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ABSTRACT: Limited beta-lactams show antipseudomonal activity. The rapid spread of IMP-type metallo-beta-lactamases (MBLs), which have a broad spectrum of substrates and a poor susceptibility to clinically available inhibitors, further restricts beta-lactam use. In the present study, we evaluated the potency of IMP-10 MBL in hydrolysing antipseudomonal beta-lactams currently available in the clinic. Crude IMP-10 MBL was prepared from two clinical isolates of Pseudomonas aeruginosa harbouring the bla(IMP-10) gene. The sensitivity of beta-lactams to hydrolysis by IMP-10 MBL was determined by comparing the MICs of 14 antipseudomonal beta-lactams against a susceptible strain of P. aeruginosa in the presence and absence of IMP-10 MBL. Carbapenems (imipenem, meropenem and panipenem) and extended-spectrum cephems (ceftazidime, cefoperazone, cefsulodin and cefepime) were sensitive to the hydrolysing activity of IMP-10 MBL. By comparison, the fourth-generation cephem (cefpirome), the extended-spectrum penicillins (carbenicillin, ticarcillin, piperacillin and mezlocillin) and monobactams (aztreonam and carumonam) were relatively resistant to IMP-10 MBL. The sensitivity profile of antipseudomonal beta-lactams to IMP-10 MBL generated in the present study provides a valuable reference for antibiotic selection by medical professionals.
Journal of Medical Microbiology 08/2008; 57(Pt 8):974-9. · 2.50 Impact Factor
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ABSTRACT: Extracts of black tea inhibited the infectivity of influenza virus A and influenza virus B for Madin-Darby Canine Kidney cells. Tea extract inhibited virus adsorption to the cells but did not inhibit virus replication in the cells.
Letters in Applied Microbiology 06/2008; 11(1):38 - 40. · 1.62 Impact Factor
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ABSTRACT: Extracts of black tea, green tea, pu-erh tea or coffee inhibited the growth of various bacteria known to cause diarrhoeal diseases. Tea or coffee also showed bactericidal activity against Staphylococcus aureus and Vibrio parahaemolyticus.
Letters in Applied Microbiology 03/2008; 8(4):123 - 125. · 1.62 Impact Factor
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ABSTRACT: Extracts of tea and coffee inhibited the haemolytic activities of Staphylococcus aureusα-toxin and Vibrio parahaemolyticus thermostable direct haemolysin (Vp-TDH). Black tea had the strongest anti-haemolysin activity. Green tea was more active than pu-erh tea. Coffee had anti-Vp-TDH activity but not anti-α-toxin activity.
Letters in Applied Microbiology 03/2008; 9(2):65 - 66. · 1.62 Impact Factor
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ABSTRACT: Epigallocatechin gallate (EGCg), the major tea catechin, is known as a potent anti-microbial and anti-tumor compound. The effects of EGCg on host defense mechanisms against Listeria monocytogenes infection were examined in vitro using mouse peritoneal exudate cells. The study showed that EGCg inhibited the intracellular growth of L. monocytogenes in macrophages. The enhancement of in vitro anti-L. monocytogenes activity by EGCg is not due to the modulation of reactive oxygen intermediates or the production of reactive nitrogen intermediates but due to the inhibition of its escaping from the phagosome into cytosolic space. Anti-L. monocytogenes of EGCg is through the inhibition of hemolytic and cholesterol-binding activity of listeriolysin O, which usually disrupts the phagosomal membrane in the escaping phase of L. monocytogenes.
Biochemical and Biophysical Research Communications 02/2008; 365(2):310-5. · 2.48 Impact Factor
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ABSTRACT: Some clinical isolates of Serratia marcescens showed high-level resistance to expanded-spectrum cephalosporins alone and in combination with beta-lactamase inhibitor, but the beta-lactamase extracted from these strains was sensitive to the inhibitors. This study examines the possible mechanisms responsible for the discrepancy.
Three clinical isolates of S. marcescens bore the bla(TEM) gene coded on a plasmid. This was confirmed by detection of the bla gene using PCR analysis and by transferring resistance determinants to Escherichia coli via conjugation and transformation. All of the E. coli transconjugants and transformants acquired a similar level of resistance to penicillins and narrow-spectrum cephalosporins, and showed the reduced susceptibility to expanded-spectrum cephalosporins alone and in combination with clavulanate. As a result of the highly constitutive expression of the TEM gene, up to 247-690 U of beta-lactamase were produced by 10(10) cells of wild-type S. marcescens and the transconjugants and transformants. In the presence of 0.24 U/ml of TEM enzyme, the minimum inhibition concentrations of cefotaxime against E. coli ATCC 25922 increased from 0.125 to 512 microg/ml. The TEM-type beta-lactamase extracted from these strains was sensitive to clavulanate, and 62.2-92.1% of its activity was inhibited after preincubation with 0.1 mM clavulanate.
