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 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±3,0%; 62,8±4,0%; 79,

±2,%; 83,±2,%; 81,6±2,%; ,6±4,4%; for Generic1 - 0; 49,3±,%; 88,8 ±2,8%; 90,4±3,7%; 88, 2±2,2%; 87,3±2,0%; ,±1,1%; for Generic2 - 0; 30,6±6,3%; 66,7±8,2%; 76,4±7,4%; 82,8±,3%; ,0±3,7%; ,6±3,3%: for Generic3 - ,8±3,6%; 83,±1,%; 83, 8±3,2%; 83,3±2,7%; 81,±2,1%; 82,1±2,0%; 82,0±2,4%; for Generic4 - 82,±1,7%; ,4±0,8%; ,2±1,2%; 82, ±0,%; 82,±0,%; 82,±0,%; 82,8±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,

±3,0%; 62,8±2,0%; ,0±3,1%; ,4±2,%; 82,8±3,4%; ,±3,%; for Generic1 - 0; 67,0±7,8%; 89,7±2,3%; 91, ±4,3%; 89,1±1,6%; 88,3±1,4%; 87,8±1,2%; for Generic2 - 0; 42,2±,6%; 75,1±7,3%; 81,0±6,0%; 88,4±3,2%; 88, 6±1,3%; 87,±1,0%; for Generic4 - ,±0,%; ,6±0,%; ,7±0,%; 82,7±3,0%; ,4±0,3%; ,4±0,3%; ,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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To develop truly autonomous and intelligent mobile robots, the developmental approach is indispensable. Considering the development of human beings, internal rewards which are related to the instinctive desire, motivation, curiosity, novelty, etc., are important factors contributing to the development. For the robots, there are several studies in which curiosity and novelty are used to promote the progress of learning. In this paper we propose an internal reward called "appetitive reword" and a function to control it, for the robots which have to acquire an action policy for a mission to "survive and perform a instructed task effectively". The "appetitive reword" is inspired by "appetite" of human beings, which is known to be well regulated by a mechanism between the digestive tract and the brain. By using an example of a security guard robot, we show the effectiveness of the proposed reward.

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A high performance liquid chromatographic method for the simultaneous determination of the cyanogenic glycosides, i. ., amygdalin (AM) and prunasin (PR), and their degradation products, i. ., benzaldehyde (BAL) and benzoic acid (), in processed foods containing ume (Japanese apricot Prunus mume Sieb et Zucc.) was developed.
The sample was extracted with 0.05M citric acid solution and cleaned up by use of a Seppak C₁₈ cartridge. The extract was chromatographed on a Capcell Pak C₁₈ SG120 column with acetonitrile-water-0.2M phosphate buffer, pH 4.0 (16: 79: ). Detection was achieved with a UV monitor set at 210nm. The peaks corresponding to AM and PR were confirmed by examination of the effect of emulsin treatment.
The recoveries from ume extract, umeboshi (dried and salted ume), umeshu (Japanese apricot wine) and ume jam fortified with AM, PR, BAL and at levels of 40-100μg/g each were .-100.6% (C. V. 3.7-7.7%) for AM, 69.-105.3% (0.-4.2%) for PR, 71.-.0% (1.8-2.6%) for BAL and 82.7-99.1% (0.8-4.8%) for , except for AM in the ume extract and the umeboshi. AM in ume extract and umeboshi could not be determined owing to interference by contaminants.
The determination limits were 10μg/g for AM, 2μg/g for PR, and 1μg/g for BAL and , respectively.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 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-3β,,6β-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MC3T3-1 cells were increased 3.0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, 3, and 6 did not induce MC3T3-1 cell ALP activity at 0.1—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 MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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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 M1-2 mixing ratio δ, and the 0-2 mixing ratio μ_k are obtained for 818.7 keV +→2₁⁺ transition to be δ=1.52−

0.22

+0.26, and μ_k≤6.1×10⁻⁴ respectively. The

E

2 branching ratio B(

E

2;

2₂

+→0_g⁺): B(

E

2;

2₂

+→2₁⁺): B(

E

2;

2₂

+→0₁⁺) is determined to be 0.0158:1.0:

5

.

