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Significant Inhibition (significant + inhibition)
Selected AbstractsPhytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004A. M. Quílez Agave intermixta Trel. (Maguey) and Cissus sicyoides L. (Bejuco caro) are Caribbean plant species from the Dominican Republic used locally in traditional popular medicine that have shown an anti-inflammatory effect in experimental animal models. A phytochemical analysis on these species allowed us the isolation and identification of the steroidal sapogenins hecogenin and diosgenin from Maguey and the hydroxystilbene resveratrol from Bejuco caro. The effects of these plant extracts and their isolated constituents on compound-48/80-induced histamine release from peritoneal mast cells were investigated. Significant inhibition was produced by 0.5 mg mL,1 of a methanolic extract of Bejuco (41.1%) and by its constituent resveratrol (82.4%) at a dose of 250 ,M. However, none of the steroidal sapogenins from A. intermixta showed a significant inhibitory effect on histamine release from mast cells. From these results, it can be deduced that the in-vitro anti-allergic activity towards the release of histamine from mast cells shown by the methanolic extract of C. sicyoides may be mediated by its constituent resveratrol and might contribute to the anti-inflammatory activity shown by this species. [source] Effect of Artemisinins and Amino Alcohol Partner Antimalarials on Mammalian Sarcoendoplasmic Reticulum Calcium Adenosine Triphosphatase ActivityBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Stephen Toovey Artemisinins exert their antiplasmodial action by inhibiting parasite PfATP6, a SERCA enzyme, and possess neurotoxic potential; mefloquine is neurotoxic and inhibits mammalian SERCA, an orthologue of PfATP6. SERCA in rabbit muscle was tested in vitro for inhibition by artemisinin and amino alcohol antimalarials. Significant inhibition of mammalian SERCA, as mean difference from uninhibited, control values was seen with both enantiomers of mefloquine: (+)-mefloquine (10 µM: ,35.83, 95% CI ,59.63 to ,12.03; 50 µM: ,54.06, 95% CI ,77.86 to ,30.26); (,)-mefloquine (10 µM: ,24.35, 95% CI ,41.56 to ,7.15; 50 µM: ,58.42, 95% CI ,75.62 to ,41.22); lumefantrine (1 µM: ,25.46, 95% CI ,45.82 to ,5.10; 5 µM ,34.83, 95% CI ,60.08 to ,9.58; 10 µM: ,25.80, 95% CI ,51.05 to ,0.55); desbutyl-lumefantrine (5 µM: ,50.16, 95% CI ,84.24 to ,16.08); dihydroartemisinin (1 µM: ,39.25, 95% CI ,63.74 to ,14.76; 5 µM: ,39.30, 95% CI ,64.88 to ,13.72). Dihydroartemisinin in higher concentrations (10 µM) stimulated SERCA activity: (+40.90, 95% CI 11.37 to 70.44). No statistically significant inhibition was seen with artemether at 1, 5 and 10 µM. Equimolar combinations of artemether and lumefantrine or of dihydroartemisinin and lumefantrine, when studied at concentrations that inhibit SERCA individually, failed to show any inhibition. Dihydroartemisinin, mefloquine, lumefantrine and desbutyl lumefantrine inhibit mammalian SERCA at periphysiological concentrations, although the neurotoxicity of mefloquine is not wholly attributable to this property. Candidate antimalarials should be screened pre-clinically for SERCA inhibition. [source] Comparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatusENVIRONMENTAL TOXICOLOGY, Issue 4 2008Winfred G. Aker Abstract Malathion inhibits the critical body enzyme, acetylcholinesterase (AChE). This capability requires that malathion should first be converted to malaoxon to become an active anticholinesterase agent. Conversion can be caused by oxidation in mammals, insects, plants, and in sunlight. In this study, the effects of malathion and malaoxon on catfish Ictalurus furcatus were evaluated. After 96-h exposures, the LC50 (concentration that causes 50% mortality) and IC50 (concentration that causes 50% enzyme inhibition) for malaoxon were lower than corresponding values for malathion. The overall mean 96-h LC50 is 17.0 ppm for malathion and 3.1 ppm for malaoxon. IC50 values for malathion are 8.5 ppm for brain, 10.3 ppm for liver, and 16.6 ppm for muscle. Corresponding values for malaoxon are 2.3, 3.7, and 6.8 ppm, respectively. All the AChE activities in malathion- and malaoxon-exposed catfish brain showed significant inhibition. The oxidation product malaoxon demonstrated higher inhibition on AChE activity than did malathion. Moreover, malaoxon showed significant inhibition on butyrylcholinesterase (BChE) in the liver if the concentrations were increased to more than 1 ppm. Malathion showed no difference between treatment group and control group. Compared with malathion, malaoxon showed higher inhibition on monoamine activity than that of malathion. The results indicated that the oxidative product malaoxon is more toxic than the parent compound malathion. AChE, BChE, and monoamine activities are confirmed as bioindicators of malathion exposure in blue catfish, I. furcatus. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Phosphate regulates uranium(VI) toxicity to Lemna gibba L. G3ENVIRONMENTAL TOXICOLOGY, Issue 1 2007Martin Mkandawire Abstract The influence of phosphate on the toxicity of uranium to Lemna gibba G3 was tested in semicontinuous culture with synthetic mine water developed as an analogue of surface water of two abandoned uranium mining and ore processing sites in Saxony, Germany. Six concentrations of uranium were investigated under five different supply regimes of PO43, at constant pH (7.0 ± 0.5) and alkalinity (7.0 ± 1.6 mg L,1 total CO32,). The results showed significant inhibition of specific growth rates in cultures exposed to the highest uranium concentrations (3500 and 7000 ,g U L,1) at lowest PO43, supply of 0.01 mg L,1. An increase of phosphate concentration from 0.01 to 8.0 mg L,1 resulted in an increase of EC50 from 0.9 ± 0.2 to 7.4 ± 1.9 mg L,1 (significant with Student's t test, P > 0.05). The accumulation of uranium in L. gibba increased exponentially with the increase in uranium concentration in cultures with 0.01 and 0.14 mg PO43, L,1. Accumulation also increased significantly when PO43, supply was increased from 0.14 to 1.36 mg PO43, L,1 for all uranium concentrations. However, as the supply of PO43, gradually increased from 1.36 to 8.0 mg PO43, L,1, uranium bioaccumulation increased slightly but insignificantly before leveling off. Uranium speciation modeling with PhreeqC geochemical code predicted increases in the proportions of uranyl phosphate species when PO43, concentrations increase in the media. Most of these uranyl phosphate species have a high probability of precipitation [saturation indices (SI) > 0.93]. Therefore, the alleviation of uranium toxicity to L. gibba with phosphates is due to interactions among components of the media, mainly uranyl and phosphate which results in precipitation. Consequently, bioavailable fractions of uranium to L. gibba are reduced. This might explain lack of consistent EC50 values for uranium to most aquatic organisms. