±,%; ,9±,0%; for Generic4 - 85,5±0,5%; 85,6±0,5%; 84,±0,9%; ,±,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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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the ^116mIn activity. Directional correlations are also measured for 818–1293 and 1097–1293 keV cascades. The M-2 mixing ratio δ, and the 0-2 mixing ratio μ_k are obtained for 818. keV +→2₁⁺ transition to be δ=−+0.26, and μ_k≤6.×10⁻⁴ respectively. The 2 branching ratio (2; +→0_g⁺): (2; +→2₁⁺): (2; +→0₁⁺) is determined to be 0.0158:.0:5..

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The mechanism of wave-induced instability in a permeable seabed have been studied for more than two decades. The distinction between shear failure and liquefaction, however, has not been clearly defined. This paper presents a fundamental study on the differences in two failure modes for a fully saturated seabed of both finite and infinite thickness. The wave-induced effective stresses and pore pressure, obtained from an analytical solution of Biot's pore-elastic consolidation theory, were employed to examine the failure modes under a two-dimensional plane strain condition. A case study is presented to examine the failure modes with respect to several parameters, such as excess pore pressure, seepage flow, seepage force, failure areas and stress path in the seabed. The conclusions obtained from this study were as follows ; () the thickness of a permeable seabed affects the pore pressure and effective stress response to ocean waves and the failure mode of the seabed, (2) either a liquefaction or shear failure, or both, occur in the seabed, even in the saturated seabed, () the Mohr-Coulomb's failure criterion, when combined with elastic stresses, can not be employed to estimate the liquefaction failure in the seabed, (4) the liquefaction can be evaluated by a criterion in terms of the excess pore pressure, (5) The liquefied zone in the seabed is significantly different from the shear failure zone. The shape beneath the seabed surface for the former is almost identical to the contour where the upward seepage flow is concentrated.

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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), 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,6β-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,6β-triol (4), -dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT- cells were increased .0-fold by 10 μM and 2.4-fold by 10 μM 4. However, 2, , 5 and 6 did not induce MCT- cell ALP activity at 0.—10 μM. These results suggested that the OH groups at C-5 and/or C-6 of and 4 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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In the 1993 Kushiro-oki Earthquake of Richter magnitude ., simultaneous recording of earthquake motions was successfully made at the ground surface and at a depth of 77 meters in a dense saturated sand deposit. The peak horizontal acceleration was 0.47 g on the ground surface and 0.21 g at a depth of 77 meters. The acceleration record at the ground surface showed a distinctive ground response, which consisted of a cyclic motion having a period of about .5 seconds overlain by a spike at each peak of the motion. In order to study the mechanism of this peculiar ground response, effective stress analysis was conducted on the dense saturated sand deposit. The model used for this study was a strain space multiple mechanism model, which takes into account the effect of principal stress axis rotation. The recorded earthquake motion at a depth of 77 meters was used as the input earthquake motion for the analysis. Sampling after in-situ freezing was done in order to evaluate the properties of the sand. The results of the analysis indicated that the observed ground response was due to the effect of dilatancy of sand, which plays a significant role in the response of the dense saturated sand deposits during strong earthquake motions.

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  The distribution of sarcophytol-A in the Sarcophyton genus was investigated in seven samples belonging to S. glaucum ( samples), S. infundibulifurme (2 samples), S. crassocaule ( sample) and S. trocheliophorum ( sample) that were collected on Ishigaki Island in Okinawa Prefecture. Sarcophytol-A was present in one sample each of S. glaucum and S. infundibulifurme. This study indicates that the composition of cembranoids in the Sarcophyton genus is not related with the respective species, but with the individual samples collected.

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A sample of [

3H

] tobrarnycin (5, 000 Ci/Mole) has been synthetized and incubated with
the bacterial ribosome and its subunits. The results obtained show that this antibiotic has
two types of binding sites. The primary one is probably responsible for the inhibition of
protein synthesis whereas the secondary one is probably related to the misreading and reading
tiirough of the messenger RNA.