The TEM-type beta-lactamase plays a critical role in the resistance of S. marcescens to beta-lactams, and the hyperproduction of inhibitor-susceptible TEM beta-lactamase is responsible for the resistance to beta-lactam-beta-lactamase inhibitor combinations.
Chemotherapy 02/2008; 54(1):31-7. · 1.82 Impact Factor
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ABSTRACT: Catechin, a constituent of tea, possesses various bioactivities. In particular, the most abundant catechin in tea is epigallocatechin gallate (EGCg), which has an anti-inflammatory effect. In the present study, the usability of EGCg for osteomyelitis treatment was examined. Osteomyelitis is a difficult disease to cure, partly due to bone lysis caused by infected osteoblasts. Since bone lysis is promoted by proinflammatory cytokines and the receptor activator of NF-kappaB ligand (RANKL), osteoblasts were infected with Staphylococcus aureus and the effect of EGCg on the production of cytokines was examined. It was found that the production of interleukin 6 and RANKL was suppressed in the osteoblasts treated with EGCg, which indicated an inflammation suppression effect of EGCg in osteomyelitis treatment.
Journal of Medical Microbiology 09/2007; 56(Pt 8):1042-6. · 2.50 Impact Factor
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ABSTRACT: Given the absence of recent reports on the isolation rate of Serratia marcescens by pili type, clinical isolates from respiratory and urinary tract specimens--prime loci of infection by this organism--were subjected to examination. The 123 S. marcescens strains (serotype O2, 67 strains, serotype O14, 56 strains) used in this study were isolated from inpatients at Showa University Fujigaoka Hospital during the 5 years from April 1997 to March 2002. Higher rates of S. marcescens O2 with mannose-resistant (MR)/K Klebsiella-like pili were detected among the respiratory tract-derived strains. On the other hand, more non-hemagglutinating O14 strains were found among the urinary tract-derived strains. Analysis by study phase revealed a rise in the isolation rate of non-hemagglutinating strains, from 0-17.4% for O2 strains and 34.5%-66.7% for O14 strains, between phase I (April 1997 to March 1999) and phase II (April 1999 to March 2002) of the study. In order to examine the increasing non-hemagglutinating strains in detail, the 28 serotype O14 non-hemagglutinating strains, and 8 strains with only mannose-sensitive (MS) pili were subjected to genotyping by pulsed-field gel electrophoresis (PFGE), revealing the presence of 10 clones with disparate genotypes. The A1 strain isolated at the highest frequency was non-hemagglutinating in all cases and possessed the same genotype, indicating proliferation within the hospital over the 5 years of the study. These results indicate that non-hemagglutinating strains were transmitted among patients within the hospital.
Journal of Infection and Chemotherapy 07/2007; 13(3):151-6. · 1.80 Impact Factor
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ABSTRACT: To evaluate the roles of blaIMP and blaTEM genes in the resistance of Serratia marcescens against beta-lactams and to find the spreading ways of these genes, 19 clinical isolates of imipenem-resistant Serratia marcescens were analyzed. Six strains bore blaIMP and blaTEM genes on a single plasmid, as confirmed by transferring resistance determinants via conjugation and transformation, and by detecting bla genes with PCR analysis. The six strains showed two different genomic patterns on pulsed-field gel electrophoresis. All the transconjugants and transformants gained high-level resistance to ampicillin, cephalexin, cefoxitin and cefotaxime, and showed a reduced susceptibility to imipenem, but maintained full susceptibility to aztreonam. In addition, the expressions of blaIMP and blaTEM genes were constitutive, either in Serratia marcescens clinical isolates or in their transconjugants and transformants. These findings may explain the rapid spread of the above resistance determinants among Enterobacteriaceae via transmissible plasmids in the clinical setting.