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 9,16, 2007. [source] Persistent inhibition of human natural killer cell function by ziram and pentachlorophenolENVIRONMENTAL TOXICOLOGY, Issue 4 2005Thyneice R. Taylor Abstract Ziram is a currently used agricultural fungicide. It is also used as an additive in the production of latex gloves. Because of these uses, there is a potential for human exposure to this compound. Pentachlorophenol (PCP) has been used as an insecticide, fungicide, disinfectant, and ingredient in antifouling paints. Currently, it is used as a wood preservative for power-line poles and fence posts. Measurable levels of PCP have been detected in human blood and urine. In previous studies we demonstrated that both these compounds could cause very significant inhibition of the tumor-killing function of human natural killer (NK) cells. NK lymphocytes play a central role in immune defense against viral infection and the formation of primary tumors. So interference with their function could increase the risk of tumor development. In the present study we examined the effects of exposure to ziram or PCP of brief duration (1 h) on the ability of NK cells to destroy tumor cells. NK cells were exposed to either ziram (5,0.5 ,M) or PCP (10,5 ,M) for 1 h followed by 0 h, 24 h, 48 h, or 6 days in compound-free media and then were tested for the ability to lyse as well as to bind tumor cells. A 1-h exposure to as little as 2.5 ,M ziram decreased the ability of NK cells to lyse target tumor cells, which persisted up to 6 days following exposure. The loss of lytic function for from 24 h to 6 days following exposure was accompanied by a comparable loss of NK capacity to bind tumor cells. Exposure to 10 ,M PCP for 1 h caused a progressive loss (greater than 80%) of lytic function within 6 days of exposure. In contrast to ziram, PCP exposure caused no accompanying loss of binding function. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 418,424, 2005. [source] Sublethal responses of wolf spiders (Lycosidae) to organophosphorous insecticidesENVIRONMENTAL TOXICOLOGY, Issue 5 2002S. Van Erp Abstract The activities of cholinesterase (ChE) and glutathione S -transferase (GST) enzymes were assessed in the wolf spider (Lycosa hilaris) as biomarkers of organophosphate contamination in agricultural ecosystems. Spiders were exposed to simulated field rates of two commercially available organophosphorous insecticides [Basudin (diazinon) and Lorsban (chlorpyrifos)] under laboratory conditions. In terms of survival, chlorpyrifos and diazinon were more toxic to male than to female wolf spiders, but gender-specific differences in ChE activities were not evident. Cholinesterase activity in male spiders was inhibited to 14% and 61% of control activity by Basudin and Lorsban, respectively. Gluthathione S -transferase activity was not affected by either pesticide. Mortality and biomarker responses in the wolf spider were further investigated following the application of Basudin to pasture. Wolf spiders were deployed into field mesocosms; after 24 h mortality was 40%, and surviving spiders displayed significant inhibition of ChE activity (87%) compared with controls. Cholinesterase activity in spiders exposed for subsequent 24- or 48-h time periods was monitored until it returned to control levels 8 days post-application. Inhibition of ChE activity after a single application of Basudin indicate the potential use of this enzyme in wolf spiders as a biomarker for evaluating organophosphate contamination. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 449,456, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10078 [source] Hepatic microsomal cytochrome P450 enzyme activity in relation to in vitro metabolism/inhibition of polychlorinated biphenyls and testosterone in Baltic grey seal (Halichoerus grypus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2003Hongxia Li Abstract Among other factors, cytochrome P450 (CYP) enzyme activity determines polychlorinated biphenyl (PCB) bioaccu-mulation, biotransformation, and toxicity in exposed species. We measured the oxidative metabolism in vitro of 12 PCB congeners, representing structural groups based on the number and position of the chlorine atoms, by the hepatic microsomes of one Baltic grey seal (Halichoerus grypus). Microsomal metabolism was observed for several PCBs with vicinal H atoms exclusively in the ortho and meta positions and without any ortho -Cl substituents (CB-15 [4,4,-Cl2] and CB-77 [3,3,,4,4,-Cl4]), vicinal meta and para -H atoms (CB-52 [2,2,,5,5,-Cl4], and ,101 [2,2,,4,5,5,-Cl5]) or with both characteristics in combination with either only one ortho -Cl (CB-26 [2,3,,5-Cl3], CB-31 [2,4,,5-Cl3]) or two ortho -Cl substituents (CB-44 [2,2,,3,5,-Cl4]). To allocate PCB biotransformation to specific CYPs, the inhibitive effect of compounds with known CYP-specific inhibition properties was assessed on in vitro PCB metabolism and on regio- and stereospecific testosterone hydroxylase activities. Metabolic inhibition was considered relevant at concentrations ,1.0 ,M because these inhibitors became decreasingly selective at higher concentrations. At <1.0 ,M, ellipticine (CYP1A1/2 inhibitor) selectively inhibited CB-15, ,26, ,31, and ,77 metabolism, with no significant inhibition of CB-44, ,52, and ,101 metabolism. Inhibition of CB-52 and ,101 metabolism by chloramphenicol (CYP2B inhibitor) started at 1.0 ,M and maximized at about 100% at 10 ,M. Ketoconazole (CYP3A inhibitor) appeared to selectively inhibit CB-26, ,31, and ,44 metabolism relative to CB-15, ,77, and ,52 at concentrations ,1.0 ,M. Major testosterone metabolites formed in vitro were 2,-(CYP3A), 6,- (CYP3A, CYP1A), and 16,- (CYP2B) hydroxytestosterone and androstenedione (CYP2B, CYP2C11). The CYP forms indicated are associated with the specific metabolism of testosterone in laboratory animals. Inhibition of 2,- and 6,-hydroxytestosterone formation at ellipticine and ketoconazole concentrations ,1.0,M suggested that both inhibitors were good substrates of CYP3A-like enzymes in grey seal. Chloramphenicol (model for CYP2B) is apparently not a good inhibitor of CYP1A and CYP3A activities in grey seal because the chemical did not inhibit any metabolic route of testosterone at concentrations from 0.1 to 10 ,M. Our findings demonstrated that at least CYP1A- and CYP3A-like enzymes in the liver of grey seals are capable of metabolizing PCBs with ortho - meta and/or meta - para vicinal hydrogens. A CYP2B form