New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline.

BACKGROUND: In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported. AIM: In this study, we evaluated the efficacy of H2-receptor antagonist (famotidine) and 5-HT4 receptor agonist (mosapride citrate). In addition, the effect of antidepressants was assessed as the second-step therapy. METHODS: Patients complaining upper GI symptoms were diagnosed as FD excluding organic diseases. Randomized patients received 20 mg/day of famotidine or 15 mg/day of mosapride citrate for 4 weeks and the efficacy was compared between the two groups based on a 10-point visual analogue scale. When symptoms were not relieved (score improvement 0-2 points), patients received amitriptyline (30 mg/day) or no medication for 4 weeks randomly. Patients who had depression in psychological test (SDS) were omitted. RESULTS: As the first-step therapy, both famotidine and mosapride showed beneficial effects regardless of FD subtypes, age and gender. The efficacy of these two drugs in relieving FD symptoms was not significantly different. In patients who failed in the first-step therapy, amitriptyline showed beneficial effects. CONCLUSIONS: These findings might be clinically important in view of the efficient relief of symptoms in FD patients.

Acylated anthocyanidin 3-sophoroside-5-glucosides from Ajuga reptans flowers and the corresponding cell cultures.

Four anthocyanins from Ajuga reptans flowers and its cell cultures were isolated, and a fifth was also characterized by HPLC-mass spectrometry. By means of chemical and spectroscopic analyses, their structures were identified as delphinidin 3-(p-coumaroyl-feruloyl)sophoroside-5-malonylglucoside, delphinidin 3-(diferuloyl)sophoroside-5-malonylglucoside, and cyanidin 3-(di-p-coumaroyl)sophoroside-5-glucoside, respectively. The other two were tentatively identified as delphinidin 3-(diferuloyl)sophoroside-5-glucoside and cyanidin 3-(feruloyl-p-coumaroyl)sophoroside-5-malonylglucoside. In neutral aqueous solution, the crude extract from A. reptans flower cell cultures and the major anthocyanin cyanidin 3-(di-p-coumaroyl)sophoroside-5-malonylglucoside were more stable than cyanidin 3-glucoside, and also prevented more efficiently peroxidation than did the latter. A. reptans flower cell culture anthocyanins may have a potential as natural colorants for food utilities or other purposes.

Antihypertensive effect of ACE inhibitory oligopeptides from chicken egg yolks.

Oligopeptides of 1 KDa or less were obtained by hydrolysis of chicken egg yolks with a crude enzyme, and by dialysis with a semipermeable membrane filter. Since the extracted peptides had an inhibitory action on the activity of angiotensin I-converting enzyme (ACE) in vitro, they were orally administered at 20, 100 and 500 mg/kg body weight to spontaneously hypertensive rats (SHR) for 12 weeks to analyze the physiological role on cardiovascular functions. The administered oligopeptides suppressed the development of hypertension at all dosages. After 12 weeks at 500 mg/kg body weight, the values for systolic, mean, and diastolic blood pressure were approximately 10% less in SHRs administered than controls. Furthermore, serum ACE activity of the peptide-administered groups was significantly lower than that of the control group in a dose-related manner. Our results imply that oligopeptides extracted from hen's egg yolks could potentially suppress the development of hypertension in SHR, and this effect might be induced by the inhibition of ACE activity.

Effects of a Small Inclination Misalignment in Talbot Interferometry by use of Gratings with Arbitrary Line Orientation. I. Theoretical Analysis.

We discuss the effects of a general small inclination misalignment, which is formed by rotation of the beam-splitter grating around an axis that is laid on the grating plane and that has an arbitrary angle with respect to the line direction of the grating, between the two grating planes on the moiré fringes in Talbot interferometry. It is shown that the small inclination angle has a significant influence on measurement results based on Talbot interferometry because both the period and the slope of the moiré fringes are sensitive to the angle, especially when the rotation axis is nearly parallel to the lines of the grating. Simple and practical detection methods for the small inclination angle are proposed, and the effects of the inclination angle on the contrast in the moiré fringes are also briefly discussed.

Effects of a Small Inclination Misalignment in Talbot Interferometry by Use of Gratings with Arbitrary Line Orientation. II. Experimental Verification.

The theoretical results of the effects of a small inclination misalignment, which is formed by rotation of the beam-splitter grating around the axis on the grating plane when the axis has an arbitrary angle with respect to the line direction of the grating, between the two grating planes on the moiré fringes in the Talbot interferometry are verified by experiment. The experimental results coincide well with theoretical ones. Consequently, the effect of the small arbitrary inclination on practical measurements based on the Talbot interferometry is further explained by an example that examines the beam collimation of a lens, and the advantages and limitations of the effect are also discussed.

General inclination effects produced by a beam-splitter grating in talbot interferometry with crossed gratings.

The effects of an arbitrary small inclination between the two crossed gratings on moiré fringes in Talbot interferometry are discussed. The small inclination is formed by the rotation by a small angle gamma of the beam splitter's grating about the axis that is on the plane of the grating and has an arbitrary angle delta with respect to the lines of the grating. The results indicate that the small inclination has a great influence on measurements for which Talbot interferometry is applied, such as beam collimation and measurement of the focal length of a lens. The theoretical analyses are proved by experimental results. Some methods for judging the size of a small inclination are also proposed.

