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%; 79,5±2,%; 83,5±2,%; ,6±2,%; 80,6±4,4%; for Generic1 - 0; 49,±,%; 88, ±2,%; 90,4±,7%; 88, 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,%; 66,7±,2%; 76,4±7,4%; ,±5,%; 86,0±,7%; 84,6±,%: for Generic - 80,±,6%; 83,5±1,%; 83, ±,2%; 83,±2,7%; ,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,5±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, 5±

,0%; 62,±2,0%; 80,0±,1%; 85,4±2,%; ,±,4%; 80,±,5%; for Generic1 - 0; 67,0±7,%; 89,7±2,%; 91, ±4,%; 89,1±1,6%; 88,±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±5,6%; 75,1±7,%; ,0±6,0%; 88,4±,2%; 88, 6±1,%; 87,±1,0%; for Generic4 - 85,5±0,5%; 85,6±0,5%; 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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The nucleus ¹²C was bombarded by .1–MeV

3He

particles to study elastic and inelastic scattering and the (

3He

, α) reaction. Angular distributions were measured for the elastic scattering, for the inelastic scattering to levels at 4.4, 7.6 and

9

.6 MeV in ¹²C, and for the (

3He

, α) reaction to levels at 0.0, 2.0, 4.

3

(4.7) and 6.4 MeV in ¹¹C. The optical potential parameters were searched for to fit the

3He

elastic scattering angular distribution. The deformation parameters β₂ and

β₃

for ¹²C were determined from DWBA analysis. The angular distributions of α particles were compared with DWBA calculations and calculations including the two-step process via inelastic channel.

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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,,4,5,6,7,,-

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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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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[Purpose] This study investigated the therapeutic effects of augmented reality (AR)-based EMG-triggered functional electric stimulation (FES) on stroke patients receiving rehabilitation. [Methods] Ten subjects who were in the chronic phase following stroke were divided into two groups for: ankle dorsiflexion with AR-based EMG-triggered FES (Experimental group, n=5), and EMG-triggered FES alone (Control group, n=5). Experimental subjects received ankle dorsiflexion with AR-based EMG-triggered FES for 20 minutes per day, 5 times per week over a 4 week period. Muscle activation, ankle range of motion and muscle strength were measured to identify the effect of the AR training environment with EMG-triggered FES. [Results] The muscle activation of the medial and lateral gastrocnemius (GCM), as measured by EMG, the improvement was increased significantly after the intervention compared to before within the experimental groups of the tibialis anterior(TA), and the improvement was significantly greater in the experimental group than in the control group. Muscle strength of the tibialis anterior (TA) and GCM in dorsiflexion and plantarflexion were significantly greater post-intervention in the experimental group. [Conclusion] The results of this study provide evidence in support of incorporating an AR environment into ankle dorsiflexion training with FES for the improvement of muscle activity, and strength of chronic phase stroke patients.

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The effects of T- (2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,-dihydro--methoxy-1H-pyrrolo[,4-b]quinolin-1-one hemifumarate), a new quinoline derivative, on acetylcholinesterase (AChE) activity and acetylcholine (ACh) release were compared with those of the well-known cholinesterase inhibitors tacrine and 2020. T-, tacrine and 2020 all concentration-dependently inhibited AChE in rat brain homogenate (IC_50s = 109.4, 84.2 and 11. nM, respectively). In addition, although tacrine strongly inhibited butyrylcholinesterase (BuChE), T- and 2020 showed only weak activity on BuChE in human plasma. In ex vivo experiments, intraperitoneal administration of T- at a dose of 30 mg/kg inhibited AChE activity in the hippocampus, frontal cortex and parietal cortex of rats. The effect of T- on the extracellular ACh concentration in rat brain was measured using in vivo microdialysis. T- at doses of 10 and 30 mg/kg, i.p. increased the extracellular ACh concentration in the hippocampus and striatum in a dose-dependent manner. These findings suggest that T- activates the central cholinergic system by selectively inhibiting AChE activity, while weakly affecting peripheral BuChE activity, and that T- increases the extracellular ACh concentration in the brain, which is followed by inhibited AChE activity.