might also be involved, but this could not be proven by the results of our experiments. Defining the profiles of CYP enzymes that are responsible for PCB biotransformation is necessary to fully understand the bioaccumulation, toxicokinetics, and risk of PCB exposure in seals and other free-ranging marine mammals. [source] Ecotoxicological effects of hexahydro-1,3,5-trinitro-1,3,5-triazine on soil microbial activities,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2001Ping Gong Abstract Although hexahydro-1,3,5-trinitro-1,3,5-triazine (also called RDX or hexogen) is a potentially toxic explosive compound that persists in soil, its ecotoxicological effects on soil organisms have rarely been assessed. In this study, two uncontaminated garden soils were spiked with 10 to 12,500 mg RDX/kg dry soil. Soil microbial activities, i.e., potential nitrification, nitrogen fixation, dehydrogenase, basal respiration, and substrate-induced respiration were chosen as bioindicators and were determined after 1-, 4-, and 12-weeks of exposure. Experimental results indicate that RDX showed significant inhibition (up to 36% of control) on indigenous soil microbial communities over the period of this study. All five bioindicators responded similarly to the RDX challenge. The length of exposure also affected the microbial toxicity of RDX, with 12-week exposure exerting more significant effects than the shorter exposure periods, suggesting that soil microorganisms might become more vulnerable to RDX when exposure is extended. The estimated lowest observable adverse effect concentration of RDX was 1,235 mg/kg. No biodegradation products of RDX were detected at all three sampling times. Compared with 2,4,6-trinitrotoluene (TNT), RDX is less toxic to microbes, probably because of its resistance to biodegradation under aerobic conditions, which precludes metabolic activation of nitro groups. [source] rTMS Reveals Premotor Cortex Dysfunction in Frontal Lobe EpilepsyEPILEPSIA, Issue 2 2007Wolfgang N. Löscher Summary:,Purpose: Studies of motor cortex excitability provided evidence that focal epilepsies may alter the excitability of cortical areas distant from the epileptogenic zone. In order to explore this hypothesis we studied the functional connectivity between premotor and motor cortex in seven patients with frontal lobe epilepsy and seizure onset zone outside the premotor or motor cortex. Methods: Low-frequency subthreshold repetitive transcranial magnetic stimulation was applied to the premotor cortex and its impact on motor cortex excitability was measured by the amplitude of motor-evoked potentials in response to direct suprathreshold stimulation of the motor cortex. Results: Stimulation of the premotor cortex of the non-epileptogenic hemisphere resulted in a progressive and significant inhibition of the motor cortex as evidenced by a reduction of motor evoked potential amplitude. On the other hand, stimulation of the premotor cortex of the epileptogenic hemisphere failed to inhibit the motor cortex. The reduced inhibition of the motor cortex by remote areas was additionally supported by the significantly shorter cortical silent periods obtained after stimulation of the motor cortex of the epileptogenic hemisphere. Conclusion: These results show that the functional connectivity between premotor and motor cortex or motor cortex interneuronal excitability is impaired in the epileptogenic hemisphere in frontal lobe epilepsy while it is normal in the nonepileptogenic hemisphere. [source] Vorinostat enhances the antimyeloma effects of melphalan and bortezomibEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Richard A. Campbell Abstract Objectives:, Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. Methods:, RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferation was measured using the MTS [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfphophenyl)-2H-tetrazolium, inner salt] assay. Severe combined immunodeficient mice bearing LAG,-1B tumors were treated with vorinostat [30, 60, or 100 mg/kg daily for five consecutive days per week (qd×5d), 100 or 300 mg/kg daily for 2 d/wk (qd×2d)], melphalan (1, 3, or 10 mg/kg qd×1d), bortezomib (0.25 or 0.5 mg/kg qd×2d), or combinations thereof for 35 d. Tumor growth was determined via measurement of human immunoglobulin G (hIgG) levels and tumor volume. Results and Conclusions:, Vorinostat enhanced the anti-MM effects of melphalan and bortezomib in vitro. Synergism was observed with vorinostat and melphalan in RPMI8226 and U266 cell lines. Vorinostat 100 mg/kg in combination with melphalan 3 mg/kg resulted in significant inhibition of tumor growth in vivo, compared with control (tumor volume P = 0.0001; hIgG P = 0.0001), single-agent vorinostat (tumor volume P = 0.0025; hIgG P = 0.0137), and single-agent melphalan (tumor volume P = 0.0043; hIgG P = 0.0426). Vorinostat also enhanced the antimyeloma effects of bortezomib in vivo. Vorinostat enhances the anti-MM activity of melphalan and bortezomib in vitro and in vivo. This study provides rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment of MM. [source] Study of cord blood natural killer cell suppressor activityEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2001S. El Marsafy Abstract: We tested the immunosuppressive effect of cord blood (CB) natural killer (NK) cells using highly purified CB NK cells in mixed lymphocyte cultures (MLC) containing autologous CB T cells as responders. Control cultures were done without NK cells. Our findings revealed that CB NK cells induced a dose-dependent inhibition of T lymphocyte proliferation as evidenced by decreased 3H-thymidine incorporation in MLC. The T cell alloproliferation was significantly decreased in the presence of an NK cell to responder cell ratio of 0.1, 0.2 or 0.4 compared with control cultures done without NK cells (p=0.02, 0.003 and 0.0002, respectively). T lymphocyte inhibition was also achieved using irradiated CB NK cells and still demonstrable on addition of disparate CB NK and T cells to the MLC. In agreement with previous reports, adult blood NK cells inhibited the alloreactive T cells in the MLC using adult T lymphocytes as responders. Compared to control cultures done without NK cells, statistically significant inhibition of 3H-thymidine incorporation in MLC was observed at a ratio of NK cells to responder cells ratio of 0.2 or 0.4 (p=0.02). To investigate the mechanism whereby CB NK cells can interfere with the development of alloreactive T cells in MLC, we measured the tumour necrosis factor-, (TNF-,) concentrations in MLC supernatants using NK cell-depleted or unseparated CB mononuclear cells (MNC) as responders. The results revealed significantly high levels of TNF-, in the absence of NK cells (p=0.007). We conclude that CB NK cells suppress alloreactive T lymphocytes as do their counterparts in adult blood. However, the high NK to T cell ratio in CB could contribute to a more marked suppressive potential compared to that in adult blood. The mechanism of NK-mediated inhibition is likely related to disruption of the TNF-, pathway of T-lymphocyte activation. