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The discovery of new catalytic applications for metals remains an important goal in organic synthesis. If a catalyst has multiple functions, such as inducing bond cleavage and formation, it can streamline multi-step transformations. Herein, the Cu-catalyzed synthesis of imidazolidine through heterocyclic recombination between aziridine and diazetidine is reported. Mechanistically, Cu catalyzes the conversion of diazetidine into the corresponding imine, which then reacts with aziridine to form imidazolidine. The scope is sufficiently wide to form various imidazolidines, as many functional groups are compatible with the reaction conditions.
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When liquid alkane droplets are placed on a surfactant solution surface having a proper surface density, alkane molecules penetrated into the surfactant-adsorbed film to form a mixed monolayer. Such a mixed monolayer undergoes a thermal phase transition from two-dimensional liquid to solid monolayers upon cooling when surfactant tail and alkane have similar chain lengths. We applied the total-reflection XAFS spectroscopy and surface quasi-elastic light scattering to the mixed adsorbed film of cetyltrimethylammonium bromide and hexadecane to elucidate the impact on the surface phase transition on the counterion distribution of the mixed monolayer. The EXAFS analysis verified that a higher percentage of counter Br- ions were localized in the Stern layer than in the diffuse double layer in the surface solid film compared to the surface liquid film, which resulted in a reduction in the surface elasticity measured by the SQELS. The finding that the surface phase transition accompanies the change in the counterion distribution will be important to consider the future applications of the colloidal systems, in which the coexistence of a surfactant and alkane molecules is essential, such as foams and emulsions.
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Herein we report a copper-catalyzed synthesis of imidazolidine by employing the reaction of aziridine with imine. The reaction smoothly provided a diverse range of 2-substituted imidazolidines with high compatibility with various functional groups. Moreover, during our investigation, we discovered that isocyanate also reacted with aziridine to yield substituted imidazolidinones efficiently. The versatility of these reactions was further demonstrated by their application in the synthesis of hybrid molecules derived from two pharmaceutical compounds. This approach opens new possibilities for the discovery of novel classes of bioactive molecules.
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In nature, minerals record various origins and information for geology and geobiochemistry. Here, we investigated the origin of organic matter and growth mechanism of quartz with oil inclusion revealing fluorescence under short ultraviolet (UV) light, obtained from the clay vein at Shimanto-cho, Kochi, Shikoku Island, Japan. Geological investigation indicated that the oil-quartz was formed in hydrothermal metamorphic veins found in the late Cretaceous interbedded sandstone and mudstone. The obtained oil-quartz crystals are mostly double-terminated. Micro-X-ray computed tomography (microCT) indicated that oil-quartz crystals have various veins originating as skeleton structures along the quartz crystal {111} and {1-11} faces. Spectroscopic and chromatographic studies indicated that aromatic ester and tetraterpene (lycopene) molecules, which revealed fluorescence, were detected. Large molecular weight sterol molecules, such as C40, were also detected in the vein of oil-quartz. This investigation indicated that organic inclusions in mineral crystals would form with ancient microorganism culture environments.
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Helicobacter pylori (H. pylori) infection and high intake of various traditional salt-preserved foods are regarded as risk factors for human gastric cancer. We previously reported that Chinese cabbage contains indole compounds, such as indole-3-acetonitrile, a mutagen precursor. 1-Nitrosoindole-3-acetonitrile (NIAN), formed by the treatment of indole-3-acetonitrile with nitrite under acidic conditions, shows direct-acting mutagenicity. In the present study, NIAN administration by gavage to Mongolian gerbils (MGs) at the dose of 100 mg/kg two times a week resulted in three adduct spots (1.6 adducts/10(8) nucleotides in total), detected in DNA samples from the glandular stomach by (32) P-postlabeling methods. Treatment with six consecutive doses of 100 mg/kg of NIAN, two times a week for 3 weeks, induced well-and moderately-differentiated glandular stomach adenocarcinomas in the MGs at the incidence of 31% under H. pylori infection at 54-104 weeks. Such lesions were not induced in MGs given broth alone, broth + NIAN or infection with H. pylori alone. Thus, endogenous carcinogens formed from nitrosation of indole compounds could be critical risk factors for human gastric cancer development under the influence of H. pylori infection.
