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TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channels.

I(Ks), a slowly activating delayed rectifier K(+) current through channels formed by the assembly of two subunits KCNQ1 (KvLQT1) and KCNE1 (minK), contributes to the control of the cardiac action potential duration. Coassembly of the two subunits is essential in producing the characteristic and physiologically critical kinetics of assembled channels, but it is not yet clear where or how these subunits interact. Previous investigations of external access to the KCNE1 protein in assembled I(Ks) channels relied on occlusion of the pore by extracellular application of TEA(+), despite the very low TEA(+) sensitivity (estimated EC(50) > 100 mM) of channels encoded by coassembly of wild-type KCNQ1 with the wild type (WT) or a series of cysteine-mutated KCNE1 constructs. We have engineered a high affinity TEA(+) binding site into the h-KCNQ1 channel by either a single (V319Y) or double (K318I, V319Y) mutation, and retested it for pore-delimited access to specific sites on coassembled KCNE1 subunits. Coexpression of either KCNQ1 construct with WT KCNE1 in Chinese hamster ovary cells does not alter the TEA(+) sensitivity of the homomeric channels (IC(50) approximately 0.4 mM [TEA(+)](out)), providing evidence that KCNE1 coassembly does not markedly alter the structure of the outer pore of the KCNQ1 channel. Coexpression of a cysteine-substituted KCNE1 (F54C) with V319Y significantly increases the sensitivity of channels to external Cd(2+), but neither the extent of nor the kinetics of the onset of (or the recovery from) Cd(2+) block was affected by [TEA(+)](o) at 10x the IC(50) for channel block. These data strongly suggest that access of Cd(2+) to the cysteine-mutated site on KCNE1 is independent of pore occlusion caused by TEA(+) binding to the outer region of the KCNE1/V319Y pore, and that KCNE1 does not reside within the pore region of the assembled channels.

Action Potentials↗

A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.

Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an aromatic amino acid at a position that sits at the external entrance of the permeation pathway (residue 449 in the eukaryotic voltage-gated potassium channel Shaker). We investigated whether a cation-pi interaction between TEA and such an aromatic residue contributes to TEA block using the in vivo nonsense suppression method to incorporate a series of increasingly fluorinated Phe side chains at position 449. Fluorination, which is known to decrease the cation-pi binding ability of an aromatic ring, progressively increased the inhibitory constant K(i) for the TEA block of Shaker. A larger increase in K(i) was observed when the benzene ring of Phe449 was substituted by nonaromatic cyclohexane. These results support a strong cation-pi component to the TEA block. The data provide an empirical basis for choosing between Shaker models that are based on two classes of reported crystal structures for the bacterial channel KcsA, showing residue Tyr82 in orientations either compatible or incompatible with a cation-pi mechanism. We propose that the aromatic residue at this position in Shaker is favorably oriented for a cation-pi interaction with the permeation pathway. This choice is supported by high level ab initio calculations of the predicted effects of Phe modifications on TEA binding energy.

Amino Acid Sequence↗

Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity.

Teas represent a large family of plants containing high amounts of polyphenols that may confer health benefits in various diseases. Recently, it has been hypothesized that tea consumption may also reduce the risk of age-related neurodegenerative pathologies. Considering the deleterious role of beta-amyloid (Abeta) in the aetiology of Alzheimer's disease (AD), we investigated green and black tea extracts and flavan-3-ols (present as monomers and dimers in green and black forms, respectively) against toxicity induced by Abeta-derived peptides using primary cultures of rat hippocampal cells as model. Both green and black tea extracts (5-25 microg/mL) displayed neuroprotective action against Abeta toxicity. These effects were shared by gallic acid (1-20 microm), epicatechin gallate (ECG; 1-20 microM) and epigallocatechin gallate (EGCG; 1-10 microM), the former being the most potent flavan-3-ol. In contrast, epicatechin and epigallocatechin were ineffective in the same range of concentrations. Moreover, only tea flavan-3-ol gallate esters (i.e. ECG, EGCG) and gallic acid inhibited apoptotic events induced by Abeta(25-35). Interestingly, EGCG and gallic acid inhibited Abeta aggregation and/or the formation of Abeta-derived diffusible neurotoxin ligands. Taken together, these results indicate that the catechin gallates (through the galloyl moiety) contribute to the neuroprotective effects of both green and black teas. Moreover, the protective effect of EGCG is likely to be associated, at least in part, with its inhibitory action on Abeta fibrils/oligomers formation. These data also support the hypothesis that not only green but also black teas may reduce age-related neurodegenerative diseases, such as AD.