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] Spirocyclic Pyridoazepine Analogues of Galanthamine: Synthesis, Modelling Studies and Evaluation as Inhibitors of AcetylcholinesteraseEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2008Sofie Vanlaer Abstract Spirocyclic pyridoazepines, designed as simplified analogues of the alkaloid galanthamine, were synthesised and evaluated as inhibitors of acetylcholinesterase. The key cyclisation step involved internal displacement of 2-chloro or 2-iodopyridine by either nucleophilic aromatic substitution or a Heck reaction. The target compounds showed significant inhibition of acetylcholinesterase but lower than that of galanthamine. This result could be rationalised by comparative docking simulation studies based on the known crystal structure of the acetylcholinesterase,galanthamine complex; multiple hydrogen bonding of a cocrystallised water molecule to both the receptor and the ligand was found to be of crucial importance for effective binding to the active site of the enzyme. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Inhibition of the D -alanine:D -alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wallFEBS JOURNAL, Issue 12 2005Juergen J. May The surface charge as well as the electrochemical properties and ligand binding abilities of the Gram-positive cell wall is controlled by the d -alanylation of the lipoteichoic acid. The incorporation of d -Ala into lipoteichoic acid requires the d -alanine:d -alanyl carrier protein ligase (DltA) and the carrier protein (DltC). We have heterologously expressed, purified, and assayed the substrate selectivity of the recombinant proteins DltA with its substrate DltC. We found that apo-DltC is recognized by both endogenous 4,-phosphopantetheinyl transferases AcpS and Sfp. After the biochemical characterization of DltA and DltC, we designed an inhibitor (d -alanylacyl-sulfamoyl-adenosine), which is able to block the d -Ala adenylation by DltA at a Ki value of 232 nmin vitro. We also performed in vivo studies and determined a significant inhibition of growth for different Bacillus subtilis strains when the inhibitor is used in combination with vancomycin. [source] Kinetic and crystallographic analysis of complexes formed between elastase and peptides from ,-caseinFEBS JOURNAL, Issue 10 2001Penny A. Wright Human ,-casomorphin-7 (NH2 -Tyr-Pro-Phe-Val-Glu-Pro-Ile-CO2H) is a naturally occurring peptide inhibitor of elastase that has been shown to form an acyl-enzyme complex stable enough for X-ray crystallographic analysis at pH 5. To investigate the importance of the N-terminal residues of the ,-casomorphin-7 peptide for the inhibition of elastase, kinetic and crystallographic analyses were undertaken to identify the minimum number of residues required for effective formation of a stable complex between truncated ,-casomorphin-7 peptides and porcine pancreatic elastase (PPE). The results clearly demonstrate that significant inhibition of PPE can be effected by simple tri-, tetra-and pentapeptides terminating in a carboxylic acid. These results also suggest that in vivo regulation of protease activity could be mediated via short peptides as well as by proteins. Crystallographic analysis of the complex formed between N -acetyl-Val-Glu-Pro-Ile-CO2H and PPE at pH 5 (to 1.67 Å resolution) revealed an active site water molecule in an analogous position to that observed in the PPE/,-casomorphin-7 structure supportive of its assignment as the ,hydrolytic water' in the deacylation step of serine protease catalysis. [source] Pgt1, a glutathione transporter from the fission yeast Schizosaccharomyces pombeFEMS YEAST RESEARCH, Issue 6 2008Anil Thakur Abstract The Schizosaccharomyces pombe ORF, SPAC29B12.10c, a predicted member of the oligopeptide transporter (OPT) family, was identified as a gene encoding the S. pombe glutathione transporter (Pgt1) by a genetic strategy that exploited the requirement of the cys1a, strain of S. pombe (which is defective in cysteine biosynthesis) for either cysteine or glutathione, for growth. Disruption of the ORF in the cys1a, strain led to an inability to grow on glutathione as a source of cysteine. Cloning and subsequent biochemical characterization of the ORF revealed that a high-affinity transporter for glutathione (Km=63 ,M) that was found to be localized to the plasma membrane. The transporter was specific for glutathione, as significant inhibition in glutathione uptake could be observed only by either reduced or oxidized glutathione, or glutathione conjugates, but not by dipeptides or tripeptides. Furthermore, although glu,cys,gly, an analogue of glutathione (,-glu,cys,gly), could be utilized as a sulphur source, the growth was not Pgt1 dependent. This further underlined the specificity of this transporter for glutathione. The strong repression of pgt1+ expression by cysteine suggested a role in scavenging glutathione from the extracellular environment for the maintenance of sulphur homeostasis in this yeast. [source] Mechanism of catabolite repression in the bgl operon of Escherichia coli: involvement of the anti-terminator BglG, CRP-cAMP and EIIAGlc in mediating glucose effect downstream of transcription initiationGENES TO CELLS, Issue 4 2000Abhilasha Gulati Background Expression of the bgl operon of Escherichia coli, involved in the regulated uptake and utilization of aromatic ,-glucosides, is extremely sensitive to the presence of glucose in the growth medium. We have analysed the mechanism by which glucose exerts its inhibitory effect on bgl expression. Results Our studies show that initiation of transcription from the bgl promoter is only marginally sensitive to glucose. Instead, glucose exerts a more significant inhibition on the elongation of transcription beyond the rho-independent terminator present within the leader sequence. Transcriptional analyses using plasmids that carry mutations in bglG or within the terminator, suggest that the target for glucose-mediated repression is the anti-terminator protein, BglG. Introduction of multiple copies of bglG or the presence of mutations that inhibit its phosphorylation by Enzyme IIBgl (BglF), result in loss of glucose repression. Studies using crp, cya and crr strains show that both CRP-cAMP and the Enzyme IIAGlc (EIIAGlc) are involved in the regulation. Although transcription initiation is normal in a