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Acetonitrilas/administração & dosagem , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/virologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/virologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Cocarcinogênese , Adutos de DNA/metabolismo , Esquema de Medicação , Gastrite/microbiologia , Gastrite/patologia , Gerbillinae , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Masculino , Organismos Livres de Patógenos Específicos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Nanocarbons, such as fullerenes, carbon nanotubes, and graphenes, have long inspired the scientific community. In order to synthesize nanocarbon molecules in an atomically precise fashion, many synthetic reactions have been developed. The ultimate challenge for synthetic chemists in nanocarbon science is the creation of periodic three-dimensional (3D) carbon crystals. In 1991, Mackay and Terrones proposed periodic 3D carbon crystals with negative Gaussian curvatures that consist of six- and eight-membered rings (the so-called Mackay-Terrones crystals). The existence of the eight-membered rings causes a warped nanocarbon structure. The Mackay-Terrones crystals are considered a "dream material", and have been predicted to exhibit extraordinary mechanical, magnetic, and optoelectronic properties (harder than diamond, for example). To turn the dream of having this wonder material into reality, the development of methods enabling the creation of octagon-embedding polycyclic structures (or nanographenes) is of fundamental and practical importance. This review describes the most vibrant synthetic achievements that the scientific community has performed to obtain curved polycyclic nanocarbons with eight-membered rings, building blocks that could potentially give access as templates to larger nanographenes, and eventually to Mackay-Terrones crystals, by structural expansion strategies.
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OBJECTIVE: A formula is needed that is practical for current livestock breeding methods and that predicts the approximate rate of inbreeding (∆F) in populations where selection is performed according to four-path programs (sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters). The formula widely used to predict inbreeding neglects selection, we need to develop a new formula that can be applied with or without selection. METHODS: The core of the prediction is to incorporate the long-tern genetic influence of the selected parents in four-selection paths executed as sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters. The rate of inbreeding was computed as the magnitude that is proportional to the sum of squared long-term genetic contributions of the parents of four-selection paths to the selected offspring. RESULTS: We developed a formula to predict the rate of inbreeding in populations undergoing four-path selection on genomically enhanced breeding values and with discrete generations. The new formula can be applied with or without selection. Neglecting the effects of selection led to underestimation of the rate of inbreeding by 40% to 45%. CONCLUSION: The formula we developed here would be highly useful as a practical method for predicting the approximate rate of inbreeding (ΔF) in populations where selection is performed according to four-path programs.
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The onset and worsening of some diseases are related to the variation and instability of gut microbiota. However, studies examining the personal variation of gut microbiota in detail are limited. Here, we evaluated the yearly variation of individual gut microbiota in 218 Japanese subjects aged 66-91 years, using Jensen-Shannon distance (JSD) metrics. Approximately 9% of the subjects showed a substantial change, as their formerly predominant bacterial families were replaced over the year. These subjects consumed fermented milk products less frequently than their peers. The relationship between the intake frequencies of fermented milk products containing Lactocaseibacillus paracasei strain Shirota (LcS) and JSD values was also investigated. The intra-individual JSD of subjects ingesting LcS products ≥ 3 days/week over the past 10 years was statistically lower than the < 3 days/week group (P = 0.045). Focusing on subjects with substantial gut microbiota changes, only 1.7% of the subjects were included in the LcS intake ≥ 3 days/week group whereas 11.3% were found in the < 3 days/week group (P = 0.029). These results suggest that about one-tenth of the elderly Japanese could experience a substantial change in their gut microbiota during a 1-year period, and that the habitual intake of probiotics may stabilize their gut microbiota.
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Microbioma Gastrointestinal , Lactobacillus/fisiologia , Idoso , Produtos Fermentados do Leite/microbiologia , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
Acclimation to high temperature increases plants' tolerance of subsequent lethal high temperatures. Although epigenetic regulation of plant gene expression is well studied, how plants maintain a memory of environmental changes over time remains unclear. Here, we show that JUMONJI (JMJ) proteins, demethylases involved in histone H3 lysine 27 trimethylation (H3K27me3), are necessary for Arabidopsis thaliana heat acclimation. Acclimation induces sustained H3K27me3 demethylation at HEAT SHOCK PROTEIN22 (HSP22) and HSP17.6C loci by JMJs, poising the HSP genes for subsequent activation. Upon sensing heat after a 3-day interval, JMJs directly reactivate these HSP genes. Finally, jmj mutants fail to maintain heat memory under fluctuating field temperature conditions. Our findings of an epigenetic memory mechanism involving histone demethylases may have implications for environmental adaptation of field plants.
