A series of magnon crystals appearing under ultrahigh magnetic fields in a kagomé antiferromagnet.

Geometrical frustration and a high magnetic field are two key factors for realizing unconventional quantum states in magnetic materials. Specifically, conventional magnetic order can potentially be destroyed by competing interactions and may be replaced by an exotic state that is characterized in terms of quasiparticles called magnons, the density and chemical potential of which are controlled by the magnetic field. Here we show that a synthetic copper mineral, Cd-kapellasite, which comprises a kagomé lattice consisting of corner-sharing triangles of spin-1/2 Cu2+ ions, exhibits an unprecedented series of fractional magnetization plateaus in ultrahigh magnetic fields of up to 160 T. We propose that these quantum states can be interpreted as crystallizations of emergent magnons localized on the hexagon of the kagomé lattice.

Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats.

Theanine (gamma-glutamylethylamide) is one of the major amino acid components in green tea and can pass through the blood-brain barrier. Recent studies suggest that theanine affects the mammalian central nervous system; however, the detailed mechanism remains unclear. In this study, we demonstrated the effect of theanine on neurotransmission in the brain striatum by in vivo brain microdialysis. Theanine injection into the rat brain striatum did not increase the concentration of excitatory neurotransmitters in the perfusate. On the other hand, theanine injection increased the concentration of glycine in the perfusate. Because it has been reported that theanine promotes dopamine release in the rat striatum, we investigated the glycine and dopamine concentrations in the perfusate. Co-injection of glycine receptor antagonist, strychnine, reduced theanine-induced changes in dopamine. Moreover, AMPA receptor antagonist, which regulates glycine and GABA release from glia cells, inhibited these effects of theanine and this result was in agreement with the known inhibitory effect of theanine at AMPA receptors.

Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities.

OBJECTIVE: We examined whether green tea-extract powder supplementation improves glucose abnormality. METHODS: The study was conducted for volunteers who resided in eastern communities of Shizuoka Prefecture and who had fasting blood glucose levels of >or=6.1 mmol/l or nonfasting blood glucose levels of >or=7.8 mmol/l in a recent health check-up. Sixty subjects aged 32-73 years (49 males and 11 females) participated in the trial. The Early intervention group consumed a packet of green tea-extract powder containing 544 mg polyphenols (456 mg catechins) daily for the first 2 months and then entered the 2-month nonintervention period. The Later intervention group was observed for the first 2 months and then consumed green tea-extract powder as described above for the subsequent 2 months. Using the two-period crossover design, we analyzed the changes in fasting hemoglobin A1c level and other biomarkers in blood samples collected at baseline, 2 months and 4 months. RESULTS: A significant reduction in hemoglobin A1c level and a borderline significant reduction in diastolic blood pressure were associated with the intervention. The intervention caused no significant changes in weight, body mass index, body fat, systolic blood pressure, fasting serum glucose level, homeostasis model assessment index, serum lipid level or hypersensitive C-reactive protein. CONCLUSION: Daily supplementary intake of green tea-extract powder lowered the hemoglobin A1c level in individuals with borderline diabetes.

Cardioprotective effect of edaravone against ischaemia-reperfusion injury in the rabbit heart before, during and after reperfusion treatment.

The free radical scavenger edaravone is able to stimulate prostacyclin release and inhibit the lipoxygenase pathway in the arachidonic acid cascade. The effect of edaravone administration on myocardial damage in rabbit hearts subjected to ischaemia-reperfusion was examined at different times relative to reperfusion. All rabbits underwent sustained coronary artery occlusion for 30 min followed by 3 h of reperfusion. Rabbits were divided into the following groups: control; early (3 mg/kg edaravone IV 10 min before reperfusion); immediate (3 mg/kg edaravone IV immediately after the start of reperfusion); and late (3, 6 or 10 mg/kg edaravone IV 5 min after the start of reperfusion). Single bolus administration of edaravone 10 min before reperfusion or immediately upon initiation of reperfusion appears to be associated with reductions in infarction size and the percentage of apoptotic cells, but treatment with edaravone 5 min after initiation of reperfusion does not appear to have this protective effect.

A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with weakness N of one and responder restricted design.