crp, cya double mutant, no detectable transcription is seen downstream of the terminator, which is restored by a mutation within the terminator. Transcription past the terminator is also partly restored by the addition of exogenous cAMP to glucose-grown cultures of a crp+ strain. Glucose repression is lost in the crr mutant strain. Conclusions The results summarized above indicate that glucose repression in the bgl operon is mediated at the level of transcription anti-termination, and glucose affects the activity of BglG by altering its phosphorylation by BglF. The CRP-cAMP complex is also involved in this regulation. The results using the crr mutant suggest a negative role for EIIAGlc in the catabolite repression of the bgl genes. [source] Fault interactions and subduction tectonics: a re-examination of the Weber, New Zealand, earthquake sequence of 1990GEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2003Russell Robinson SUMMARY Two moderate magnitude (Mw= 6.2 and 6.4) earthquakes in the Hikurangi subduction margin, North Island, New Zealand, occurred 3 months apart in 1990. The epicentres are nearly coincident, but the first (Weber 1, primarily normal faulting) occurred within the subducting Pacific Plate (depth about 28 km) and the second (Weber 2, a mix of thrusting and right-lateral motion) occurred within the overlying Australian Plate (depth about 13 km), the plate interface in between. The plate interface is interpreted to be locked trenchward (SE) from about the position of these events, with a transition to aseismic slip further down-dip to the NW. Several stress interaction questions are examined. First, to see whether Weber 1 triggered Weber 2, a range of possible mainshock parameters are used to calculate induced changes in the static Coulomb failure stress (,CFS). In most cases the results are consistent with triggering. Secondly, previous work showed that the rate of aftershock occurrence for Weber 1 decreased markedly about 35 days before Weber 2, recovering afterwards. To see whether aseismic pre-slip on the Weber 2 fault, as predicted by rate and state friction, could be the cause of the decrease, the same fault parameters have been used in reverse. The results are ambiguous, some fault parameters giving results consistent with the hypothesis and others not. The amount of pre-slip required for significant inhibition, however, is about equal to that in the mainshock and distributed over the entire fault plane. Thirdly, observations of episodic, aseismic slip down-dip from locked sections of other plate interfaces are becoming more common. Could such slip have triggered both Weber events? The induced changes in CFS for such slip are uniformly positive on the Weber 1 fault plane, and mostly positive on the Weber 2 fault plane, so the answer is yes. Although there is no independent evidence for aseismic slip prior to the Weber sequence, this case shows that such slip may trigger events on other nearby faults, besides loading the locked section of the plate interface. Static stress triggering considerations are thus likely to be important in subduction environments. [source] Inhibition of 13-cis retinoic acid-induced gene expression of homeobox B7 by thalidomideINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007an Milanovi Abstract Thalidomide and 13-cis retinoic acid (RA) show anticancer effects as sole agents or in combination with other drugs. However, induction of homeobox (HOX) gene expression by 13-cis RA may contribute to tumor progression thereby potentially limiting its efficacy. The purpose was to test if thalidomide can inhibit 13-cis RA-induced HOXB7 expression and whether thalidomide may enhance the antiproliferative effect of 13-cis RA in U343MG glioblastoma cells. Quantitative real-time PCR showed significant inhibition of 13-cis RA-induced HOXB7 expression by thalidomide with IC50 , 0.1,0.2 ,g/ml when given simultaneously with 13-cis RA but not when administered 18h later (p < 0.0001). 13-cis RA alone inhibited proliferation and colony formation in a concentration-dependent manner whereas growth inhibition by thalidomide alone at 5,100 ,g/ml was constant at 80,90% of controls. At 10% serum concentration, growth inhibition by a combination of the 2 drugs was additive but at 1% serum, growth inhibition was synergistic. It is concluded that thalidomide inhibits the RA-induced HOXB7 expression in glioblastoma cells and that 13-cis RA/thalidomide combinations can in principle enhance cytotoxicity. The improved cell kill induced by thalidomide is attributed to downregulation of growth stimulatory factors induced by 13-cis RA. Implications for the modus operandi of thalidomide in embryogenesis are noted. © 2007 Wiley-Liss, Inc. [source] Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental modelINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Sven A. Lang Abstract The mammalian target of rapamycin (mTOR) has become an interesting target for cancer therapy through its influence on oncogenic signals, which involve phosphatidylinositol-3-kinase and hypoxia-inducible factor-1, (HIF-1,). Since mTOR is an upstream regulator of HIF-1,, a key mediator of gastric cancer growth and angiogenesis, we investigated mTOR activation in human gastric adenocarcinoma specimens and determined whether rapamycin could inhibit gastric cancer growth in mice. Expression of phospho-mTOR was assessed by immunohistochemical analyses of human tissues. For in vitro studies, human gastric cancer cell lines were used to determine S6K1, 4E-BP-1 and HIF-1, activation and cancer cell motility upon rapamycin treatment. Effects of rapamycin on tumor growth and angiogenesis in vivo were assessed in both a subcutaneous tumor model and in an experimental model with orthotopically grown tumors. Mice received either rapamycin (0.5 mg/kg/day or 1.5 mg/kg/day) or diluent per intra-peritoneal injections. In addition, antiangiogenic effects were monitored in vivo using a dorsal-skin-fold chamber model. Immunohistochemical analyses showed strong expression of phospho-mTOR in 60% of intestinal- and 64% of diffuse-type human gastric adenocarcinomas. In vitro, rapamycin-treatment effectively blocked S6K1, 4E-BP-1 and HIF-1, activation, and significantly impaired tumor cell migration. In vivo, rapamycin-treatment led to significant inhibition of subcutaneous tumor growth, decreased CD31-positive vessel area and reduced tumor cell proliferation. Similar significant results were obtained in an orthotopic model of gastric cancer. In the dorsal-skin-fold chamber model, rapamycin-treatment significantly inhibited tumor vascularization in vivo. In conclusion, mTOR is frequently activated in human gastric cancer and represents a promising new molecular target for