Amyloid beta-Peptides↗

Antibacterial effect of crude water-soluble arrowroot (Puerariae radix) tea extracts on food-borne pathogens in liquid medium.

AIMS: To evaluate the effect of crude water-soluble arrowroot tea extracts on microbial growth of food-borne pathogens in liquid medium and to confirm the damage to bacterial cells using Transmission Electronic Microscopy (TEM). METHODS AND RESULTS: Inhibition of growth of Escherichia coli O157:H7, Salmonella enterica serovar Enteritidis, Listeria monocytogenes and Staphylococcus aureus was investigated using Brain Heart Infusion (BHI) broth containing 0 (control), 0.63, 1.25, 2.5 and 5.0% (w/v) arrowroot tea. Bacterial cell counts were performed on specific selective agar on days 0, 1, 3 and 5. BHI containing 5.0% arrowroot tea extract showed a 6-7 log suppression of growth for all test strains on days 3 and 5, compared with the control. Even 0.63% arrowroot tea effectively inhibited microbial growth of all test strains on day 5. TEM images of the samples treated with 5.0% arrowroot tea revealed the rupture of cell walls and nonhomogeneous disposition of cytoplasmic materials within treated bacteria. CONCLUSIONS: Crude water-soluble arrowroot tea extract strongly inhibited microbial growth of all test pathogens in liquid medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Water-soluble arrowroot tea extract has the potential to be used directly on foods or as a spray on the surfaces of food handling and processing facilities in order to prevent microbial growth of both Gram-negative and Gram-positive bacteria.

Anti-Bacterial Agents↗

TEA- and apamin-resistant K(Ca) channels in guinea-pig myenteric neurons: slow AHP channels.

The patch-clamp technique was used to record from intact ganglia of the guinea-pig duodenum in order to characterize the K(+) channels that underlie the slow afterhyperpolarization (slow AHP) of myenteric neurons. Cell-attached patch recordings from slow AHP-generating (AH) neurons revealed an increased open probability (P(o)) of TEA-resistant K(+) channels following action potentials. The P(o) increased from < 0.06 before action potentials to 0.33 in the 2 s following action potential firing. The ensemble averaged current had a similar time course to the current underlying the slow AHP. TEA- and apamin-resistant Ca(2+)-activated K(+) (K(Ca)) channels were present in inside-out patches excised from AH neurons. The P(o) of these channels increased from < 0.03 to approximately 0.5 upon increasing cytoplasmic [Ca(2+)] from < 10 nM to either 500 nM or 10 microM. P(o) was insensitive to changes in transpatch potential. The unitary conductance of these TEA- and apamin-resistant K(Ca) channels measured approximately 60 pS under symmetric K(+) concentrations between -60 mV and +60 mV, but decreased outside this range. Under asymmetrical [K(+)], the open channel current showed outward rectification and had a limiting slope conductance of about 40 pS. Activation of the TEA- and apamin-resistant K(Ca) channels by internal Ca(2+) in excised patches was not reversed by washing out the Ca(2+)-containing solution and replacing it with nominally Ca(2+)-free physiological solution. Kinetic analysis of the single channel recordings of the TEA- and apamin-resistant K(Ca) channels was consistent with their having a single open state of about 2 ms (open dwell time distribution was fitted with a single exponential) and at least two closed states (two exponential functions were required to adequately fit the closed dwell time distribution). The Ca(2+) dependence of the activation of TEA- and apamin-resistant K(Ca) channels resides in the long-lived closed state which decreased from > 100 ms in the absence of Ca(2+) to about 7 ms in the presence of submicromolar cytoplasmic Ca(2+). The Ca(2+)-insensitive closed dwell time had a time constant of about 1 ms. We propose that these small-to-intermediate conductance TEA- and apamin-resistant Ca(2+)-activated K(+) channels are the channels that are primarily responsible for the slow AHP in myenteric AH neurons.