OBJECTIVE: To evaluate the effects of Hochuekkito, a traditional Japanese and Chinese medicine, in the treatment of elderly patients with general weakness. To devise a suitable study design for assessing the clinical effectiveness of traditional herbal medicines. METHODS: Fifteen elderly patients (mean +/- SD: age 78.4 +/- 7.8; m/f 3/12) participated in this study. A multicenter, prospective, randomized, double-blind, placebo-controlled study with N of one and responder restricted design was performed. After the run-in period, the patients were divided into responders and non-responders. Only responders were entered in the study, and were randomized into three groups: an active-placebo group, a placebo-active group and an active-active group. The study consisted of two 6-week terms with a 2-week washout period in between. We assessed the Short Form 36 Health Survey (SF-36) and Profile of Mood States (POMS) as an endpoint of quality of life (QOL). In addition, we assessed the biodefense status by measuring the natural killer cytolytic activity (NK activity), IL-2 producing activity of peripheral lymphocytes, lymphocyte proliferating activity and lymphocyte cell-surface antigens. RESULTS: The physical component summary of the SF-36 analysis significantly improved in the Hochuekkito-treated group. Four components (A-H: anger-hostility, F: fatigue, T-A: tension-anxiety, C: confusion) out of six improved in the Hochuekkito-treated group in the POMS analysis. Lymphocyte proliferating activity improved in the Hochuekkito-treated group but not significantly. Concerning the surface antigens of peripheral lymphocytes, the population of CD3 positive cells and CD3CD4 double positive cells increased in the Hochuekkito-treated group. CONCLUSION: We revealed that Hochuekkito improved the QOL and immunological status of elderly patients with weakness by randomized controlled trial. Our study design might be useful for assessing the efficacy of traditional herbal medicine in the future.

Modulation of aromatase expression in human breast tissue.

Aromatase plays an important role in breast cancer development through its role in the synthesis of estrogen. Aromatase expression in breast tissue can be regulated by several mechanisms. The major promoter usage for aromatase expression in breast tumors (i.e. cAMP-stimulated promoters I.3 and II) is different from that in normal breast tissue (i.e. glucocorticoid-stimulated promoter I.4). Recent characterization of transcription factors that interact with the two important regulatory elements near promoters I.3 and II, i.e. S1 and CREaro, helps us better understand the mechanism of the switch of promoter usage between normal breast tissue and cancer tissue. It is thought that in normal breast tissue, the function of promoters I.3 and II is suppressed through the binding of EAR-2, COUP-TFI, and EARgamma to S1, and through the binding of Snail/Slug proteins to their binding site that quenchs the CREaro activity. In cancer tissue, the expression levels of EAR-2, COUP-TFI, EARgamma, Snail, and Slug decrease, and aromatase expression is then up regulated through the binding of ERRalpha-1 to S1 and the binding of CREB or related factors to CREaro. Results from this and other laboratories reveal that aromatase activity in aromatase expressing cells can also be modified by treatment with aromatase inhibitors and the antiestrogen ICI 182, 780. While aromatase inhibitors are used to treat breast cancer, the treatment has been found to increase the level of aromatase in the breast tissue of some patients. The enhancement of aromatase activity by aromatase inhibitors is thought to be due to a decrease of aromatase protein degradation by enzyme-inhibitor complex formation, up-regulation of the aromatase gene transcription through a cAMP-mediated mechanism, and an induction of aromatase expression by gonadtropins that are released from the pituitary in response to a reduction of estrogen levels in circulation in premenopausal women. Antiestrogen ICI 182, 780 has been found to suppress aromatase expression, but the mechanism has not yet been determined. In addition, aromatase activity and expression can be affected by environmental chemicals. A detailed structure-function study has revealed that flavones, but not isoflavones, are inhibitors of aromatase. It was found that flavones bind to the active site of aromatase in an orientation in which their rings-A and -C mimic rings-D and -C of the androgen substrate. The modulation of aromatase expression by endocrine disrupting chemicals is exemplified by two organochlorine pesticides (i.e. toxaphene and chlordane) that have been found to be antagonists of ERRalpha-1 orphan receptor. These compounds reduce ERRalpha-1 activity, resulting in a suppression of aromatase expression.

