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±.05) to pH 7. (7.±.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.±.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±

,7%; 41,4±,%; 62,±4,%; 79,±2,9%; 83,±2,9%; ,6±2,9%; 80,6±4,4%; for Generic1 - ; 49,±9,9%; , ±2,%; 90,4±,7%; , 2±2,2%; 87,±2,%; 85,9±1,1%; for Generic2 - ; 30,6±6,%; 66,7±,2%; 76,4±7,4%; ,±,%; 86,±,7%; 84,6±,%: for Generic - 80,±,6%; 83,±1,9%; 83, ±,2%; 83,±2,7%; ,9±2,1%; ,1±2,%; ,±2,4%; for Generic4 - ,±1,7%; 84,4±,%; 84,2±1,2%; , 9±,9%; ,9±,9%; ,9±,9%; ,±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±

,6%; 40, ±,%; 62,±2,%; 80,±,1%; 85,4±2,9%; ,±,4%; 80,9±,%; for Generic1 - ; 67,±7,%; 89,7±2,%; 91, 9±4,%; 89,1±1,6%; ,±1,4%; 87,±1,2%; for Generic2 - ; 42,2±,6%; 75,1±7,%; ,±6,%; ,4±,2%; , 6±1,%; 87,9±1,%; for Generic4 - 85,±,%; 85,6±,%; 84,7±,9%; ,7±,%; 84,4±,%; 84,4±,%; 84,±,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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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=1 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 : (1) 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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Six full-length cDNAs encoding pig cytochrome P450 (CYP) enzymes, CYP1A1, CYP2A19, CYP2, CYP2C33v4, CYP2C49, and CYP21, were isolated and sequenced. The cDNA sequences of pig CYP1A1, CYP2A19, CYP2, CYP2C49, and CYP21 showed high similarity to human CYP1A1 (85.4%), CYP2A13 (.6%), (.1%), CYP2C18 (85.%), and (.%), respectively, and pig CYP2C33v4 cDNA showed high similarity to rat CYP2C23 (79.2%). Reverse transcription-polymerase chain reaction (RT-PCR) assays revealed hepatic gene expression of all these pig CYP enzymes: the order of expression was CYP2C33v4 and > CYP2C49 > CYP1A1 and CYP2A19 > . In the kidney, the CYP2C33v4 gene was expressed at the same level as in the liver, but the CYP1A1, CYP2A19, and genes were expressed at lower levels than in the liver. Little renal gene expression of CYP2C49 and CYP21 was observed. We revealed for the first time the full-length cDNA sequences encoding pig CYP1A1 and five CYP enzymes belonging to the CYP2 gene family, thus making it possible to examine the gene expression levels of these CYP enzymes in pig tissues by RT-PCR.

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長期的に見ると、景気のトレンドが低下し、在庫投資や設備投資の変動が小さくなっている。その背景には、経済のサービス化、グローバル化、DX、研究開発投資の拡大などの経済構造の変化がある。こうした中で、第 16 循環の山（2018 年 10 月）付近においては、景気動向指数（一致指数）と実質GDPの動きに乖離が見られたが、その要因としては、外需の減少ペースが景気を一気に冷え込ませるような急激なものではなかったことが大きい。加えて、労働市場では、人口減少下で女性や高齢者を中心に労働市場に参入する人が増え、雇用所得環境を下支えしていた。コロナショック後は、賃上げのモメンタムが強まっている。今後、労働市場の構造変化がどのように進むのか、それが景気循環にどのような影響を与えるのか、注視していく必要がある。 こうした景気循環の特徴の変化やその背景にある経済構造の変化を踏まえると、景気循環を適切に捉えるためには、第一に、景気循環の転換点を敏感に捉える必要があることに変わりはないが、一方で、第二に、生産に過度に重点を置かず、より幅広い指標を観察すること、第三に、経済の全体的な動向を捉えるという観点から、実質GDPの動向にも留意すること、が必要となろう。

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The applicability of a method for predicting 'bearing capacity increase'in reinforced sandy ground was examined using tests performed under various test conditions. It was found that the present method predicted, with reasonable accuracy, the bearing capacity increase in sandy ground, reinforced with stiff reinforcement. This method may not be applicable for sandy ground reinforced with extensible reinforcement due to the unsuccessful formation of a semirigid zone under the footing. An investigation into the settlement of a footing on reinforced sandy ground, at ultimate footing load condition, suggested that the settlement of footing for reaching peak footing load may be correlated to the 'deep-footing'and the 'wide-slab'mechanisms. That is, the ultimate settlement ratio between reinforced and unreinforced model sandy ground, SR_f, may be linearly correlated to 'BCR_D'and 'BCR_s', which represent 'deep-footing' and 'wide-slab'effects, respectively, on the ultimate bearing capacity increase in reinforced sandy ground.