Animals↗

5S rDNA gene diversity in tea (Camellia sinensis (L.) O. Kuntze) and its use for variety identification.

Variability in the organization of repeats of 5S rDNA is useful for phylogenetic studies in various crops. We found variable repeats of 5S rDNA gene in the genome of tea (Camellia sinensis (L.) O. Kuntze) during Southern hybridization. Variability in the repeats of 5S rDNA with specific restriction endonucleases (Sau3AI, BamHI, and ApoI) was analyzed in 28 different tea clones representing 3 types of tea. Our results clearly show that the 5S rDNA gene in tea could be used as a molecular marker to distinguish C. sinensis Chinary tea from the other important types of tea, namely Assamica and Cambod. Upon analysis with restriction endonucleases, the 5S rDNA gene in the tea genome was found to be heavily methylated.

Camellia sinensis↗

Internal and external TEA block in single cloned K+ channels.

Tetraethylammonium (TEA) has been used recently to probe natural and mutational variants of voltage-dependent K+ channels encoded by cDNA clones. Its usefulness as a probe of channel structure prompted us to examine the molecular mechanism by which TEA blocks single-channel currents in Xenopus oocytes expressing the rat brain K+ channel, RCK2. TEA at the intracellular surface of membrane patches decreased channel open time and increased the duration of closed intervals. Tetrapentylammonium had similar but more potent effects. Extracellular application of TEA caused an apparent reduction of single-channel amplitude. Block was slower at the high-affinity internal site than at the low-affinity external site. Internal TEA selectively blocks open K+ channels, and the voltage dependence of the block indicates that the binding site lies within the membrane electric field at a point 25% of the distance from the cytoplasmic margin. External TEA also interacts with the open channel but is less sensitive to membrane potential. The results indicate that the internal and external TEA binding sites define the inner and outer margins of the aqueous pore.

Animals↗

MPP+ is transported by the TEA(+)-H+ exchanger of renal brush-border membrane vesicles.

Rabbit renal brush-border membrane vesicles (BBMV) were used to study the transport of the cationic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). An outwardly directed H(+)-gradient stimulated MPP+ uptake and led to the development of an active accumulation of MPP+ within the vesicles. H(+)-gradient driven MPP+ transport was saturable, with a maximal transport rate of 3 nmol.mg-1.min-1 and an apparent Michaelis constant (Kt) of 8 microM. MPP+ and tetraethylammonium (TEA) behaved as competitive inhibitors of one another's transport in renal BBMV, suggesting the presence of a common transport pathway for these organic cations. At an ambient pH of 7.5, preloading BBMV with MPP+ failed to stimulate TEA uptake, although trans TEA did stimulate MPP+ uptake. Increasing ambient pH to 8.5 (i.e., reducing competition between H+ and these organic cations for a common transport pathway) led to a clear reciprocal trans stimulation of TEA and MPP+ fluxes. With an equilibrium-shift protocol, a trans concentration of MPP+ energized uphill transport of TEA. We conclude that MPP+ and TEA share a common organic cation-H+ exchange pathway in the renal brush border, although turnover of an MPP(+)-loaded exchanger is slow compared with that for a TEA or H(+)-loaded exchanger.

1-Methyl-4-phenylpyridinium↗

The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults.

BACKGROUND: In western populations, coffee consumption is associated with a reduced risk for type 2 diabetes; however, the effect of green, black, and oolong teas is unclear. OBJECTIVE: To examine the relationship between consumption of these beverages and risk for diabetes. DESIGN: Retrospective cohort study. SETTING: 25 communities across Japan. PARTICIPANTS: A total of 17,413 persons (6727 men and 10,686 women; 49% of the original study population) who were 40 to 65 years of age; had no history of type 2 diabetes, cardiovascular disease, or cancer at the baseline lifestyle survey; and completed the 5-year follow-up questionnaire. There was no difference in body mass index levels at baseline between respondents and nonrespondents. MEASUREMENTS: Questionnaire on consumption of coffee; black, green, and oolong teas; and physician-diagnosed diabetes. RESULTS: During the 5-year follow-up, there were 444 self-reported new cases of diabetes in 231 men and 213 women (5-year event rates, 3.4% and 2.0%, respectively). Consumption of green tea and coffee was inversely associated with risk for diabetes after adjustment for age, sex, body mass index, and other risk factors. Multivariable odds ratios for diabetes among participants who frequently drank green tea and coffee (> or =6 cups of green tea per day and > or =3 cups of coffee per day) were 0.67 (95% CI, 0.47 to 0.94) and 0.58 (CI, 0.37 to 0.90), respectively, compared with those who drank less than 1 cup per week. No association was found between consumption of black or oolong teas and the risk for diabetes. Total caffeine intake from these beverages was associated with a 33% reduced risk for diabetes. These inverse associations were more pronounced in women and in overweight men. LIMITATIONS: Diabetes was self-reported, no data were available on consumption of soda, and the follow-up rate was low. CONCLUSIONS: Consumption of green tea, coffee, and total caffeine was associated with a reduced risk for type 2 diabetes.

