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Vitro Activity (vitro + activity)
Selected Abstractso-Carboranyl Derivatives of 1,3,5-s-Triazines: Structures, Properties and in vitro Activities.CHEMINFORM, Issue 32 2003Chai-Ho Lee No abstract is available for this article. [source] Synthesis and in vitro Activity of Novel Isoxazolyl Tetrahydropyridinyl Oxazolidinone Antibacterial Agents.CHEMINFORM, Issue 9 2004Jae Seok Lee Abstract For Abstract see ChemInform Abstract in Full Text. [source] In vitro study on the anticandidal activity of Melaleuca alternifolia (tea tree) essential oil combined with chitosanFLAVOUR AND FRAGRANCE JOURNAL, Issue 4 2008Claudia Juliano Abstract The in vitro activities of commercial Melaleuca alternifolia essential oil (tea tree oil; TTO) and chitosan were investigated against Candida albicans, both alone and in combination, to assess their potential synergistic action; their anticandidal properties were assessed using standard microbiological techniques, such as MIC evaluation and a ,time,kill' test. Our results demonstrated that both TTO and chitosan possess remarkable activity against Candida: TTO inhibited C. albicans at 0.5 % v/v and was able to kill yeast cells in 120,min at 1% and in 300 min at 0.5,0.25%; as far as chitosan was concerned, 0.5 mg/ml were required to inhibit Candida growth in liquid medium, whereas 0.5,2 mg/ml chitosan required 24 h to kill them in the ,time,kill' test; this effect was pH-dependent, being present at pH 5.0 and disappearing at pH 2.0. When TTO and chitosan were tested together, the polymer reduced the MIC of TTO but did not enhance the activity of the oil as evaluated in the ,time,kill' test. Copyright © 2008 John Wiley & Sons, Ltd. [source] Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing abilityINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Ying-Yi Li Abstract We previously demonstrated that Pim-3, a protooncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not in normal tissues of endoderm-derived organs, including pancreas, liver, colon and stomach. Moreover, aberrantly expressed Pim-3 can prevent tumor cell apoptosis by inactivating a proapoptotic molecule, Bad, and enhancing the expression of an antiapoptotic molecule, Bcl-XL. These observations prompted us to speculate that a chemical targeting Pim-3 kinase may be a good candidate for a novel type of anticancer drug. Hence, we screened various low-molecule compounds by examining their capacity to inhibit Pim-3 kinase activity in vitro. We observed that some synthetic intermediates of stemonamide can inhibit in vitro activities of Pim-3 kinase and its related kinases, such as Pim-1 and Pim-2. Moreover, these compounds inhibit in vitro cell proliferation of various human pancreatic, hepatocellular and colon cancer cell lines. Furthermore, the compounds can induce apoptosis of human pancreatic cancer cell lines in vitro by reducing the amount of phospho-Ser112 -Bad, but not total amounts of Bad and Pim-3. Finally, when the compound was administered to nude mice injected with a human pancreatic cancer cell line, it retarded tumor growth by increasing apoptotic cell numbers and decreasing proliferating cell numbers without causing serious adverse effects on blood counts. These observations indicate that the chemicals and its related compounds may be effective for the treatment of tumors of endoderm-derived organs, particularly the pancreas. [source] A new, broad-spectrum azole antifungal: posaconazole , mechanisms of action and resistance, spectrum of activityMYCOSES, Issue 2006H. Hof Summary Posaconazole, a new triazole antifungal, exerts principally the same mechanism of action as the other azole derivatives, i.e. it inhibits the ergosterol production by binding and inhibiting the lanosterol-14,-demethylase which is present in almost all fungi except Pneumocystis and Pythium. Posaconazole has an exquisitely high affinity to this target. Since posaconazole has a chemical structure different from fluconazole and voriconazole, it can interact with an additional domain of the target so that it may inhibit even mutated strains resistant to fluconazole and voriconazole. In addition posaconazole is a bad substrate for efflux pumps in fungi, so it can stay active when other azoles are already inactive. Furthermore, the spectrum of posaconazole is rather large including also some zygomycetes resistant to other azoles. In conclusion, posaconazole is actually the most potent azole derivative used in medicine. A combination of posaconazole with other groups of antifungals may have a favourable effect. There are several methods to test the in vitro activities of posaconazole including the E-test, though interpretive breakpoints are still lacking. [source] Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinonesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 3 2002Philip J Jewess Abstract The main mode of herbicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones is shown to be inhibition of photosystem II (PSII). The herbicidal and in vitro activities have been measured and correlated with their (Log)octanol/water partition coefficients (Log Ko/w). The length of the 3- n -alkyl substituent for optimal activity differed between herbicidal and in vitro activity. The maximum in vitro activity was given by the nonyl to dodecyl homologues (Log Ko/w between 6.54 and 8.12), whereas herbicidal activity peaked with the n -hexyl compound (Log Ko/w,=,4.95). The effect of chain branching was also investigated using isomeric pentyl analogues substituted at position 3. All exhibited similar levels of in vitro activities but herbicidal activities differed, albeit moderately, with the exception of one analogue that was much less phytotoxic. Other modes of action were also investigated using two representative compounds. They did not show any activity on photosystem I or mitochondrial complex I, or generate toxic oxygen radicals by redox cycling reactions. Only moderate activity was found against mitochondrial complex III from plants, in contrast to much higher corresponding activity using an insect enzyme. © 2002 Society of Chemical Industry [source] Insecticidal 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activityPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 3 2002Philip J Jewess Abstract The insecticidal and in vitro activities of four homologous series of 2-hydroxy and acetoxy-3-substituted-1,4-naphthoquinones have been measured and correlated with their (Log) octanol/water partition coefficients (Log Ko/w). In vitro activity against mitochondrial complex III was only exhibited by 2-hydroxy-3-alkyl-1,4-naphthoquinones, indicating that the 2-acetoxy compounds act as pro-insecticides. Good correlation was observed between in vivo activity against the two-spotted spider mite, Tetranychus urticae and inhibition of complex III isolated from blowfly flight muscle. Both hydroxy and acetoxy analogues of individual compounds exhibited similar levels of in vivo activity with optimum activity for analogues with Log Ko/w values of 7,8. In contrast, the acetoxy derivatives showed superior in vivo activity against the tobacco whitefly, Bemisia tabaci. Complex III isolated from whitefly was optimally inhibited by hydroxy analogues with lower Log Ko/w values (6.0,6.5) and was also more sensitive than the blowfly enzyme to all the compounds tested. © 2002 Society of Chemical Industry [source] In vivo and in vitro activities of the seed extract of Piper guineense Schum. and Thonn. against skin and gill monogenean parasites of gold,sh (Carassius auratus auratus)PHYTOTHERAPY RESEARCH, Issue 10 2004A. P. Ekanem Abstract Methanol extracts of the seeds of Piper guineense (Piperaceae) were active against gold,sh (Carassius auratus auratus L. Pisces Cyprinidae) monogenean parasites. The seed extract of P. guineense was administered at different concentrations (0.5,2.0 mg/L) under in vivo and in vitro conditions. There was a higher ef,cacy of the effects of the extracts against ,sh parasites under in vitro situations than under in vivo. Three major compounds (piperanine, N -isobutyl (E,E)-2,4 decadienamide and ,,,, -dihydrowasanine) were identi,ed from the seed extract of Piper guineense by LC-MS analysis. Copyright © 2004 John Wiley & Sons, Ltd. [source] Review: Organotin compounds and their therapeutic potential: a report from the Organometallic Chemistry Department of the Free University of Brussels,APPLIED ORGANOMETALLIC CHEMISTRY, Issue 9 2002Marcel Gielen Abstract An overview of the development of antitumour organotin derivatives is presented and discussed for selected classes of compounds, such as tetraorganodicarboxylatodistannoxanes and related diorganotin dicarboxylates, and for triorganotin carboxylates. Among the carboxylate groups used are steroidcarboxylates and other biologically relevant carboxylates. High to very high in vitro activities have been found, sometimes equalling that of doxorubicin. Solubility in water is an important issue, dominating the in vivo testing of compounds. Polar substituents, like fluorine or polyoxaalkyl moieties, improve the water solubility. Although organotin derivatives constitute a separate class of compounds, the comparison with cisplatin is inevitable. Among the observed toxicities, neurotoxicity, known from platinum cytostatics, and gastrointestinal toxicity, typical for many oncology drugs, have been detected, but to a lower extent. Further research to develop novel useful organotin antitumour compounds needs to be carried out. Copyright © 2002 John Wiley & Sons, Ltd. [source] Novel natural parabens produced by a Microbulbifer bacterium in its calcareous sponge host Leuconia niveaENVIRONMENTAL MICROBIOLOGY, Issue 6 2009Elodie Quévrain Summary A broad variety of natural parabens, including four novel structures and known ethyl and butyl parabens, were obtained from culture of a Microbulbifer sp. bacterial strain isolated from the temperate calcareous marine sponge Leuconia nivea (Grant 1826). Their structures were