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In this paper, centrifuge shaking table tests were conducted in order to understand the performance of seawalls during a seismic event. The model tests showed that the displacement of the caisson was much affected by the seaward shear deformation of the sand seabed beneath it during shaking. It was also confirmed that an armored embankment played an important role in the displacement of the caisson during shaking. Based on these test results, a two-dimensional DEM-FEM coupled analysis method was newly developed to numerically predict the deformation of seawalls covered with armored embankments during earthquakes. The movements of the armor units were calculated by DE analysis and deformations of the caisson, rubble mound, sand seabed and backfill were calculated by FE analysis considering the non-linearity of the soil materials based on the effective stress. Dynamic interaction was taken into account by delivering the nodal displacements of the finite elements or the nodal forces converted from the contact forces through the imaginary distinct elements defined at the boundaries between the DE and FE domain. The applicability of this method to the prediction of the deformation of seawalls was verified through numerical simulations of the centrifuge model test.

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Seismic records obtained from a seismometer array located in downtown Tokyo Japan for about ten years were inversely analyzed to estimate the dynamic soil parameters. Due to the illposed nature of the problem, the simple and often used "least square method" does not properly estimate the parameters. The Extended Bayesian Method combined with the Akaike Bayesian Information Criterion was introduced to overcome this difficulty. The results obtained were compared with dynamic triaxial test results obtained at the time of the seismometer installation. The shear moduli agree quite well with the estimated results, however the damping ratios estimated are slightly higher than the ones obtained in the laboratory.

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This paper concerns the stability against overturning of the caissons on rubble mound subjected to wave loading. A theoretical discussion is first made of the stability of a leaning caisson during wave loading, as a single degree-of-freedom system. The expression for the lower bound of driving moments sufficient to overturn a given caisson is derived. A review is then made of the damages induced to a composite breakwater, which consisted of two adjoining Stretches and C with slightly different sizes of caissons. Attention is called for the observation that most of the caissons in Stretch were overturned, whereas no caissons in Stretch C were brought into overturning. This fact is examined in detail in the light of the theory of overturning, making it possible to estimate the destructive wave heights that are compatible with the observed patterns of damage in Stretches and C of the composite breakwater.

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Stress wave theory is applied to open-ended pipe piles to clarify the effects of soil plug on the behaviour of piles during driving and static loading. Measured field data and various numerical models are reviewed ; methods are presented to calculate wave propagation in both the pile and the soil plug ; modelling is presented which takes into account the interaction between the soil plug and the pile ; also presented is simplified method to estimate the loadsettlement relation of the pipe pile in static loading. By correlating observed and calculated values in two analytical cases, the authors demonstrate that incorporation of the soil plug (modelled as a series of masses and springs) is required to correctly predict pile behaviour during driving and static loading.

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N-(2-フルオレニル) -マレイミド (I), N--(4-アセトキシナフチル) -マレイミド (II), N-2-(9-アセトキシフルオレニル) -マレイミド (III) の単独重合, 共重合をアゾビスイソブチロニトリル (IV) を開始剤としてテトラヒドロフラン中, 60℃で行った. 単独重合の初速度 (R_p) は, R_p=k [I] ^2.11 [IV] ^0.64, R_p=k [II] ^2.26 [IV] ^0.72, R_p=k [III]

1.76

[IV] ^0.52となった. kは速度定数である. 全重合の活性化エネルギー (

E

), 頻度係数 (A) は

E

=26.4kcal/mol (I), 23.

3

kcal/mol (II),

22

.

8

kcal/mol (III), A=

3

.4×10¹⁵ (I), 2.

7

×10¹¹ (II),

1

.5×10¹¹ (III) となった. またN置換マレイミドとメタクリル酸メチル (V) との共重合におけるモノマー反応性比, Q,

e

値を次のように決定した.
I (

M₁

) -V (M₂) 系で,

r₁

=0.24, r₂=0.93,

Q₁

=0.43,

e₁

=

1

.

82

, II (

M₁

) -V (M₂) 系で,

r₁

=0.17,

r₂2.29

,

Q₁

=0.51,

e₁

=

1

.37, III (

M₁

) -V (M₂) 系で,

r₁

=0.068, r₂=

1

.34,

Q₁

=0.

87

,

e₁

=

1

.90となった.

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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 (88.6%), followed by streptomycin (80.%) and ampicillin (64.%). Resistance to cefazolin, cefoperazone, cefepime and amikacin was very low. Of the 176

E

. coli strains, forty (.%) isolates from 30 farms showed resistance to fluoroquinolones (FQ). All the FQ-resistant strains possessed double mutations at codons and in the gyrA gene, and a single mutation mostly at codon 80 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.