Adult↗

Inhibition of Cell Proliferation and Induction of Apoptosis During Azoxymethane Induced Colon Carcinogenesis by Black Tea.

Tea (Camellia sinensis) is one of the most popular beverages, consumed worldwide. The health promoting properties of tea have been attributed to its antioxidative polyphenolic constituents and their oxidative products. The aim of the present study was to evaluate the chemopreventive efficacy of a black tea infusion on azoxymethane induced colonic preneoplastic lesions, the aberrant crypt foci in Sprague-Dawley rats. Rats were injected with azoxymethane (15mg/kg.b.w.) and received oral administration of 1% and 2% (w/v) tea infusions from the 1(st)day of carcinogen application. The treatment was continued for 12 weeks. The colons were then assessed for aberrant crypt foci and compared with the untreated carcinogen control group. In situ cell proliferation and in situ apoptosis were also estimated using Brdu incorporation and the TUNEL method, respectively. Aberrant crypt foci were reduced significantly (by 44% in the 1% tea-treated and by about 40% in 2% tea-treated group). Significant decrease in proliferation and increase in apoptosis suggest a possible interplay between the two processes resulting in inhibition of colon carcinogenesis by black tea.

Journal Article↗

Thoracic epidural anesthesia (TEA) with 0.2% ropivacaine in combination with ipsilateral brachial plexus block (BPB) for modified radical mastectomy (MRM).

BACKGROUND: Breast cancer is the 2nd most common tumors in Thai women. Until now, oncologic breast surgeries are typically performed by general anesthesia (GA). However, GA cannot provide adequate postoperative pain control and routine use of parenteral opioids aggravate postoperative sedation, nausea, emesis, impaired oxygenation and depressed ventilation. Thoracic epidural anesthesia (TEA) is one of the regional anesthetic techniques that can be done by using a low dose of local anesthetic in combination with ipsilateral brachial plexus block (BPB) for axillary node dissection. TEA can provide a better pain relief without potential paralysis of respiratory muscle and sedation. MATERIAL AND METHOD: Fifty ASA PS I-III patients undergoing MRM were randomly assigned to two study groups of 25 patients each. In the TEA group, an epidural catheter was inserted at T4 to T5, and 10-15 ml of 0.2% ropivacaine was injected, then interscalene BPB was done with 8 ml of 0.2% ropivacaine. Anesthesia was maintained with 5-10 ml of 0.2% ropivacaine per hour. GA was induced with 1 microg/kg of fentanyl followed by 1.5-2 mg/kg of propofol and was maintained with sevoflurane and 70% N2O in oxygen. The authors evaluated the adequacy of anesthesia, surgical condition, postanesthetic recovery, postanesthetic analgesia and patients' satisfaction. RESULTS: The demographic data was similar in both groups. The number of patients immediately arrived at PACU with a sedation score of 1 was significantly greater in TEA group (p = 0.003) while the number of patients with an Aldrete score of 10 was greater but not statistically significant (p = 0.25). The verbal rating scale and analgesic requirement were significantly lower in the TEA group (p < 0.001 and p = 0.002 respectively). Patients' satisfaction was greater with TEA than with GA (p = 0.014). Surgical condition was similar in both groups. CONCLUSION: The present study shows that TEA combined with BPB by using a low dose of 0.2% ropivacaine is a safe and reliable alternative technique for MRM. It can provide not only effective anesthesia but also better postoperative pain relief faster anesthetic recovery and greater patient satisfaction than those of the GA technique.