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Arabidopsis/fisiologia , Proteínas de Choque Térmico/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Termotolerância/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Desmetilação , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Metilação , MutaçãoRESUMO
Epidemiological and clinical studies have suggested that ß-cryptoxanthin (ß-CX) has health benefits in humans. To understand the health benefits of ß-CX, it is important to examine its in vivo kinetics and identify a convenient noninvasive biomarker for serum ß-CX level. However, to date, there have been few studies of ß-CX kinetics in humans. We hypothesized that simultaneous consumption of fat-containing food would stimulate absorption of ß-CX. We conducted 2 in vivo kinetics studies, one after a single intake and the other after daily intake of ß-CX in healthy adults, to examine whether simultaneous consumption of fat-containing food stimulates absorption of ß-CX and whether palmar b* value (yellowness) is a suitable biomarker. After a single intake of 1.1 or 2.2â¯mg of ß-CX, the serum level increased dose-dependently and returned to the baseline level after 14 to 17â¯days. The simultaneous consumption of fat-containing food enhanced the absorption of ß-CX by 1.8-fold. During daily intake of 2.0â¯mg/day ß-CX with fat-containing food for 12â¯weeks, both serum ß-CX level and palmar b* value measured with a colorimeter increased continuously. After intake was halted, both serum ß-CX level and palmar b* value decreased. There was a positive correlation between serum ß-CX level and palmar b* value during the trial (Râ¯=â¯0.55, Pâ¯<â¯.001). These results suggest that intake of ß-CX with fat-containing food stimulates the absorption of ß-CX and increases palmar yellowness.
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beta-Criptoxantina/administração & dosagem , beta-Criptoxantina/sangue , Dieta/métodos , Gorduras na Dieta/administração & dosagem , Pigmentação da Pele/efeitos dos fármacos , Adulto , Disponibilidade Biológica , Biomarcadores/sangue , Carotenoides , Estudos Cross-Over , Feminino , Mãos , Humanos , Japão , Masculino , Valores de Referência , XantofilasRESUMO
Study of arsenic (As) provides guidelines for the development of next-generation materials. We clarify the unique structure of the third crystalline polymorph of natural As (Pnm21-As) by crystallographical experiment and the electronic structure by first-principles computational method. The crystal structure of Pnm21-As is a novel structure in which the basic portions of semi-metalic grey-As and semi-conductor black-As are alternately arranged at the atomic level. For both covalent and van der Waals bonding, the contributions of sd and pd hybridizations are important. Van der Waals bonding characteristics and d orbital contributions can be varied by control of layer stacking. Total charges are clearly divided into positive and negative in the same elements for the grey-As and black-As portions, respectively, is of importance. The sequence in which one-dimensional electron donor and acceptor portions alternate in the layer will be the first description.
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Infrequent bowel movements decrease the number of beneficial bacteria in the human intestines, thereby potentially increasing the individual's risk of colorectal cancer. The correction of such bowel problems could therefore make an important contribution to improving population health and quality-adjusted lifespan. We examined independent and interactive effects upon the fecal microbiota of two potentially favorable determinants of intestinal motility: the intake frequency of a fermented milk product containing Lactobacillus casei strain Shirota (LcS) and the quantity/quality of habitual physical activity in 338 community-living Japanese aged 65-92 years. Subjects were arbitrarily grouped on the basis of questionnaire estimates of LcS intake (0-2, 3-5, and 6-7 days/week) and pedometer/accelerometer-determined patterns of physical activity [<7000 and ≥7000 steps/day, or <15 and ≥15 min/day of activity at an intensity >3 metabolic equivalents (METs)]. After adjustment for potential confounders, the respective numbers of various beneficial fecal bacteria tended to be larger in more frequent consumers of LcS-containing products, this trend being statistically significant (mostly P < 0.001) for total Lactobacillus, the Lactobacillus casei subgroup, and the Atopobium cluster; in contrast, there were no statistically significant differences in fecal bacterial counts between the physical activity groups. A multivariate-adjusted logistic regression analysis estimated that the risk of infrequent bowel movements (arbitrarily defined as defecating ≤3 days/week) was significantly lower (P < 0.05) in subjects who ingested LcS-containing products 6-7 rather than 0-2 days/week [odds ratio (95% confidence interval) 0.382 (0.149-0.974)] and was also lower in those who took ≥7000 rather than <7000 steps/day [0.441 (0.201-0.971)] or spent ≥15 rather than <15 min/day of physical activity at an intensity >3 METs [0.412 (0.183-0.929)]. The risk of infrequent bowel movements in subjects who combined 6-7 days/week of LcS with ≥7000 steps/day or ≥15 min/day of activity at >3 METs was only a tenth of that for individuals who combined 0-2 days/week of LcS with <7000 steps/day or <15 min/day at >3 METs. These results suggest that elderly individuals can usefully ingest LcS-containing supplements regularly (≥6 days/week) and also engage in moderate habitual physical activity (≥7000 steps/day and/or ≥15 min/day at >3 METs) in order to enhance their gastrointestinal health.