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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-1. Sixteen phosphate buffered saline (PBS), boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-1 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-7,-diene-,,6β-triol (1). 1 induced ALP activities of MCT-1 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-1 cells by 1, ergosterol (2), ergocalciferol (), cholesta-,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , and 6 did not induce MCT-1 cell ALP activity at .1—10 μM. These results suggested that the OH groups at C- and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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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 (.g; ×63mm) に-DHA/LauOH (1 : 7, 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87mol%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wt%まで高めることができた。

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The relationship between withers height and hip height of 378 purebred Holstein-Friesian cows in Japan aged over 4, which have good dairy conformation and heigh milk production, is investigated by the Writer from biometric standpoint. And the results are as follows:
1. Biometric constants.
Withers height. (c.m.) Hip height. (c.m.)
M……135.93±, 167 137.33±.184
σ……4.±.118 .29±.130
V…….55±.087 .85±.095
Q…….17±.228 .45±.250
Mi……135.40±.210 136.90±.230
Mo……137.00±.205 139.00±.225
S……-.±.042 -.32±.042
2. The frequency curve of withers height is Y=378/4.√2π -1/2(χ-135.93/4.)2×2, and that of hip height Y=378/.29√2π -1/2(χ-137.33/.20)×2.
.The correlation coefficient between there two characters is +.96±.003.
4.The regression equations are (denoting withers height and hip height by X and Y, respectively).
X=.Y+16.45……(1)
Y=1.05X-.40……(2)

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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,,4,,6,7,,9-¹³C₉, ^15/N]phenylalanine was converted to ()-[1,2,,4,,6,7,,9-¹³C₉]cinnamate and ()-[1,2,,4,,6,7,,9-¹³C₉]methyl cinnamate. Similarly, 100% selective ¹³C incorporation was observed when ()-[1,2,,4,,6,7,,9-¹³C₉]cinnamate was converted to ()-[1,2,,4,,6,7,,9-¹³C₉]methyl cinnamate. In contrast, the ²H incorporation selectivities were .1% and .4% when L-[2,,4,,6,7,7,-

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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Objective: This study was conducted to determine whether to perform endovascular intervention or bypass surgery as a treatment option for critical limb ischemia (CLI) with lesions in the popliteal artery or below.Subjects and Methods: A total of 150 patients (164 limbs) with CLI underwent endovascular intervention or bypass surgery for lesions in the popliteal artery or below at our department between May 1995 and June 2011. Therapeutic outcomes were examined by surgical technique. An indication for endovascular intervention was established with the combination of (1) poor general condition, and (2) a stenotic or occlusive lesion ≤ cm.Results: The bypass group (group ) comprised 119 patients (99 males, 20 females) with 131 affected limbs at 46 to 89 years of age (mean: 70 years). The endovascular intervention group (group ) comprised 31 patients (25 males, 6 females) with 33 affected limbs at 47 to 89 years of age (mean: 72 years). There was no significant difference in patient demography between the two groups. Regarding preoperative complications, hypertension was observed in 54% and 61% of the subjects in groups and , respectively, diabetes in 36% and 55%, renal dysfunction in 29% and 58%, ischemic heart disease in 27% and 32%, and cerebrovascular disorder in 18% and 23%; renal dysfunction accounted for a significantly higher percentage in group . As for early postoperative complications, subjects in group experienced wound infections (6 patients), hemorrhage (2), thrombosis (2), pneumonia (1), and another complication (1), and those in group experienced wound infections (1) and another complication (1). The hospital mortality rate was .% (1 patient) for group and % for group . The -year cumulative primary patency rate was 72% for group and 54% for group ; the rate was significantly higher for group . The -year secondary patency rate was % for group and 60% for group . The -year limb salvage rate was 86% for group and % for group ; there was no significant difference between the two groups. The -year survival rate was 57% for group and 42% for group ; the survival rate was significantly lower for group .Conclusion: For the study population of CLI patients with lesions in the popliteal artery or below, the patency rate was higher for the bypass group than for the endovascular intervention group, whereas there was no difference in the limb salvage rate. Based on the findings in prognosis for survival, the indication for endovascular intervention at our department is believed to be appropriate. (*English translation of Jpn J Vasc Surg 2013; : 715-718)

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