86

.

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Activity-directed isolation of the ethyl acetate, methylene chloride and n-hexane fractions of Gloiopeltis furcata resulted in the isolation of 18 compounds. Their structures were elucidated as 2-(3-hydroxy--oxotetrahydrofuran-3-yl)acetic acid (1), glutaric acid (2), succinic acid (3), nicotinic acid (4), ()-4-hydroxyhex-2-enoic acid (), cholesterol (6), 7-hydroxycholesterol (7), uridine (8), glycerol (), -(hydroxymethyl)-2-methoxybenzene-1,3-diol (10), (,)--oxodeca-,7-dienoic acid (11), (Z)-3-ethylidene-4-methylpyrrolidine-2,-dione (12), dehydrovomifoliol (13), loliolide (14), cholesteryl stearate (15), palmitic acid (16), cis-,8,11,14,17-eicosapentaenoic acid (17) and α-linolenic acid (18) on the basis of spectroscopic and chemical evidences. Their anticholinesterase and antioxidant activities were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as well as scavenging activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO⁻). All isolated compounds (1—18) exhibited moderate AChE inhibitory activities with IC₅₀ values ranging from 1.14—12.50 μg/ml, whereas 1, 7, , 17, and 18 showed mild BChE inhibitory activities with IC₅₀ values ranging from .57—15.89 μg/ml. Although most of the compounds isolated were lacking the scavenging activity on DPPH radical and ONOO⁻, and 10 showed good DPPH radical scavenging activity, and , 10, and 16 showed potent ONOO⁻ scavenging activity.