elucidated from spectral analysis, including mass spectrometry and 1D and 2D nuclear magnetic resonance. Their antimicrobial activity evaluated against Staphylococcus aureus was characterized by much higher in vitro activity of these natural paraben compounds 3,9 than commercial synthetic methyl and propyl parabens, usually used as antimicrobial preservatives. Compounds 4 and 9 revealed a bacteriostatic effect and compounds 6 and 7 appeared as bactericidal compounds. Major paraben compound 6 was also active against Gram positive Bacillus sp. and Planococcus sp. sponge isolates and was detected in whole sponge extracts during all seasons, showing its persistent in situ production within the sponge. Moreover, Microbulbifer sp. bacteria were visualized in the sponge body wall using fluorescence in situ hybridization with a probe specific to L4-n2 phylotypes. Co-detection in the sponge host of both paraben metabolites and Microbulbifer sp. L4-n2 indicates, for the first time, production of natural parabens in a sponge host, which may have an ecological role as chemical mediators. [source] Mechanism of activation of the double-stranded-RNA-dependent protein kinase, PKRFEBS JOURNAL, Issue 13 2001Role of dimerization, cellular localization in the stimulation of PKR phosphorylation of eukaryotic initiation factor-2 (eIF2) An important defense against viral infection involves inhibition of translation by PKR phosphorylation of the , subunit of eIF2. Binding of viral dsRNAs to two dsRNA-binding domains (dsRBDs) in PKR leads to relief of an inhibitory region and activation of eIF2 kinase activity. Interestingly, while deletion of the regulatory region of PKR significantly induces activity in vitro, the truncated kinase does not inhibit translation in vivo, suggesting that these sequences carry out additional functions required for PKR control. To delineate these functions and determine the order of events leading to activation of PKR, we fused truncated PKR to domains of known function and assayed the chimeras for in vivo activity. We found that fusion of a heterologous dimerization domain with the PKR catalytic domain enhanced autophosphorylation and eIF2 kinase function in vivo. The dsRBDs also mediate ribosome association and we proposed that such targeting increases the localized concentration of PKR, enhancing interaction between PKR molecules. We addressed this premise by linking the truncated PKR to RAS sequences mediating farnesylation and membrane localization and found that the fusion protein was functional in vivo. These results indicate that cellular localization along with oligomerization enhances interaction between PKR molecules. Alanine substitution for the phosphorylation site, threonine 446, impeded in vivo and in vitro activity of the PKR fusion proteins, while aspartate or glutamate substitutions partially restored the function of the truncated kinase. These results indicate that both dimerization and cellular localization play a role in transient protein,protein interactions and that trans -autophosphorylation is the final step in the mechanism of activation of PKR. [source] VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like mannerGENES TO CELLS, Issue 7 2003Tomoyuki Fukuda Background: Inteins and group I introns found in prokaryotic and eukaryotic organisms occasionally behave as mobile genetic elements. During meiosis of the yeast Saccharomyces cerevisiae, the site-specific endonuclease encoded by VMA1 intein, VDE, triggers a single double-strand break (DSB) at an inteinless allele, leading to VMA1 intein homing. Besides the accumulating information on the in vitro activity of VDE, very little has been known about the molecular mechanism of intein homing in yeast nucleus. Results: We developed an assay to detect the product of VMA1 intein homing in yeast genome. We analysed mutant phenotypes of RecA homologs, Rad51p and Dmc1p, and their interacting proteins, Rad54p and Tid1p, and found that they all play critical roles in intein inheritance. The absence of DSB end processing proteins, Sae2p and those in the Mre11-Rad50-Xrs2 complex, also causes partial reduction in homing efficiency. As with meiotic recombination, crossover events are frequently observed during intein homing. We also observed that the absence of premeiotic DNA replication caused by hydroxyurea (HU) or clb5, clb6, mutation reduces VDE-mediated DSBs. Conclusion: The repairing system working in intein homing shares molecular machinery with meiotic recombination induced by Spo11p. Moreover, like Spo11p-induced DNA cleavage, premeiotic DNA replication is a prerequisite for a VDE-induced DSB. VMA1 intein thus utilizes several host factors involved in meiotic and recombinational processes to spread its genetic information and guarantee its progeny through establishment of a parasitic relationship with the organism. [source] Characterization of specific egg yolk immunoglobulin (IgY) against mastitis - causing Staphylococcus aureusJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2008Y.