Adult↗

Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP.

The role of voltage-dependent Ca2+ channels (VDCCs) in the induction of long-term potentiation (LTP) in the CA1 region of rat hippocampus was determined by examining the relationship between LTP and the long-lasting synaptic enhancement induced by extracellular application of tetraethylammonium (TEA). Consistent with previous findings (Aniksztejn and Ben-Ari, 1991), the TEA-induced synaptic enhancement did not require NMDA receptor activation. It was blocked by the L-type VDCC antagonist nifedipine or by intracellular injection of the Ca2+ chelator 1,2-bis(2-amino-phenoxy)ethane N,N,N',N'-tetra-acetic acid (BAPTA) and could be mimicked by direct activation of VDCCs with repetitive depolarizing current pulses. In contrast to its effect on TEA-induced synaptic enhancement, nifedipine had no effect on the magnitude or duration of NMDA receptor-dependent LTP. Saturation of NMDA receptor-dependent LTP reduced the magnitude of the TEA-induced synaptic enhancement. Similarly, increasing synaptic strength by initial application of TEA reduced the magnitude of the subsequent tetanus-induced LTP. Like LTP, the TEA-induced synaptic enhancement did not significantly affect paired-pulse facilitation. These results suggest that dihydropyridine-sensitive VDCCs do not normally contribute to the induction of NMDA receptor-dependent LTP even though their repetitive activation can generate an increase in synaptic strength. The mutual occlusion of LTP and TEA-induced synaptic enhancement suggests that they share a common expression mechanism and perhaps are generated by activation of common Ca(2+)-dependent intracellular processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Caries preventive effect of wild tea (tsaang-gubat) among school children.

A 3-year study was conducted to determine the effectiveness of wild tea (tsaang-gubat) as a caries preventive agent among schoolchildren in two elementary schools. The experimental group drank one cup of tea daily for 17 months. Tea drink was prepared by boiling for 30 minutes, fresh tea leaves from the school garden. Results showed that wild tea is an effective caries preventive agent. A significant decrease of 75.67% in caries incidence was observed highest in the mesial and occlusal surfaces. Increase in caries incidence in the third year was due to irregular drinking sessions and decrease in fluoride content of tea. Wild tea (tsaang-gubat) drink is acceptable to the pupils even with less sugar, costs cheap and is readily available.

Beverages↗

Influence of built environment on occupational health of women workers in tea plantations of India: a systematic review.

The built environment, comprising homes, buildings, roads, public spaces, infrastructure, land use, civic design, and amenities, has a considerable influence on occupational health. In India's tea plantations, where women comprise majority of the workforce, the built environment plays a crucial role in determining occupational health. The aforementioned point can be explained by the co-occurrence of living and working conditions, which often coexist in tea plantations, further resulting in vulnerabilities to the health of women workers. Therefore, to understand the influence of built environment on the occupational health of women workers in tea plantations of India, the present paper employs a systematic review using the PRISMA 2020 framework. In the first search, 421 studies were identified, of which 21 studies met all the inclusion criteria. A quality appraisal and risk of bias of the included studies have been undertaken. The results identified that musculoskeletal disorders (MSDs) are the most prevalent occupational health consequence, affecting over 80&#x202f;% of the women workers in Indian tea plantations, substantiated by a range of estimates in the studies reviewed. Gendered disparities in wage earning, self-autonomy, and dual responsibilities often lead to emotional distress, as delineated in minimal of the reviewed studies, grounded on self-disclosed or qualitative analysis. Further, deprived housing conditions and other facilities across the reviewed studies reflect institutional negligence. Therefore, by conducting a systematic synthesis of occupational health of women workers in the Indian tea plantation sector through the lens of the built environment, prior accounts have been extended. Addressing these issues is essential for safeguarding women workers, which will ensure the longevity of the Indian tea industry.

Female↗

Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study.