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The dual stage actuation (DSA) is one of the most attractive methods for increasing the track density of hard disk drives (HDDs). We have developed a φ-shaped actuated suspension as a fine actuator for a DSA system. The developed suspension's main resonance frequency was higher than kHz, its generated displacement was larger that 1-6 m at an applied voltage of 30 V and its shock resistance was greater than 3000 G. Flying-height variance caused by DSA driving (+/- V) was less than 1.3 % of nominal flying-height. The decrease of displacement was almost constant, less than % after 1 driving-cycles under heavy conditions (+/- 30V at 100℃, +/- 30V at ℃ and % humidity). Based on these data, we concluded that our actuated suspension can maintain a stable flying-height during its operation and its lifetime is as long as other actuators for HDDs.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about % of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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Eight new sterols, , 8α-epidioxy-(, 24R)-23-methylergosta-6, -dien-3β-ol (1), 3β, , -trihydroxy-(, 24R)-23-methylergosta-7, -dien-6-one (2), 3β, , -trihydroxy-(24S)-ergost-7-en-6-one (3), 3β, , , 14α-tetrahydroxy-(, 24R)-ergosta-7, -dien-6-one (4), (, 24R)-ergosta-7, -diene-3β, , 6α, -tetrol (), , -epidioxy-3β-hydroxy-(, 24R)-ergosta-7, -dien-6-one (6), , -epidioxy-3β-hydroxy-(24S)-ergost-7-en-6-one (7) and , 6α-epoxy-(, 24R)-ergosta-8, -diene-3β, 7β, 14α-triol (8), 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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Approximately 99% of the fat in huma milk is secreted into the alveoli by the mammary secretory epithelial cell (lactocyte) in membrane bound milk fat globules (MFG). The MFG, unlike small molecules such as lactose, have little effect on the osmotic balance between milk and blood and therefore they can be stored in large amounts in the alveolar lumen.Approximately 98% of the fat in the MFG are tri-acylglycerols (TAG). Importantly, different species, . g. women, rabbits, cows and elephants, have distinctive combinations of fatty acids esterified as TAG in their milk.We have measured 24-h milk production, fat content and fatty acid composition at 1, 2, 4, 6, , and 12 months of lactation in women.Mean (±SD) milk production (375.-1: 153.mL/24-h/breast) differed between breasts, between women and with stage of lactation (p<0.05). Whereas the fat content (35.±7.g/L) and the percentage composition of 18: 1n (32.24±3.3), 18: 2n6 (.18±2.66), 18: 3n3 (0.76±0.21), 20: 4n6 (0.37±0.07), : n3 (0.17±0.04), and : 6n3 (0.2±0.07) differed only between women and with stage of lactation (p<0.05).In contrast, the amount delivered to the infant differed (p<0.05) between women only for 18: 3n3, : n3 and : 6n3 and no differences in amounts delivered were observed for any of these fatty acids from 1 to 12 months of lactation.Each child received a mean (±SD) of 8.27-2. g 18: 1n; 2.38±0.98g 18: 2n6;194±73mg 18: 3n3;92±31mg 20: 4n6;43±14 mg : n3 and 49±21 mg : 6n3 every 24-h from breastmilk over the first year of life.These results indicate that variation in percentage composition of individual fatty acids (.g.18: 2n6) does not always translate to variation in the amount delivered to the infant.
Milk fat not only accounts for approximately 50% of the infant's energy intake, but also is responsible for the supply of the essential and long-chain polyunsaturated fatty acids that are required for the optimal development of the infant.For example, arachidonic acid (20: 4n6) and eicosapentaenoic acid (20: n3) are essential precursors for the synthesis of prostaglandins and immunomodulatory eicosanoids.On the other hand, docosahexaenoic acid (: 6n3, DHA) is a major polyunsaturated fatty acid in the membranes of the cerebral cortex and retina and higher intakes of DHA have been associated with higher ratings in intelligence tests particularly in children born prematurely. Fatty acids and mono-acylglycerols released by hydrolysis of TAG in the infant's digestive tract have a detergent like lytic action and inactivate enveloped viruses, gram positive and gram negative bacteria, fungi and protozoa.The membrane surrounding the human MFG contains mucin filaments that may act as a decoy to pathogenic micro-organisms ( coli).Micro-organisms recognise mucin filaments as membrane docking sites from which to launch an invasive infection and are thereby lured away from the membrane docking sites on the epithelial cells lining the infant's digestive tract.
Despite the importance of milk fat to the infant, it is the most variable component of human milk.It varies, over the course of a feed, over the course of the day, with stage of lactation, from one lactation to the next, between breasts, and between women. The major predictors of the fat content of milk over the course of a day have been shown to be the length of the interval between breastfeeds, the fat content at the end of the previous breastfeed, the amount of milk removed at the previous breastfeed and the amount of milk removed at the current feed.However, we have found that the fat content of milk is determined primarily by the amount of milk (degree of fullness) in the breast.For example, if the baby sleeps overnight, the mother's breasts will be full of milk in the morning and the fat content of fore-milk (milk obtained before a breastfeed) will be very low.

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The small strain stiffness and anisotropic nature of two sands with different geological origin have been determined via laboratory seismic tests performed in a triaxial cell. Dry triaxial reconstituted specimens of Ticino river silica sand (TS) and of Kenya carbonatic sand (KS) were subjected to isotropic and anisotropic states of effective stress ; then both shear and constrained compression waves were propagated in vertical, horizontal and oblique directions by means of five couples of piezoelectric transducers especially arranged in the specimens. The propagated compression and shear waves allow the assessment of the constrained M₀ and shear G₀ moduli respectively, at very small strains where, as a first approximation many soils can be assumed, from an engineering point of view, to behave as an elastic cross-anisotropic medium with a vertical axis of symmetry. This paper, after a brief description of the novel measuring technique adopted and of the tested materials, summarises the test results and their interpretation in order to separate the effects of the fabric anisotropy from those produced by the state of effective stresses on soil stiffness. The stiffness and anisotropic response of the two tested sands are compared. Finally the results enable us to establish five independent constants of the cross-anisotropic elasticity model, which appears to be appropriate to reproduce the behaviour at small strain of the two sands.

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