-H. Zhen Abstract Aims:, To evaluate the in vitro activity of egg yolk immunoglobulin (IgY) against mastitis-causing Staphylococcus aureus. Methods and Results:, Specific IgY was produced by immunizing hens with formaldehyde-killed Staph. aureus, using a bacterial strain known to cause mastitis. The IgY, of 94% purity, was obtained from yolks by water dilution, salt precipitations, ultrafiltration and gel filtration. ELISA indicated that the IgY produced was specific to the antigen and five Staph. aureus isolates obtained from mastitic cows. The growth of Staph. aureus was inhibited by specific IgY at concentrations from 1 to 10 mg ml,1 in a dose-dependent manner. The phagocytosis of Staph. aureus by milk macrophages was enhanced in the presence of specific IgY with the highest phagocytic percentage being 30% higher than that without IgY (P < 0·05). Conclusions:, The specific IgY against mastitis-causing Staph. aureus inhibited the growth of Staph. aureus and enhanced the phagocytosis of Staph. aureus by milk macrophages. Significance and Impact of the Study:, Specific IgY would be a potential treatment for bovine mastitis. [source] Activity and mode of action against fungal phytopathogens of bovine lactoferricin-derived peptidesJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2006A. Muñoz Abstract Aim:, To evaluate the activity against fungal phytopathogens of two synthetic peptides derived from the protein bovine lactoferricin: the antibacterial active core of six amino acid residues (LfcinB20,25) and an extension of 15 amino acids (LfcinB17,31). Methods and Results:,In vitro activity against fungal pathogens was determined and compared with that against model micro-organisms. Activity was demonstrated against fungi of agronomic relevance. Distinct antimicrobial properties in vitro were found for the two peptides. LfcinB17,31 had growth inhibitory activity higher than LfcinB20,25. However, LfcinB17,31 was not fungicidal to quiescent conidia of Penicillium digitatum at the concentrations assayed, while LfcinB20,25 killed conidia more efficiently. Microscopical observations showed that the mycelium of P. digitatum treated with LfcinB17,31 developed alterations of growth, sporulation and chitin deposition, and permeation of hyphal cells. In experimental inoculations of mandarins, both peptides showed limited protective effect against the disease caused by P. digitatum. Conclusions:, LfcinB20,25 and LfcinB17,31 peptides were shown to have antimicrobial activity against plant pathogenic filamentous fungi, with distinct properties and mode of action. Significance and Impact of the Study:, LfcinB20,25 and LfcinB17,31 peptides offer novel alternatives to develop resistant plants by molecular breeding. [source] Commensal bacilli inhibitory to mastitis pathogens isolated from the udder microbiota of healthy cowsJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2006M. Al-Qumber Abstract Aims:, To isolate from the microbiota of the healthy cow udder commensal bacteria having antimicrobial activity against bovine mastitis pathogens, with a long-term view to their potential application as antimastitis probiotics. Methods and Results:, Bacterial isolates from four healthy cow udders were tested for inhibitory activity against three Gram-positive indicator bacteria. This led to the selection of nine broadly inhibitory strains. All were of the Bacillus genus and their antimicrobial activities, which appeared heterogeneous on the basis of their antibacterial spectra and heat susceptibilities, enabled grouping of the inhibitory bacilli into six different inhibitory profiles. All displayed strong in vitro activity against Gram-positive mastitis pathogens. Inhibitory bacilli were recovered from each of the 11 udder samples collected over 7 months from one of these cows and the isolates included representatives of all six inhibitory profiles. Conclusions:, Bacilli present in the udder microbiota of healthy cows can produce a variety of broadly active inhibitors of Gram-positive bacteria, including potential mastitis pathogens. Significance and Impact of the Study:, Inhibitor-producing strains of commensal Bacillus species have been identified, which may have the potential for use as possible antimastitis probiotics. [source] Inhalation efficacy of RFI-641 in an African green monkey model of RSV infectionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2003W.J. Weiss Abstract: Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73,1.34 PFU/ml (P -value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection. [source] Effect of benzyl isothiocyanate on tomato fruit infection development by Alternaria alternataJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2005R Troncoso-Rojas Abstract Benzyl isothiocyanate (BITC) is known to be a strong antifungal compound in vitro against different fungi. The effectiveness of benzyl isothiocyanate to control Alternaria alternata growth in vitro and in vivo was tested. BITC in vitro activity was