Effects of pH and light on the storage stability of the purple pigment, hordeumin, from uncooked barley bran fermented broth.

The pigment retention rate of hordeumin was higher than that of two standard anthocyanidins, cyanidin and delphinidin, when hordeumin and anthocyanidins were dissolved in Walpole buffer (pH 1.0) and stored. Moreover, when pigment solutions were stored at 15 degrees C under light irradiation, the pigment retention rate of the hordeumin solution became higher than those of standard anthocyanidins (2 to 10 times) as the storage period increased. Comparing various pH buffers (MacIlvaine buffer, pH 2.2 to 7.0), the pigment retention rate of hordeumin at pH 5.0 was highest. Furthermore, the half-life of hordeumin at pH 5.0 was increased from 9 days to 17.5 days when nitrogen gas was bubbled into the hordeumin solution. We considered that the storage stability of hordeumin is higher than standard anthocyanidins because hordeumin is a complex with anthocyanin, tannin, and protein.

Developmentally regulated rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila.

A clear relationship exists between histone acetylation and transcriptional output, the balance of which is conferred by opposing histone acetyltransferases (HATs) and histone deacetylases (HDACs). To explore the role of HDAC activity in determining the transcriptional competency of chromatin, we have exploited the biological features of Tetrahymena as a model. Each vegetative cell contains two nuclei: a somatic, transcriptionally active macronucleus containing hyperacetylated chromatin and a transcriptionally silent, germ line micronucleus containing hypoacetylated histones. Using a PCR-based strategy, a deacetylase gene (named THD1) encoding a homolog of the yeast HDAC Rpd3p was cloned. Thd1p deacetylates all four core histones in vitro. It resides exclusively in the macronucleus during vegetative growth and is asymmetrically distributed to developing new macronuclei early in their differentiation during the sexual pathway. Together, these data are most consistent with a potential role for Thd1p in transcriptional regulation and suggest that histone deacetylation may be important for the differentiation of micronuclei into macronuclei during development.

Radical scavenging activity of a purple pigment, hordeumin, from uncooked barley bran-fermented broth.

A novel purple pigment called hordeumin, a type of anthocyanin-tannin pigment, was produced from barley bran-fermented broth. The radical scavenging activity of hordeumin was analyzed by using an electron-spin resonance (ESR) spectrometer. The hordeumin scavenged superoxide radical in a concentration-dependent manner. Superoxide dismutase-like activity values were 118 and 195 units/mg for crude and partially purified hordeumin, respectively. The two types of hordeumins also scavenged the DPPH radical. Furthermore, barley bran-fermented filtrate before pigment formation and extract of barley bran also scavenged the DPPH radical. However, the DPPH radical scavenging activity of a filtrate, fermented over a long period, was stronger than that fermented over a short period. Thus, it was considered that radical scavenging activity of hordeumin resulted from barley bran polyphenol such as proanthocyanidins.

High-performance affinity beads for identifying drug receptors.

We have developed a method using novel latex beads for rapid identification of drug receptors using affinity purification. Composed of a glycidylmethacrylate (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize nonspecific protein binding and maximize purification efficiency. We demonstrated their performance by efficiently purifying FK506-binding protein using FK506-conjugated beads, and found that the amount of material needed was significantly reduced compared with previous methods. Using the latex beads, we identified a redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug, E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB drugs. Our results suggest that the latex beads could provide a tool for the identification and analysis of drug receptors and should therefore be useful in drug development.

Antimutagenicity of the purple pigment, hordeumin, from uncooked barley bran-fermented broth.

The novel purple pigment hordeumin, an anthocyanin-tannin pigment, was produced from barley bran-fermented broth. The mutagenicity or antimutagenicity of hordeumin was investigated according to the Ames method, an indication of the safety of food, using Salmonella typhimurium TA98. Despite the presence of S-9 mix, hordeumin was not mutagenic. On the other hand, hordeumin effectively decreased a reverse mutation from Trp-P-1, Trp-P-2, IQ, and B[a]P. Furthermore, hordeumin also decreased the reverse mutation from dimethyl sulfoxide extracts of grilled beef.

Effects of Unparallel Grating Planes in Talbot Interferometry. II.

The properties of the moiré fringes in Talbot interferometry are analyzed for a small inclined angle beta between the two grating planes, which is produced by rotation of the beam splitter grating about the axis perpendicular to the lines of the grating. Theoretical analyses indicate that the tilt angle of the resultant moiré fringes is less sensitive to beta than when the small inclined angle is formed by rotation of the beam splitter grating about the axis parallel to the lines direction of the grating as described earlier [Appl. Opt. 38, 4111 (1999)] and that contrast of the moiré fringes decreases with an increase in beta or in the spatial frequency of the grating and may result in impaired measurement accuracy. The validity of the theoretical analyses is illustrated by experiments.

Influence of unparallel grating planes in talbot interferometry with cross gratings of different spatial frequencies in two directions.