The inhibition of phenylhydroquinone-induced oxidative DNA cleavage by constituents of Moutan Cortex and Paeoniae Radix.

Moutan Cortex (root cortex of Paeonia suffruticosa ANDREWS) and Paeoniae Radix (root of Paeonia lactiflora PALLAS) are crude drugs used in many traditional prescriptions and have constituents in common. We studied the effects of extracts of these crude drugs and their constituents on oxidative DNA damage caused by phenylhydroquinone (PHQ), a major metabolite of o-phenylphenol. Both drugs suppressed the cleavage of pUC18 DNA induced by PHQ, and scavenged the superoxide and hydroxy radical generated by the chemical. They also inhibited the oxidative DNA cleavage by tert-butylhydroquinone (TBHQ), one of the major metabolites of butylated hydroxyanisole. When constituents were examined with the same system, galloylpaeoniflorin and 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) were found to be the most potent inhibitors of the DNA cleavage. These constituents had oxygen radical scavenging activity. Paeonol also attenuated the DNA cleavage. Paeoniflorin and albiflorin had relatively small inhibitory effects on DNA cleavage. However, catechin enhanced the PHQ-induced DNA cleavage. The suppression of oxidative DNA damage by Moutan Cortex and Paeoniae Radix might be attributable to the additive effects of galloylpaeoniflorin, PGG and other constituents.

Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.

The effect of green tea catechin supplementation on antioxidant capacity of human plasma was investigated. Eighteen healthy male volunteers who orally ingested green tea extract (254 mg of total catechins/subject) showed 267 pmol of epigallocatechin-3-gallate (EGCg) per milliliter of plasma at 60 min after administration. The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans.

Suppressive effects of Hochu-ekki-to, a traditional Chinese medicine, on IgE production and histamine release in mice immunized with ovalbumin.

We examined the effects of Bu-Zhong-Yi-Qi-Tang (Japanese name: Hochu-ekki-to, HET), a traditional Chinese medicine, on IgE production and histamine release in mice immunized intraperitoneally with a mixture of ovalbumin (OA) and aluminum hydroxide (alum adjuvant). Three groups of mice were orally administered 0, 1.7 or 17 mg of HET on day 13 after the first immunization with a mixture of 1 microg OA and 1 mg alum adjuvant. They were again immunized with the same dose of OA plus alum adjuvant on day 14. The immunological changes in mice treated with OA alone or OA plus HET were examined, and the following findings were obtained. In the HET-treated mice, the elevation of anti-OA IgE in serum, and histamine release from basophils in blood, were significantly suppressed. A significant suppression of interleukin-4 (IL-4) secretion and proliferation of splenic lymphocytes in primary culture was also observed. A tendency to suppress the elevation of anti-OA IgG1 in serum and interleukin-2 (IL-2) secretion from splenic lymphocytes was observed in the HET-treated mice. These findings suggest that oral administration of HET suppresses IgE antibody production and histamine release in type I allergic reaction in mice immunized with OA plus alum adjuvant; this shows the efficacy of HET in treating type I allergic diseases, such as asthma.

Epigallocatechin gallate and gallocatechin gallate in green tea catechins inhibit extracellular release of Vero toxin from enterohemorrhagic Escherichia coli O157:H7.

We studied the effects of six catechin derivatives (catechin, epigallocatechin, epicatechin, epicatechin gallate, epigallocatechin gallate (EGCg) and gallocatechin gallate (GCg)) in green tea on the production and extracellular release of Vero toxins (VTs) from enterohemorrhagic Escherichia coli (EHEC) cultured at 37 degrees C for 24 h. EGCg and GCg in the culture medium markedly inhibited extracellular VTs release from EHEC cells into the culture supernatant fluid at concentrations of 0.05 mg/ml or higher, as estimated by both the reversed passive latex agglutination assay and cytotoxic assay using Vero cells. Production and extracellular release of maltose binding protein, a periplasmic protein, into the culture supernatant were also inhibited by EGCg and GCg, indicating that their inhibitory effect on release from periplasm into the outer milieu is not specific to VTs, but general to the proteins accumulated in EHEC periplasm.

In vitro pharmacological profile of nonpeptide CRF1 receptor antagonists, CRA1000 and CRA1001.