therapy. © 2007 Wiley-Liss, Inc. [source] Interactions between N,acetylcysteine and sodium selenite in modulating the clastogenicity of urethane and 2,acetylaminofluorene in miceINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Roumen M. Balansky Abstract Combined treatment with different agents represents a promising approach in cancer chemoprevention. Therefore, it is useful to assess in preclinical models the efficacy of combinations that are selected by taking into account mechanistic considerations. We designed 2 studies evaluating the interaction between N,acetylcysteine (NAC) and sodium selenite (Se), both given with the drinking water to Balb/c mice, in modulating clastogenic effects in bone marrow polychromatic erythrocytes. In a first study, a single i.p. injection of urethane considerably enhanced the frequency of micronucleated cells. While NAC produced a significant inhibition, Se further enhanced urethane clastogenicity. When given in combination at the same doses, NAC prevented the adverse effect of Se. In a second study, a single i.p. injection of 2,acetylaminofluorene enhanced the frequency of micronucleated cells. Se did not reduce this effect to a significant extent, while NAC produced a dose,dependent inhibition. When tested at the lower dose in combination with Se, the protective effect of NAC was unchanged. Especially in association with Se, NAC also prevented the toxicity of 2,acetylaminofluorene by normalizing the ratio of polychromatic to normochromatic erythrocytes. In conclusion, NAC attenuated the clastogenicity of both urethane and 2,acetylaminofluorene and the toxicity of this aromatic amine. In addition, NAC prevented the clastogenic and toxic effects resulting from the interaction of Se with urethane. Together with the findings of previous studies, it appears that, besides its intrinsic protective properties in carcinogenesis, NAC is capable of attenuating the adverse effects of several cytotoxic drugs and chemopreventive agents. © 2003 Wiley-Liss, Inc. [source] Cytotoxic T lymphocyte mediated recognition of human pancreatic cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2002Matthias Peiper Abstract T lymphocytes play an important role in tumor rejection and their response to human malignant melanoma has been well documented. In contrast, the existence of cytotoxic T lymphocytes (CTL) to pancreatic cancer remains unclear. Tumor-associated lymphocytes (TAL) and peripheral blood monocytes (PBMC) were isolated from pancreatic cancer patients. Tumor-specific CTL were generated from TAL and PBMC using solid-phase anti-CD3, low-dose IL-2 (50 IU/ml) and repetitive autologous tumor stimulation. The specificity of CTL was tested in standard cytotoxicity assays using autologous tumor cells, autologous fibroblasts when available, several allogeneic pancreatic tumor cells and the NK-sensitive cell line K562. Anti-HLA-Class I MAb, W6/32, was used to demonstrate that tumor-specific CTL were HLA-Class I restricted. HLA-molecules of human pancreatic cancer cells were washed out using acid elution. Eight consecutive, histologically confirmed pancreatic cancer specimen as well as peripheral blood mononuclear cells were analyzed. CTL were capable of lysing autologous tumor cells significantly after 3 stimulations with autologous tumor cells. T cell mediated recognition was HLA-Class I restricted as shown by incubation with MAb anti-HLA-Class I. In case of HLA-A2 positivity, incubation of tumor cells in cytotoxicity assays resulted in significant inhibition. Autologous fibroblasts or K562 cells were lysed significantly less. HLA-Class I molecule elution resulted in significantly lower recognition of these cells by CTL. These results show for the first time in a larger series the possibility of generating CTL in human pancreatic cancer. The identification of new tumor associated antigens or tumor antigens will be crucial for establishing new treatment strategies. © 2002 Wiley-Liss, Inc. [source] TCDD causes suppression of growth and differentiation of MCF10A, human mammary epithelial cells by interfering with their insulin receptor signaling through c-Src kinase and ERK activationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2005Sujin Park Abstract One of the proposed mechanisms of carcinogenic action of TCDD (=dioxin) on breast cells is that it causes significant inhibition of proper differentiation of mammary duct epithelial cells and thereby increases the number of terminal end buds, which are susceptible to other carcinogens (Fenton et al., Toxicol Sci 2002;67:63,74; Brown et al., Carcinogenesis 1998; 19:1623,1629; Lamartiniere, J Mammary Gland Biol Neoplasia 2002;7:67,76). To address this topic, we selected MCF10A, a line of immortalized normal human breast epithelial cells as an in vitro model. An initial effort was made to optimize the cultural condition of MCF10A cells to promote the cell differentiation effect of insulin. Under this condition, TCDD clearly antagonized the action of insulin only in the presence of cholera toxin that is known to promote the differentiation of normal human breast epithelial cells. To test the hypothesis that TCDD-induced c-Src kinase activation is casually related to this compound's antagonistic action against insulin, we treated MCF10A cells with two c-Src blocking agents, an anti-Src antisense oligonucleotides blocker and a known specific inhibitor of c-Src kinase, PP-2 and studied the effect of insulin and TCDD on cell proliferation. The results showed that, in cells treated with either of these two c-Src blocking agents, the antagonistic effect of TCDD disappeared. It was also found that agents which specifically block the activation of ERK could also abrogate the action of TCDD to suppress insulin signaling. Together, these results indicate that the mechanism of the antagonistic action of TCDD on insulin signaling is mainly mediated through c-Src signaling through activation of ERK. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:322,331, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20040 [source] Osteoclastogenesis-Related Antigen, a Novel Molecule on Mouse Stromal Cells, Regulates Osteoclastogenesis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2003Satoshi Arai Abstract Osteoclastogenesis is regulated by RANKL expressed on stromal cells. In this study, we sought to isolate a new surface molecule regulating osteoclastogenesis on stromal cells by generating monoclonal antibodies. A rat was immunized with the mouse stromal cell line, TSB13, which can support osteoclastogenesis, and a monoclonal antibody, A15-1, was obtained. A15-1 bound to a surface antigen on TSB13 cells, termed osteoclastogenesis-related antigen (OCRA), and immunoprecipitation with this antibody revealed that OCRA was a 220-kDa molecule. By means of flow cytometry, the A15-1 antigen (OCRA) was found to be expressed on various mesenchymal cell lines but not on hematopoietic cell lines, and the expression level of OCRA on the TSB13 cells was slightly increased by treatment with 1,,25(OH)2D3. When osteoclast progenitors and TSB13 cells were co-cultured in the presence of 1,,25(OH)2D3, the addition of A15-1 inhibited osteoclast differentiation in a dose-dependent manner; however, no significant inhibition of soluble RANKL-induced osteoclastogenesis was observed, suggesting that A15-1 inhibited only stromal cell-dependent osteoclastogenesis. The same inhibitory effect of A15-1 was also observed when primary bone marrow-derived stromal cells were used. The osteoclastogenesis-promoting effects of other osteotropic factors, such as parathyroid hormone (PTH) and interleukin (IL)-1,, were also inhibited by A15-1. Time-course analysis of osteoclast differentiation in vitro indicated that the initial 2 days of treatment with A15-1 was sufficient for inhibition, suggesting that A15-1 inhibits the early stages of osteoclast differentiation. Finally, we investigated the in vivo effects of A15-1 on PTH-induced hypercalcemia in mice. Treatment with A15-1 significantly decreased the osteoclast surface in the PTH-administered mice. Taken together, our data indicate that OCRA, a novel A15-1-detected antigen, regulates stromal cell-dependent osteoclastogenesis. [source] Methylene blue inhibits angiogenesis in chick chorioallontic membrane through a nitric oxide-independent mechanismJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006N. Zacharakis Abstract Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study was to evaluate the effect of methylene blue in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, methylene blue inhibited angiogenesis in a concentration-dependent manner. In addition, when methylene blue was combined with sodium nitroprusside, a spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident which was comparable with that observed by the application of methylene blue alone. Sodium nitroprusside, alone, caused a significant inhibition in basal angiogenesis. These results provide evidence that methylene blue inhibits angiogenesis independently of nitric oxide pathway and suggest that methylene blue may be useful for treating angiogenesis-dependent human diseases. [source] The green tea compound, (,)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Kimberly M. Rieger-Christ Abstract Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (,)-epigallocatechin gallate (EGCG,the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC50 range of 70,87 µM. At a concentration of 20 µM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P,,,0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. J. Cell. Biochem. 102: 377,388, 2007. © 2007 Wiley-Liss, Inc. [source] Functional analysis of CBP/p300 in embryonic orofacial mesenchymal cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2006D.R. Warner Abstract CREB binding protein (CBP) and the close structural homolog, p300, are nuclear coactivators of multiple signaling pathways that play important roles in embryonic development and cellular homeostasis. TGF, regulates the proliferation rate of many cell types and has been demonstrated to inhibit the growth rate of mouse embryonic maxillary mesenchymal (MEMM) cells. The role of CBP and p300 in TGF,-mediated control of proliferation of MEMM cells was thus investigated using an in vitro gene knockdown approach. TGF, reporter assays demonstrated that p300 mRNA knockdown via targeted siRNAs led to a reduction in the response to TGF,, whereas knockdown of CBP by the same approach had an insignificant effect. In MEMM cell proliferation assays, siRNA-mediated knockdown of CBP and/or p300 had little impact upon TGF,-mediated growth inhibition; however, the basal rate of proliferation was increased. Inhibition of p300 activity via overexpression of a dominant-negative mutant (p300,C/H3) led to significant inhibition of TGF,-mediated activation of p3TP-lux. As with the siRNA knockdown approach, p300,C/H3 also increased the basal rate of cell proliferation of MEMM cells. CBP/p300 siRNA knockdown had a significant but incomplete inhibition of TGF,-induction of matrix metalloproteinase-9 (gelatinase B) expression. These data demonstrate that p300 is involved in Smad-mediated transcription of p3TP-lux, however, its role (and that of CBP) in biological processes such as the control of cell proliferation and extracellular matrix metabolism is more complex and may be mediated via mechanisms beyond coactivator recruitment. J. Cell. Biochem. 99: 1374,1379, 2006. © 2006 Wiley-Liss, Inc. [source] Antiplaque and antigingivitis effectiveness of a hexetidine mouthwashJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2003N. C. Sharma Abstract Objective: To assess the antiplaque/antigingivitis efficacy of a hexetidine-containing mouthwash. Methods: This examiner-blind, parallel group, controlled clinical study examined the effectiveness of a hexetidine (0.1%) mouthwash both in inhibiting the development of supragingival plaque and in reducing gingivitis. One hundred and thirty-four adult subjects completed the 2-week experimental gingivitis model study. Following baseline examinations, which included plaque index, modified gingival index and gingival bleeding index, subjects received a full dental prophylaxis. Subjects were randomly assigned to one of three mouthwashes (hexetidine 0.1%, chlorhexidine 0.12% (positive control) or a 5% hydroalcohol negative control) and commenced three times daily supervised rinsing as their sole method of oral hygiene. All indices were rescored after 2 weeks. Results: Compared to the negative control group, the hexetidine group demonstrated a statistically significant inhibition and reduction of supragingival plaque and gingival inflammation with reductions of 6.3%, 33.5% and 56% for gingivitis, plaque and gingival bleeding, respectively. The results of the chlorhexidine group were used to validate the study. Conclusion: The study confirms the efficacy of a hexetidine rinse in reducing supragingival plaque and gingival inflammation. Zusammenfassung Zielsetzung: Untersuchung der Antiplaque- und Antigingivitiseffektivität einer Hexetidin-Mundspüllösung. Methoden: Diese kontrollierte klinische Studie mit verblindetem Untersucher im Parallelarm-Design untersuchte die Effektivität einer Hexitidin-Mundspüllösung (0,1%) sowohl für die Hemmung supragingivaler Plaquebildung als auch zur Reduktion der Gingivitis. 