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Glycation, a non-enzymatic glycosylation of proteins, induces tissue damage in association with various diseases and aging phenomena. Pentosidine, an advanced glycation end product, is involved in aging phenomena such as tissue stiffness. In this study, we aimed to find a potent anti-glycation food material and to verify its health benefits by clinical trial. From among 681 hot water plant extracts, lemon balm (Melissa officinalis; LB) leaf extract was selected and revealed to have more potent inhibitory activity for pentosidine formation than a representative anti-glycation agent, aminoguanidine. Rosmarinic acid (RA), a typical polyphenol in Lamiaceae plants, was identified as a major active component in LB extract (LBE). Furthermore, LBE or RA dose-dependently suppressed glycation-associated reactions such as increased fluorescence, yellowing of collagen fiber sheets, and degeneration of the fibrous structure of elastin fiber sheets. An open-label, parallel-group comparative trial was conducted in 28 healthy Japanese subjects aged 31-65 y who consumed LB tea (LB group) or barley tea (Control group) for 6 wk. The LB group showed significant reductions in brachial-ankle pulse wave velocity, reflecting arterial stiffness, and b* (yellow) color values in forearm skin compared with the Control group. A gender-stratified analysis revealed that cheek skin elasticity was significantly improved in the LB group compared with the Control group only in female subjects. It is concluded that the hot water extract of LB leaf has the potential to provide health benefits with regard to glycation-associated tissue damage in blood vessels and skin of healthy adults.
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Glicosilação/efeitos dos fármacos , Melissa/química , Extratos Vegetais/farmacologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Adulto , Proteínas de Arabidopsis/química , Bebidas , Cinamatos/farmacologia , Depsídeos/farmacologia , Dieta , Elasticidade , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/química , Fitoterapia , Extratos Vegetais/administração & dosagem , Ácido RosmarínicoRESUMO
PURPOSE: To analyze the retinal nerve fiber layer thickness(NFLT) as measured by optical coherence tomography(OCT) in glaucomatous eyes with hemifield defect and to evaluate the most effective parameter for the diagnosis of glaucoma with OCT. METHODS: One hundred eighty four(184) normal eyes(128 subjects) and 108 open-angle glaucomatous eyes(87 subjects) with superior or inferior hemifield defects verified by Humphrey field analyzer(HFA) were measured for NFLT with OCT. The correlations between NFLT and mean deviation on HFA were calculated. In combination with normal eye data, receiver operating characteristic curve(ROC curve) and AUC(area under the curve) of each NFLT in the affected hemifield were evaluated for the diagnosis of glaucoma. RESULTS: NFLT in both affected and unaffected hemifields was significantly correlated with mean deviation in HFA. An average of four 30 degrees segments close to the temporal side in the affected hemifield (parameter A120) had the highest correlation(r = 0.571) and the highest AUC(0.948) among all parameters. CONCLUSIONS: NFLT in the unaffected visual field decreases with the progression of glaucomatous damage. We suggest that the parameter A120 is the best indication in a diagnosis of glaucoma when measuring NFLT by OCT.