The effects of an arbitrary small inclination between two cross gratings on the moiré fringes in Talbot interferometry are discussed when the frequencies of the grating differ in two perpendicular directions. We show that the small angles, alpha and beta, by which the beam-splitter cross grating is rotated around the two axes parallel to the two perpendicular line directions of the cross grating, have a greater influence on the moiré fringes with cross gratings than that with one-dimensional gratings. A simple and practical detection method for the angles between the two unparallel grating planes in Talbot interferometry is also proposed. The theoretical analyses are proved by experimental results.

Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena.

Studies into posttranslational modifications of histones, notably acetylation, have yielded important insights into the dynamic nature of chromatin structure and its fundamental role in gene expression. The roles of other covalent histone modifications remain poorly understood. To gain further insight into histone methylation, we investigated its occurrence and pattern of site utilization in Tetrahymena, yeast, and human HeLa cells. In Tetrahymena, transcriptionally active macronuclei, but not transcriptionally inert micronuclei, contain a robust histone methyltransferase activity that is highly selective for H3. Microsequence analyses of H3 from Tetrahymena, yeast, and HeLa cells indicate that lysine 4 is a highly conserved site of methylation, which to date, is the major site detected in Tetrahymena and yeast. These data document a nonrandom pattern of H3 methylation that does not overlap with known acetylation sites in this histone. In as much as H3 methylation at lysine 4 appears to be specific to macronuclei in Tetrahymena, we suggest that this modification pattern plays a facilitatory role in the transcription process in a manner that remains to be determined. Consistent with this possibility, H3 methylation in yeast occurs preferentially in a subpopulation of H3 that is preferentially acetylated.

A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme.

The elongator complex is a major component of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation in yeast. Here we identify Elp3, the 60-kilodalton subunit of elongator/RNAPII holoenzyme, as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro. In vivo, ELP3 gene deletion confers typical elp phenotypes such as slow growth adaptation, slow gene activation, and temperature sensitivity. These results suggest a role for a novel, tightly RNAPII-associated HAT in transcription of DNA packaged in chromatin.

A novel H2A/H4 nucleosomal histone acetyltransferase in Tetrahymena thermophila.

Recently, we reported the identification of a 55-kDa polypeptide (p55) from Tetrahymena macronuclei as a catalytic subunit of a transcription-associated histone acetyltransferase (HAT A). Extensive homology between p55 and Gcn5p, a component of the SAGA and ADA transcriptional coactivator complexes in budding yeast, suggests an immediate link between the regulation of chromatin structure and transcriptional output. Here we report the characterization of a second transcription-associated HAT activity from Tetrahymena macronuclei. This novel activity is distinct from complexes containing p55 and putative ciliate SAGA and ADA components and shares several characteristics with NuA4 (for nucleosomal H2A/H4), a 1.8-MDa, Gcn5p-independent HAT complex recently described in yeast. A key feature of both the NuA4 and Tetrahymena activities is their acetylation site specificity for lysines 5, 8, 12, and 16 of H4 and lysines 5 and 9 of H2A in nucleosomal substrates, patterns that are distinct from those of known Gcn5p family members. Moreover, like NuA4, the Tetrahymena activity is capable of activating transcription from nucleosomal templates in vitro in an acetyl coenzyme A-dependent fashion. Unlike NuA4, however, sucrose gradient analyses of the ciliate enzyme, following sequential denaturation and renaturation, estimate the molecular size of the catalytically active subunit to be approximately 80 kDa, consistent with the notion that a single polypeptide or a stable subcomplex is sufficient for this H2A/H4 nucleosomal HAT activity. Together, these data document the importance of this novel HAT activity for transcriptional activation from chromatin templates and suggest that a second catalytic HAT subunit, in addition to p55/Gcn5p, is conserved between yeast and Tetrahymena.

Effects of unparallel grating planes in Talbot interferometry.

The properties of moiré fringes in Talbot interferometry are analyzed when the angle between the two grating planes is small. The results indicate that the tilt angle of the moiré fringes, observed just behind the test grating, is sensitive to the small angle. Based on this sensitivity, several features of parallelism of the two grating planes are presented, and the influence of the small angle when checking the beam collimation of a lens is also discussed. The validity of the theoretical analysis is illustrated by experiment.

Effects of Reactive Oxygen and Temperature on the Formation of a Purple Pigment, Hordeumin, from Barley Bran-Fermented Broth.

A purple pigment called hordeumin, a type of anthocyanin-tannin pigment, is produced from barley barn-fermented broth. Hordeumin is a precipitate formed by storing fermented filtrate containing hordeumin precursors in an oxidative environment. Hordeumin formation was inhibited by addition of radical scavengers or antioxidants to the barley bran-fermented filtrate. The addition of iron ion accelerated hordeumin formation, and the addition of DETAPAC, an iron ion chelating reagent, influenced the color tone of hordeumin. These findings suggest that hordeumin formation may be an oxygen-mediated reaction, involving reactive oxygen species. Furthermore, hordeumin formation was accelerated by increasing the hordeumin formation temperature (from 5 to 60°C). The color quality of the hordeumin that was produced at high temperature was almost the same as that hordeumin produced at 5°C.