OBJECTIVE: To evaluate whether coffee, tea, and caffeine consumption are risk factors for rheumatoid arthritis (RA) onset among older women. METHODS: These factors were evaluated in a prospective cohort study that was initiated in 1986 and that included 31,336 women ages 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (95% CI) were used as the measures of association and were adjusted for age, alcohol use, smoking history, age at menopause, marital status, and the use of hormone replacement therapy. RESULTS: Compared with those reporting no use, subjects drinking > or =4 cups/day of decaffeinated coffee were at increased risk of RA (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA. Multivariable adjustment for a number of potential confounders did not alter these results. The associations of RA onset with the highest categories of decaffeinated coffee consumption (RR 3.10, 95% CI 1.75-5.48) and tea consumption (RR 0.24, 95% CI 0.06-0.98) were stronger in women with seropositive disease compared with those with seronegative disease (RR 1.54, 95% CI 0.62-3.84 and RR 0.93, 95% CI 0.27-3.20, respectively). CONCLUSION: Decaffeinated coffee intake is independently and positively associated with RA onset, while tea consumption shows an inverse association with disease onset. Further investigations of decaffeinated coffee and tea intake as arthritis risk factors are needed to verify these findings and explore their biologic basis.

Aged↗

Identification and determination of active anthraquinones in Chinese teas by micellar electrokinetic capillary chromatography.

The simultaneous determination of emodin, aloe-emodin and rhein, in Semen Cassiae, Qinghai Wild Dahuang tea, Ningxia Juemingzi tea, Lanzhou Juemingzi tea and Surong Juemingzi tea, has been investigated by micellar electrokinetic capillary chromatography for the fi rst time. With an electrolyte containing 15 mm borax, 30 mm SDS, 10% (v/v) ethanol, at pH 9.60 and 20 kV applied voltage, the three analytes were completely separated within 12 min. The effects of the concentration of borax, electrolyte pH, the concentrations of SDS and organic modifier and the applied voltage on electropheoretic behavior and separation were studied. The linear calibration range was 4-120 micro g/mL (r = 0.9921) for emodin, 10-200 micro g/mL (r = 0.9970) for aloe-emodin and 2-100 micro g/mL (r = 0.9971) for rhein, respectively. Under the optimum conditions, the relative standard deviation (RSD) values (n = 6) of the migration time and the peak area of each peak was 0.59-0.80% and 1.30-3.22%, respectively. The contents of the analytes in Rheum, Qinghai Wild Dahuang tea, Semen Cassiae and three other kinds of teas were easily determined with recoveries ranging from 95.3 to 104.4%.

Anthraquinones↗

Protective effect of green tea on the risks of chronic gastritis and stomach cancer.

Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack-years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95% CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose-response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre-malignant lesions in the high-risk population.

Adult↗

Prostate carcinoma and green tea: (-)epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine TRAMP model.

Green tea infusion has been shown to inhibit metastatic spreading of the transgenic adenocarcinoma of mouse prostate (TRAMP). Investigation on the molecular mechanisms triggered by the main green tea flavonoid, (-)epigallocatechin-3-gallate (EGCG), shows that EGCG restrains TRAMP-C1 cell proliferation in a dose-dependent manner, at concentrations (IC(50) < 0.2 microM) equivalent to those measured in the plasma of moderate green-tea drinkers. Up to 10 microM, EGCG does not modify the cell-surface immuno-localization of MMP-2, one of the invasion-instrumental proteinases; but while in default culture conditions these cells secrete mainly pro-MMP-2, in the presence of reconstituted basement membrane (Matrigel) they release almost exclusively pro-MMP-9. In contrast, when stimulated to traverse Matrigel toward a chemo-attractant, in addition to pro-MMP-9, they secrete pro-MMP-2. In the presence of 0.2 microM EGCG, only the level of the latter is markedly lowered in the conditioned medium, in parallel with the invasive behavior (>50%). In vivo, s.c. injection of TRAMP-C1 cells dispersed in Matrigel gives origin to a tumor mass, whose growth is not inhibited by green-tea regimen. This growth is contained greater than two-thirds by LPS-triggered polymorpho-nuclear phagocyte (PMN) recruitment but this effect is abolished by green tea. Nevertheless, while tumor-released pro-MMP-2 is activated by co-incubation of TRAMP-C1 cells with PMNs, in the presence of 10 microM EGCG the activation is almost abolished. These results suggest that inflammatory involvement of prostate carcinoma could be efficaciously prevented by green tea with a concomitant lowering of the invasive potential.

Adenocarcinoma↗