Microbiological Research 02/2007; 162(1):46-52. · 2.31 Impact Factor
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ABSTRACT: Mast cells are potent effectors playing a key role in IgE-associated hypersensitivity reactions, allergic disorders, inflammation and protective immune responses. Mast cell development in vivo occurs mainly in non-hematopoietic microenvironments and increased mast cell numbers can be seen in various inflammatory diseases and pathologic conditions. SCF (also known as kit ligand or KitL) and c-kit signaling are essential for both human and murine mast cell development, while IL-3 is required for murine mast cell hyperplasia that occurs in response to various stimuli. Besides SCF and IL-3, the cytokines IL-4, IL-9, IL-10 and IL-13 are also called mast cell growth factors due to their actions synergistically promoting mast cell proliferation and differentiation in the presence of SCF or IL-3. These cytokines alone however are unable to support neither the proliferation nor survival of mast cells. Most research has focused on examining the direct effects of the above cytokines on mast cells or their precursors. However, it is difficult to explain the process of mast cell development only in terms of the above mast cell growth factors. A series of experiments in our laboratory and by others has revealed that inflammatory mediators and cytokines, as triggers or regulators, are also crucial for mast cell development. This review summarizes recent progress in our understanding of how various inflammatory factors regulate mast cell development, with particular focus on the effects of prostaglandin E (PGE), TNF-alpha, IL-6, IFN-gamma and an unknown apoptosis-inducing factor produced by IL-4-stimulated macrophages.
Current Medicinal Chemistry 02/2007; 14(28):3044-50. · 4.86 Impact Factor
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ABSTRACT: “Drinking several cups of green tea a day keeps the doctor away” is clearly an overstatement. However, extensive research has revealed that the predominant catechin from tea (Camellia sinensis), epigallocatechin gallate (EGCg), has significant medicinal and health-promoting properties. This review summarizes what is presently known about the antimicrobial properties of EGCg, with a particular focus on the synergistic relationship between EGCg and β-lactams in the inhibition of methicillin-resistant Staphylococcus aureus (MRSA). The mechanisms of action and prospects for use of tea catechins such as EGCg as an anti-infective agent are discussed.
Anti-Infective Agents in Medicinal Chemistry (Formerly ?Current Medicinal Chemistry - Anti-Infective Agents) 12/2006; 6(1):57-62.
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ABSTRACT: IL-4 can suppress mast cell development from mouse spleen, bone marrow and peritoneal cells by an indirect process that is dependent on the presence of macrophages. Mast cells undergo apoptosis when exposed to supernatants collected from cultures of IL-4-stimulated peritoneal cells due to the IL-4-induced production of an apoptosis-inducing factor in the cultures. This effect of IL-4 is shown to be dependent on STAT6 signaling, because IL-4 and IL-13 do not suppress mast cell development from the spleen and peritoneal cells of STAT6-/- mice. Moreover, supernatants from cultures of IL-4- and IL-13-stimulated peritoneal cells of STAT6-/- mice do not exhibit apoptosis-inducing activity. We confirm, by using deficient mice, neutralizing antibodies and recombinant cytokines, that IL-4-induced apoptosis is not related to the well-known apoptosis-inducing factors Fas, Fas ligand, TNF-alpha, TRAIL, TGF-beta or perforin. These results demonstrate a novel mechanism whereby IL-4 and IL-13 can suppress mast cell development by inducing the production of an apoptosis-inducing factor from macrophages.
European Journal of Immunology 06/2006; 36(5):1275-84. · 5.10 Impact Factor
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ABSTRACT: Mast cell development from spleen cells was not triggered by prostaglandin E1 (PGE1) or dibutyryl cAMP (db-cAMP) during a 12 day culture when the spleen cells were obtained from C57BL/6N and DBA/1 mice, but mast cells did develop when the spleen cells were obtained from C3H/HeN, BALB/c and ICR mice. A lack of endogenous IFN-gamma in the initial 2 days of the culture period was responsible for the failure. This was confirmed by adding neutralizing anti-IFN-gamma antibody and rIFN-gamma to the cultures and by determining IFN-gamma levels in the spleen cell cultures. Th1 cells in the spleens of C57Bl and DBA/1 mice were much more sensitive to PGE1 and db-cAMP than Th1 cells from other inbred mice strains, and consequently, IFN-gamma production was inhibited in spleen cell cultures of C57BL and DBA/1 mice on addition of PGE1 or db-cAMP. Furthermore, the different sensitivities of Th1 cells to PGE and db-cAMP were dependent on the different levels of IL-12 p40 monomers or homodimers in the spleen cell cultures. As the endogenous specific inhibitors of IL-12 p70 (heterodimers of p40 and p35), large amounts of IL-12 p40 monomers or homodimers in the spleen cell cultures of C57BL and DBA/1 mice enhanced the ability of PGE1 and db-cAMP to inhibit IFN-gamma production by antagonizing the activity of IL-12 heterodimers. These results indicate that the strain-dependent development of mast cells from mouse splenocytes is related to endogenous IFN-gamma levels, which are regulated by PGE, db-cAMP, IL-12 p70 and IL-12 p40.