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The phase diagrams of the Ni-Mo- and Ni-W- ternary systems in the region of less than 50mol% were constructed by thermodynamic calculation, based on the data obtained by thermodynamic measurement of the related materials. We found three ternary eutectic points and three or two ternary peritecto-eutectic points as follows:
:L (1365K, 71.5mol%Ni-6.0mol%Mo-.5mol%)=(Ni)++
:L (1355K, 62.5mol%Ni-2.5mol%Mo-30.5mol%)=++
:L (1445K, 42.0mol%Ni-30.6mol%Mo-10.mol%)=(Ni)+NiMo+
:L (1812K, 34.9mol%Ni-42.mol%Mo-.mol%)+MoB=+
P₂:L (1633K, 42.mol%Ni-40.4mol%Mo-17.mol%)+Mo=+
:L (1812K, 53.5mol%Ni-33.mol%Mo-12.mol%)+Mo=NiMo+
:L (1622K, 51.0mol%Ni-31.6mol%W-17.4mol%)=(Ni)+W+
:L (1260K, 71.0mol%Ni-.0mol%W-.0mol%)=(Ni)++
:L (1291K, 65.4mol%Ni-4.mol%W-29.mol%)=++
:L (2115K, 23.mol%Ni-43.mol%W-33.mol%)+WB=+
P₂:L (1657K, 48.9mol%Ni-33.mol%W-18.0mol%)+=W+
The calculated phase diagrams are expected to be useful for the development of new Ni-based heat-, corrosion- or wear-resistance alloys.

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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 , 4, 6-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, 4-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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ドコサヘキサエン酸エチル (-DHA) の大量精製方法の確立を目的とし, 固定化Rhizomucor mieheiリパーゼでマグロ油由来のエチルエステル (-DHA 55; -DHA含量, 55mol%) をラウリルアルコール (LauOH) でアルコリシスした。固定化リパーゼを充填したカラム (.0g; ×63mm) に-DHA/LauOH ( : , mol/mol) の混液を30℃, 10mL/hの流速で負荷した。その結果, エステル交換率は58%に達し, エチルエステル画分の-DHA含量はmol%まで上昇した。この固定化酵素リアクターを150日間連続運転すると, エステル交換率は48%まで低下したものの, -DHA含量はほとんど低下せず85mol%まで上昇していた。カラムから溶出した反応液中のエチルエステルは薄膜蒸留により収率よく回収できたが (%), この画分には2.4wt%のLauOHと6.wt%のラウリルエステルが混在していた。このうち, ラウリルエステルは尿素包括により完全除去することができた。一連の精製操作により, -DHA55に含まれていた-DHAの52%が回収でき, -DHA含量を88wt%まで高めることができた。

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The ability of Climacodon septentrionalis to immobilize and kill a mycophagous nematode (Aphelenchoides sp.) in vitro is described for the first time. Two isolates produced droplets (20–45 μm in diameter) that formed at the apices of tall, stalked, and branching secretory cells (700–

,500 μm tall). On 2% modified malt extract agar, nematodes became enveloped in the droplets, which restricted their ability to move and resulted in complete immobilization and death within several hours of contact. The rate of decomposition of the nematodes varied considerably, with most individuals persisting for weeks whereas others were degraded within several days and appeared to be colonized by dense hyphal growth. This study provides the first documentation of a non-agaricoid fungus producing secretory cells that are able to immobilize nematodes.

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We previously reported human papillomavirus type 52 (HPV52) as the most prevalent high-risk genotype in non-cancer individuals in Vietnam. This study aimed to evaluate HPV genotypes and HPV16

6 and (6/) gene variations in Vietnamese patients with genital cancers. Biopsy samples were collected from 124 Vietnamese patients with genital cancers (20 with vaginal, 50 with vulvar, and 54 with penile cancer). The HPV-DNA was amplified and genotyped, and HPV16 6/ genes were compared with those previously reported for women with normal cervical cytology (N = 23). HPV-DNA was detected in 80.6% (100/124) of the cancer patients (80.0% of vaginal, .0% of vulvar, and 79.6% of penile), with HPV16/18 in .0% (/100) and HPV52 in .0% (/100) of the HPV-positive samples. The HPV-DNA prevalence and HPV genotype distribution did not significantly differ among the genital cancer patients (both P = 0.95). Significantly fewer instances of the HPV16 A4 sublineage (34.% vs. .6%, P < 0.0001) and HPV16 29S (36.4% vs. .0%, P = 0.0002) occurred in the cancer patients than in the women with normal cytology. Our results indicate that HPV16/18 accounts for more than 85% of genital cancers in Vietnam, and the HPV16 sublineage A4 containing 29S may be less oncogenic.

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