We investigated pharmacological properties of CRA1000 (2-(N-(2-methylthio-4-isopropylphenyl)-N-ethylamino-4-(4-(3-fluoro phenyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine) and CRA1001 (2-( N-(2-bromo-4-isopropylphenyl)-N-ethylamino-4-(4-(3-fluorophenyl)-1 ,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine), novel and selective antagonists for the corticotropin-releasing factor1 (CRF1) receptor. Both CRA1000 and CRA1001 inhibited [125I]ovine CRF binding to membranes of COS-7 cells expressing the rat CRF1 receptor with IC50 values of 30 and 38 nM, respectively, without affecting [125I]sauvagine binding to membranes of COS-7 cells expressing the rat CRF2alpha receptor. CRF elicited intracellular cyclic AMP (cAMP) accumulation in AtT-20 cells which express the CRF1 receptor but not the CRF2 receptor, and COS-7 cells expressing CRF1 or CRF2alpha receptors. The CRF-induced cAMP accumulation was inhibited by both CRA1000 and CRA1001, concentration-dependently, in AtT-20 cells and COS-7 cells expressing the CRF1 receptor, while these compounds did not attenuate the CRF response in COS-7 cells expressing the CRF2alpha receptor. CRF increased adrenocorticotropin (ACTH) secretion from AtT-20 cells, and CRA1000 and CRA1001 inhibited CRF-induced ACTH secretion, concentration-dependently, as did other CRF1 receptor antagonists. These results show that both CRA1000 and CRA1001 are potent and selective CRF1 receptor antagonists.

Simultaneous determination of catechins in human saliva by high-performance liquid chromatography.

Green tea extracts have been suggested to possess a preventive effect against dental caries. A quantitative method for their anticariogenic substances, catechins, was developed to evaluate their concentrations in human saliva after mouthrinsing with green tea extract. Salivary catechins were extracted to the organic phase after forming a complex with diphenylborate and an ion-pair with tetra-n-butylammonium, and then back-extracted to the acidic aqueous phase. The extract was analyzed by high-performance liquid chromatography using diode array detection at absorption wavelengths ranging from 269 to 278 nm. In reversed-phase chromatography by a gradient elution, eight catechins originating from green tea and an internal standard were separated in 15 min without interfering peaks. All the catechins were simultaneously and selectively determined in the concentration range 0.05-25.0 microg/ml. In replicate spiking experiments with standards, the mean recovery ranged between 86 and 99%, and both intra- and inter-assay C.V.s were within 2.3%. When mouthrinsing with an aqueous solution of green tea extract (5.0 mg/ml) containing eight catechins, the quantitative results revealed that each catechin was retained at microg/ml levels in saliva for up to 60 min.

[A case of advanced gastric remnant carcinoma with Virchow's metastasis treated with neoadjuvant chemotherapy (low dose CDDP + 5-FU) followed by surgical resection].

The patient was a 64-year-old woman. At hospitalization she had gastric remnant carcinoma with Virchow's and paraaortic lymph node metastases, extensive local infiltration and obstructive jaundice. The lesions were considered nonresectable, and the patient was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU, which resulted in the disappearance of Virchow's and paraaortic lymph node metastases. She was considered to have a partial response (PR) and underwent lower esophageal resection, total remnant gastrectomy and splenectomy. Eight months after surgery, however, she died of disseminated carcinomatosis of bone marrow. Since this therapy was associated with only slightly adverse events (< or = Grade 1), this treatment modality appears to be safe. However, further studies will be necessary to identify what type of recurrence is responsive to this therapy and to evaluate its effect on patient survival.

Radiographic and endoscopic features of colonic ulcers in systemic lupus erythematosus.

The radiographic and endoscopic features of the colonic ulcers during the course of a case of systemic lupus erythematosus are illustrated. Barium enema revealed the "collar button" type of penetrating ulcers in the left half of the colon and endoscopy demonstrated multiple round- or oval-shaped discrete ulcers, so-called "punched-out" ulcers with pale mucosa. These findings are compared with those of the reported cases of systemic lupus erythematosus and ulcerative colitis. Steroid and 6-mercaptopurine therapy was effective in this case.