Immunology and Cell Biology 05/2006; 84(2):184-91. · 3.66 Impact Factor
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ABSTRACT: Cholesterol is necessary for the conversion of Vibrio cholerae hemolysin (VCH) monomers into oligomers in liposome membranes. Using different sterols, we determined the stereochemical structures of the VCH-binding active groups present in cholesterol. The VCH monomers are bound to cholesterol, diosgenin, campesterol, and ergosterol, which have a hydroxyl group at position C-3 (3betaOH) in the A ring and a C-C double bond between positions C-5 and C-6 (C-C Delta(5)) in the B ring. They are not bound to epicholesterol and dihydrocholesterol, which form a covalent link with a 3alphaOH group and a C-C single bond between positions C-5 and C-6, respectively. This result suggests that the 3betaOH group and the C-CDelta(5) bond in cholesterol are required for VCH monomer binding. We further examined VCH oligomer binding to cholesterol. However, this oligomer did not bind to cholesterol, suggesting that the disappearance of the cholesterol-binding potential of the VCH oligomer might be a result of the conformational change caused by the conversion of the monomer into the oligomer. VCH oligomer formation was observed in liposomes containing sterols with the 3betaOH group and the C-C Delta(5) bond, and it correlated with the binding affinity of the monomer to each sterol. Therefore, it seems likely that monomer binding to membrane sterol leads to the assembly of the monomer. However, since oligomer formation was induced by liposomes containing either epicholesterol or dihydrocholesterol, the 3betaOH group and the C-C Delta(5) bond were not essential for conversion into the oligomer.
Microbiology and Immunology 02/2006; 50(10):751-7. · 1.30 Impact Factor
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ABSTRACT: Catechin (epicatechin (EC), epicatechin gallate (ECg), epigallocatechin (EGC) and epigallocatechin gallate (EGCg)), which occur in green tea and black tea, possess strong bactericidal action. We observed a reactive oxygen species that was generated from the catechins as the active mechanism: and this reactive oxygen was identified. EGCg reacted with the dissolved oxygen in aqueous solution, resulting in the generation of hydrogen peroxide. Hydrogen peroxide production derived from EGCg rose with increasing pH. EGCg (0.22 mmol/l) in neutral solution (0.1 mol/l phosphate buffer pH 7.0: PBS) quantitatively generated 0.2 mmol/l hydrogen peroxide after 60 min incubation. The bactericidal effect of EGCg is dependent on hydrogen peroxide levels produced by EGCg; moreover, EGCg action was inhibited by treatment with catalase. Both bactericidal effects correlated closely when the effects of EGCg and hydrogen peroxide for the bacterium (9 of 10 kinds of bacterial strains) were examined. Therefore, hydrogen peroxide, which is generated by EGCg, appears to be involved in the bactericidal action of EGCg.
Biological & Pharmaceutical Bulletin 04/2004; 27(3):277-81. · 1.66 Impact Factor
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ABSTRACT: Human basophils may play a role in bronchial asthma. The effect of pranlukast on histamine release and LTC4 generation from human peripheral basophils was examined. Histamine release induced by FMLP and C5a was inhibited by pranlukast in concentration-dependent manner, whereas anti-IgE Ab-induced histamine release was not affected. Both anti-IgE Ab-and FMLP-induced LTC4 were inhibited by pranlukast. These results suggest that pranlukast may improve symptoms of bronchial asthma by inhibiting basophil function in addition to antagonizing Cys-LT receptor.
Arerugī = [Allergy] 02/2004; 53(1):19-23.
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ABSTRACT: We examined the antibacterial effects of epigallocatechin gallate (EGCg, the main constituent of tea catechins) against various strains of Staphylococcus and Gram-negative rods. Compared to the minimum inhibitory concentrations (MICs) of EGCg against S. aureus, S. epidermidis, S. hominis, and S. haemolyticus (50-100 micro g/ml), higher MICs (>or=800 micro g/ml) were observed against Gram-negative rods, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. And difference was observed between the binding abilities of EGCg with viable S. aureus and with E. coli. The bactericidal activity of EGCg for S. aureus was blocked dose-dependently by purified peptidoglycan but not by lipopolysaccharide or dextran. It was also found that peptone and protein, but not amino acids, in the culture medium greatly affected the antibacterial activity of EGCg. These results indicate that the structure of the bacterial cell wall and the different affinities of EGCg with the various cell wall components are responsible for the different susceptibilities of Staphylococcus and Gram-negative rods to EGCg.