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Glaucoma/diagnóstico , Glaucoma/patologia , Fibras Nervosas/patologia , Retina/patologia , Tomografia de Coerência Óptica , Adulto , Idoso , Glaucoma/fisiopatologia , Humanos , Pessoa de Meia-Idade , Curva ROC , Campos VisuaisRESUMO
In our previous study, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in Apc(1309) mice at doses of 100 and 200 ppm in the diet. In contrast, it has been reported that doses of 1500 or 2000 ppm of another PPAR gamma agonist, troglitazone, enhanced colon polyp development in Min mice. In the present study, we therefore investigated the effects of a wide range of pioglitazone doses on both hyperlipidemia and intestinal polyp formation in Min mice. Serum triglycerides and very low density lipoprotein (VLDL) cholesterol in the basal diet group were elevated to levels 13-15 times higher than those in the wild-type counterparts at 20 weeks of age. They were reduced dose-dependently by treatment with 100, 200, 400 and 1600 ppm pioglitazone from 6-20 weeks of age with suppression to almost the wild-type level at the highest dose. Moreover, up-regulation of the liver mRNA levels for lipoprotein lipase (LPL) was evident in the pioglitazone-treated animals. Dose-dependent reduction of intestinal polyps was observed in Min mice given 100-1600 ppm for 14 weeks, total numbers being decreased to 63-9% of the control value. A suppressive effect of pioglitazone on colon polyp formation was also found. The PPAR gamma agonist, pioglitazone, may thus be a promising candidate chemopreventive agent for colon cancer.
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Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Polipose Intestinal/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/agonistas , Tiazolidinedionas/uso terapêutico , Fatores de Transcrição/agonistas , Animais , LDL-Colesterol/sangue , LDL-Colesterol/genética , Pólipos do Colo/sangue , Pólipos do Colo/tratamento farmacológico , Pólipos do Colo/patologia , Relação Dose-Resposta a Droga , Genes APC , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Polipose Intestinal/sangue , Polipose Intestinal/patologia , Ligantes , Lipase Lipoproteica/metabolismo , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pioglitazona , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Triglicerídeos/sangueRESUMO
Mongolian gerbils are considered to be a good animal model for understanding the development of Helicobacter pylori-associated diseases. However, limitations regarding the genetic information available for this animal species hamper the elucidation of underlying mechanisms. Thus, we have focused on identifying the nucleotide sequences of cDNAs encoding Mongolian gerbil inflammatory proteins, such as interleukin-1 (IL-1beta), tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, we examined the mRNA expression of these genes in the glandular stomach by RT-PCR at 1-8 weeks after H. pylori infection. The deduced amino acid homologies to mouse, rat and human proteins were 86.2%, 83.6% and 67.8% for IL-1beta, 87.2%, 85.1% and 78.4% for TNF-alpha , 91.9%, 90.2% and 84.8% for COX-2 and 90.8%, 89.1% and 80.1% for iNOS, respectively. The average stomach weight of Mongolian gerbils inoculated with H. pylori was increased in a time-dependent manner at 1, 2, 4 and 8 weeks after inoculation. In the pyloric region, mRNA expression levels of IL-1beta, TNF-alpha and iNOS were increased in H. pylori-infected animals at the 2 weeks time point, while in the fundic region, expression levels of IL-1beta, TNF-alpha and iNOS were elevated at 4 and 8 weeks. The COX-2 expression level in the fundic region was clearly elevated in infected animals compared with control animals at 4 and 8 weeks, but in the pyloric region, expression levels were similar in both infected and control animals. Thus, our results indicate that oxidative stress occurs from an early stage of H. pylori infection in the glandular stomach of Mongolian gerbils.
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Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Isoenzimas/metabolismo , Proteínas Inflamatórias de Macrófagos/metabolismo , Óxido Nítrico Sintase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Clonagem Molecular , Ciclo-Oxigenase 2 , DNA Complementar , Gastrite/metabolismo , Gastrite/microbiologia , Gerbillinae , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Interleucina-1/metabolismo , Interleucina-1beta , Óxido Nítrico Sintase Tipo II , Tamanho do Órgão , Fragmentos de Peptídeos/metabolismo , Estômago/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Since urease of Helicobacter pylori is essential for its colonization, we focused attention on foodstuffs which inhibit the activity of this enzyme. Among plant-derived 77 foodstuff samples tested, some tea and rosemary extracts were found to clearly inhibit H. pylori urease in vitro. In particular, green tea extract (GTE) showed the strongest inhibition of H. pylori urease, with an IC(50) value of 13 microg/ml. Active principles were identified to be catechins, the hydroxyl group of 5(')-position appearing important for urease inhibition. Furthermore, when H. pylori-inoculated Mongolian gerbils were given GTE in drinking water at the concentrations of 500, 1000, and 2000 ppm for 6 weeks, gastritis and the prevalence of H. pylori-infected animals were suppressed in a dose-dependent manner. Since the acquisition by H. pylori of resistance to antibiotics has become a serious problem, tea and tea catechins may be very safe resources to control H. pylori-associated gastroduodenal diseases.