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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-,5α,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-,5α,6β-triol (4), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , 5 and 6 did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C-5 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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To determine l-ephedrine () and d-pseudoephedrine (PE) concentrations in human plasma simultaneously, we used a selected-ion monitoring method with gas chromatography-mass spectrometry (GC-MS) using deuterium-labeled and PE as internal standards. The and PE in human plasma were extracted with hexane-ethylacetate (/1) under alkaline conditions and were easily converted into their heptafluorobutyryl derivatives by treating with heptafluorobutyrylimidazole. The calibration curves of and PE showed a good linearity in the range from 0. to . ng/ml for , and from 0.41 to 41.0 ng/ml for PE, respectively. the limit of detection was 0. ng/ml for and 0.41 ng/ml for PE in human plasma, respectively.

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Six full-length cDNAs encoding pig cytochrome P450 (CYP) enzymes, CYP1A1, CYP2A19, CYP2B, CYP2C33v4, CYP2C49, and CYP21, were isolated and sequenced. The cDNA sequences of pig CYP1A1, CYP2A19, CYP2B, CYP2C49, and CYP21 showed high similarity to human CYP1A1 (85.4%), CYP2A13 (88.6%), CYP2B6 (.1%), CYP2C18 (85.%), and (.5%), 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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N-(2-フルオレニル) -マレイミド (I), N-1-(4-アセトキシナフチル) -マレイミド (II), N-2-(-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 (), 頻度係数 (A) は=26.4kcal/mol (I), 23.kcal/mol (II), .kcal/mol (III), A=.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, 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, =1., II (M₁) -V (M₂) 系で, r₁=0.17, , Q₁=0.51, =1.37, III (M₁) -V (M₂) 系で, r₁=0.068, r₂=1.34, Q₁=0.87, =1.90となった.

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Solanapyrones were polyketide natural products isolated by Oikawa and Ichihara et al. from Altenzaria solani, a causal fungus of early blight disease to tomato and potato. These unique compounds possess decaline framework with pyrone nucleus and exhibit inhibitory activity against germination of hypocotyl and root of lettuce. Total synthesis of solanapyrone , one of the solanapyrones having trans-decalin with hydroxymethyl pyrone ring, has been accomplished by domino Michael reaction and by hydroxymethylation of pyrone ring as key transformations. Decaline framework having requisite functionalities for solanapyrone synthesis was obtained by domino Michael reaction between methyl crotonate and kinetic enolate of optically active acetylcyclohexene derivative prepared by Lipase catalyzed kinetic resolution. Treatment with base provided trans-decalone in which C-2 methyl and C-10 hydrogen were β-syn in each other. After removal of alkoxy group at C- by Barton's radical protocol, carbonyl group at C-4 was reduced with L-selectride to give β-axial alcohol which was selectively dehydrated into double bond at C- via pyrolysis of xanthate. Base catalyzed isomerization of the α-axial ester at C-1 was accomplished by t-BuOK in DMSO. The ester was then transformed into formyl group. β-Hydroxypyrone unit at C-1 was installed by TiCl_4 promoted condensation of bisTMS enol ether of methyl acetoacetate with the aldehyde followed by Jones oxidation and subsequent DBU catalyzed cyclization. Phenylthiomethyl group was introduced to a position of pyrone carbonyl group by the reaction of paraformaldehyde and thiophenol in the presence of piperidine. After protection of the hydroxy group by methyl ether formation, phenylthio group was oxidized into phenylsulfinyl group. Treatment of the sulfoxide with trifluoroacetic anhydride led to O-acylation of sulfoxide followed by substitution with trifluoroacetoxy anion and completed the total synthesis of solanapyrone .

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