134 erwachsene Probanden beendeten die 2 Wochen dauernde Studie mit experimenteller Gingivitis. Nach der Erstuntersuchung, die die Erhebung des Plaque Index, des Modifizierten Gingival Index und des Gingivalen Blutungs Index umfasste, erhielten die Probanden eine professionelle Zahnreinigung. Den Probanden wurden randomisiert 3 Spüllösungen zugewiesen (Hexitidin 0,1%, Chlorhexidin 0,12% [positive Kontrolle] oder ein 5%iger Hydroalkohol [negative Kontrolle]) und begannen damit als alleinige Mundhygienemaßnahme 3 mal täglich unter Aufsicht zu spülen. Nach 2 Wochen wurden die Indizes erneut erhoben. Ergebnisse: Im Vergleich zur negativen Kontrolle zeigte die Hexitidin-Gruppe eine statistisch signifikante Hemmung und Reduktion der supragingivalen Plaque und gingivalen Entzündung mit Reduktionen von 6,3%, 33,5% bzw. 56% für Gingivitis, Plaque bzw. gingivale Blutung. Die Ergebnisse der Chlorhexidin-Gruppe dienten zur Validierung der Studie. Schlussfolgerung: Diese Studie bestätigt die Wirksamkeit von Hexitidin zur Reduktion supragingivaler Plaque und gingivaler Entzündung. Résumé Cette étude clinique contrôlée par groupe parallèle avec examinateur aveugle a estimé l'efficacité d'un bain de bouche à 0,1% d'héxatidine tant à inhiber le développement de la plaque sus-gingivale qu'à réduire la gingivite. Cent trente-quatre adultes ont achevé un gingivite expérimentale de deux semaines. A la suite de l'examen de base comprenant l'indice de plaque, l'indice gingival modifié et l'indice de saignement gingival, les sujets ont reçu une prophylaxie dentaire complète. Ils ont ensuite été répartis de manière randomisée pour utiliser un des trois bains de bouche suivants : héxatidine 0,1%, chlorhexidine 0,12% (contrôle positif) ou l'hydroalcool 5% (contrôle négatif), et ont commencé a effectuer un rinçage supervisé trois fois par jour comme unique méthode d'hygiène buccale. Tous les indices ont été relevés après deux semaines. Comparé au groupe négatif le groupe héxatidine montrait une inhibition et une réduction significatives de la plaque sus-gingivale et de l'inflammation gingivale avec des réductions respectives de 6,3, 33,5 et 56% pour la gingivite, la plaque dentaire et le saignement gingival. Les résultats du groupe chlorhexidine ont été utilisés pour valider cette étude. Celle-ci confirme l'efficacité de l'héxatidine à réduire la plaque dentaire sus-gingivale et l'inflammation gingivale. [source] Non-specific immune response of turbot, Scophthalmus maximus (L.), experimentally infected with a pathogenic Vibrio pelagiusJOURNAL OF FISH DISEASES, Issue 6 2003L Villamil Abstract The effect of a pathogenic Vibrio pelagius, isolated during a mass mortality of turbot larvae, on the non-specific immune response of turbot, Scophthalmus maximus (L.), macrophages was studied both in vitro and in vivo. The in vitro treatment of head kidney (HK) macrophages with viable V. pelagius caused a significant inhibition of the chemiluminescence (CL) response in comparison with untreated macrophages, while incubation with heat-killed bacteria did not affect this response. In vivo, the intraperitoneal injection of V. pelagius resulted in a significant inhibition of the CL response in infected fish at days 1 and 4 post-infection compared with the control fish response. The HK macrophage nitric oxide (NO) production was enhanced by in vitro incubation with intermediate doses of viable V. pelagius (5 × 103 and 5 × 104 bacteria mL,1) and higher doses of the heat-killed bacteria (5 × 104,5 × 106 bacteria mL,1). In both cases, the NO inhibitorN- , -nitro-L-arginine was capable of down-regulating the specific NO induction caused by incubation with the bacterial treatments. In contrast, incubation with ECPs at higher doses caused a reduction in NO production. In vivo, a significant enhancement in NO production was also observed in macrophage supernatants at day 10 post-infection. Lysozyme concentration in the serum was also significantly increased in the experimentally infected fish at days 4 and 10 post-injection. In addition, viable V. pelagius and its ECPs significantly reduced HK macrophage viability in vitro, whereas no significant differences in viability were observed during the incubation with heat-killed bacteria. As NO production was enhanced in the experimentally infected fish, the inhibitory effect of the NO donor, S-nitroso-acetyl-penicillamine (SNAP), was tested in vitro in a cell-free assay. The results showed that growth of V. pelagius was significantly inhibited using SNAP at a high concentration (1 mm). [source] LISTERIA MONOCYTOGENES AND ESCHERICHIA COLI O157:H7 INHIBITION IN VITRO BY LIPOSOME-ENCAPSULATED NISIN AND ETHYLENE DIAMINETETRAACETIC ACIDJOURNAL OF FOOD SAFETY, Issue 2 2008T. MATTHEW TAYLOR ABSTRACT Encapsulation technologies that effectively reduce antimicrobial interaction with food components or protect antimicrobial compounds from food processing measures have the potential to improve the microbiological safety of ready-to-eat foods. Recent application of liposomes for the preservation of cheese has spurred research into their utility in other food matrices. To ascertain the feasibility of encapsulated antimicrobial for the control of Listeria monocytogenes and Escherichia coli O157:H7 growth in a model system, nisin (5.0 and 10.0 µg/mL) and the chelator ethylene diaminetetraacetic acid were entrapped in phospholipid liposomes. While phosphatidylcholine (PC) liposomes did not produce significant inhibition of target pathogens, PC/phosphatidylglycerol 8/2 and 6/4 (mol%) produced significant inhibition of pathogens. Near-complete inhibition of E. coli O157:H7 with liposomal antimicrobials at concentrations below those reported necessary for unencapsulated antimicrobial and chelator suggests that liposomes may represent a powerful technology for the encapsulation of antimicrobials and the control of foodborne pathogens. PRACTICAL APPLICATIONS The activity of many antimicrobials is abolished in many food products for a variety of reasons. Interference and cross-reactions of the antimicrobial and various food constituents, such as protein and fat, are difficult to overcome and often require large amounts of antimicrobial in order to gain significant reductions in the pathogen load in a product. Loss of solubility of some antimicrobials based on pH or ionic strength will negatively affect the antimicrobial potential of a compound like nisin. Liposome encapsulation technologies, such as that reported here, may allow for the maintenance of antimicrobial activity by protecting the antimicrobial against cross-reactions with food components. Additionally, the liposome core represents a microenvironment which can be manipulated by the manufacturer in order to preserve optimal antimicrobial solubility and stability conditions until the time of release. [source] | ||||||||||||||||||||||||||||||||||||||||