Journal of Infection and Chemotherapy 02/2004; 10(1):55-8. · 1.80 Impact Factor
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ABSTRACT: Staphylococcal superantigens (SsAgs) have gained attention as one of the factors aggravating atopic dermatitis (AD) and several potential mechanisms of AD aggravation by SsAgs have been reported. Tea catechin has been found to have many unique antimicrobiological activities such as antibacterial, antiviral, antifungal and antitoxic effects. In the present study, we investigated the inhibitory effect of the green tea catechin extract, Polyphenon, and (-)-epigallocatechin gallate (EGCg) on staphylococcal enterotoxin B (SEB) and its mechanisms of action, and we also discuss the possibility of therapeutic benefits for AD patients of tea catechin. Polyphenon inhibited the lethal toxicity of SEB and the SEB-induced production of TNF-alpha, IFN-gamma and IL-4 following its intraperitoneal administration to BALB/c mice. Although Polyphenon is composed of several isomers among which EGCg is approximately 50% of the total, we considered that most of the inhibitory effect of Polyphenon in mice could be attributed to EGCg. EGCg was immediately bound to SEB molecules and neutralized SEB in a dose- and incubation time-dependent manner without molecular weight alteration of the SEB molecule. Furthermore, EGCg inhibited SEB-induced TNF-alpha and IFN- gamma production and IL-2, IFN-gamma, IL-10 and IL-12 p40 mRNA expression in human PBMCs from normal donors in a dose-dependent manner. Inhibition of SsAg-induced T-cell activation by catechin was observed in both in vivo and in vitro studies, suggesting that catechin may be useful in the treatment of AD.
Archives for Dermatological Research 10/2003; 295(5):183-9. · 2.28 Impact Factor
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ABSTRACT: Since green tea catechins are known to have antimicrobial activity against a variety of microorganisms, their possible effects on Helicobacter pylori in combination with antibiotics were examined. Fifty-six clinical isolates of H. pylori, including 19 isolates highly resistant to metronidazole (MTZ) and/or clarithromycin (CLR), were used to determine in vitro sensitivity to tea catechins. The MIC90 of both epigallocatechin gallate (EGCg) and epicatechin gallate (ECg) was 100 microg/ml. However, other tea catechins tested did not show any anti-H. pylori activity. Highly antibiotic-resistant clinical isolates showed a similar sensitivity to both EGCg and ECg. The kinetic study of antibacterial activity in liquid cultures revealed a relatively slow but strong activity on the growth of H. pylori. In combination with sub-MIC of amoxicillin (AMX), the antibacterial activity of AMX was significantly enhanced by the presence of EGCg. To estimate the general combination effect between EGCg and other antibiotics, such as MTZ and CLR, on the antibacterial activity against clinical isolates, the fraction inhibitory concentration (FIC) was determined by checkerboard study. The FIC indexes showed additive effects between EGCg and antibiotics tested. These results indicatethat EGCg may be a valuable therapeutic agent against H. pylori infection.
Current Microbiology 09/2003; 47(3):244-9. · 1.82 Impact Factor
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ABSTRACT: The combined effects of (–)-epigallocatechin gallate (EGCg) and β-lactams were investigated against various β-lactamase-producing clinical isolates, including 21 Staphylococcus aureus, 6 Escherichia coli, 3 Klebsiella pneumoniae and 8 Serratia marcescens strains. Penicillin in combination with EGCg at 12.5μg mL−1 showed the most potent synergy against 100% penicillinase-producing S. aureus. However, cefotaxime or imipenem in combination with higher concentration of EGCg (100 μg mL−1) only showed slight synergy against 2 of 17 Gram-negative rods. Similar to the effect on the penicillinase from S. aureus, however, EGCg also directly inhibited the extracted β-lactamases from the Gram-negative rods, thereby protecting β-lactams from inactivation. The different effects of the combinations on different β-lactamase-producing species were confirmed to be related to the cellular locations of β-lactamases. In contrast to a 32.7% extracellular fraction of total β-lactamase activity in a penicillinase-producing S. aureus, the fractions were 0.6%, 0.6% and 1.2% in a TEM-derived extended-spectrum β-lactamase-producing E. coli, an inhibitor-resistant β-lactamase-producing K. pneumoniae and an IMP-producing S. marcescens, respectively. In conclusion, the combination of penicillin with EGCg showed potent synergy against penicillinase-producing S. aureus in-vitro. The combinations of β-lactams and EGCg against β-lactamase-producing Gram-negative rods do indicate a limitation owing to the cellular location of β-lactamases.
Journal of Pharmacy and Pharmacology. 05/2003; 55(6):735 - 740.