evaluated in A alternata growing on potato dextrose agar and exposed to 0.025, 0.05, 0.1, 0.2 or 0.4 mg ml,1. In vivo activity was evaluated by exposing A alternata -inoculated tomato fruits for either 18 or 36 h to 0.28 or 0.56 mg ml,1 BITC packed on low-density polyethylene film (LDPF) bags. Additionally, the effect of BITC on post-harvest physiology and tomato quality throughout storage at 20 °C was evaluated daily by monitoring respiration rate and ethylene production, whereas total soluble solids, pH, titratable acidity and fresh weight loss were measured every 3 days. Results showed that the minimal inhibitory concentration of BITC in vitro was 0.1 mg ml,1. A combined use of 0.56 mg ml,1 BITC with LDPF for 18 h was the optimum treatment to control Alternaria rot in packed tomato fruit. No effect of BITC on respiration rate, ethylene production, total soluble solids, pH, weight loss and titratable acidity was observed. Results suggest that BITC can be used as a post-harvest treatment to control Alternaria rot in tomato fruit without detrimental effects on the tomato post-harvest quality. Copyright © 2005 Society of Chemical Industry [source] Identification of key residues involved in mediating the in vivo anti-tumor/anti-endothelial activity of AlphastatinJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007C. A. STATON Summary., Background :,We have recently shown that Alphastatin, a 24-amino-acid peptide (ADSGEGDFLAEGGGVRGPRVVERH) derived from human fibrinogen has anti-endothelial properties in vitro and in vivo. Objectives:, The aim of this study was to determine the activity of a terminally modified (stabilized) form of Alphastatin in vitro and in vivo and to identify the key residues required for this activity. Methods:, The in vitro activity of modified Alphastatin, truncates and mutants was determined by endothelial cell (HuDMEC) tubule formation and migration. Active peptides were then assessed in vivo using syngeneic murine subcutaneous 4T1 mammary carcinomas. Results:, Modified Alphastatin-inhibited HuDMEC migration and tubule formation in response to multiple growth factors and caused a 45% inhibition in tumor growth when administered intravenously at 0.25 mg kg,1 (three times per week). Intravenous (i.v.) administration proved non-toxic at all doses investigated, whereas oral and intraperitoneal (i.p.) administration demonstrated neither anti-tumor activity nor toxicity. Truncations of Alphastatin revealed an 11-amino-acid peptide (DFLAEGGGVRG), termed AHN419, which inhibited endothelial cell activity in vitro; however, intravenous AHN419 caused a non-significant growth inhibition in vivo. Single amino acid substitutions to alanine along the entire length of Alphastatin indicated that additional residues outside the AHN419 sequence were required for full activity. Conclusions:, Terminal modification of Alphastatin altered the in vivo efficacy and these studies suggest that a hydrophobic cluster (Phe8, Leu9, Ala10 and Val15) is essential for the biological activity, but additional residues, including Ser3-Gly14, Pro18-Val20 and Arg23 are required for full inhibitory activity of Alphastatin. [source] IN FOCUS: Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparinJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2005M. M. PRECHEL Summary., The serotonin release assay (SRA) tests for antibodies responsible for heparin-induced thrombocytopenia (HIT). By definition, SRA-positive antibodies cause platelet serotonin release in vitro, in the presence of low concentrations of heparin, but not with excess heparin. Many SRA-positive sera activate platelets in the presence of saline without drug, either as a result of residual heparin in the specimen, or because of intrinsic features of the HIT antibodies. The present experiments show that neither exhaustive heparinase treatment, nor chromatographic removal of heparin abrogates the spontaneous platelet activation caused by these HIT antibodies. This is the first study to systematically demonstrate that in vitro activity of HIT antibodies can be independent of heparin. In addition, T-gel chromatography demonstrated differences among fractions of enzyme-linked-immunosorbent assay (ELISA)-positive HIT antibodies within individual specimens. Certain ELISA-positive fractions had SRA activity while others did not, and the SRA activity was not proportional to HIT antibody ELISA titer. These data suggest that antibodies formed as a result of heparin treatment are heterogeneous, and that some can contribute to the pathogenesis of HIT even when heparin is no longer present. [source] Determination of the In Vitro Susceptibility of Feline Tritrichomonas foetus to 5 Antimicrobial AgentsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2007Elizabeth J. Kather Background: The nitroimidazole, ronidazole, has been demonstrated to have in vitro and in vivo activity against the protozoan Tritrichomonas foetus in cats. The purpose of this study was to evaluate the in vitro susceptibility of feline T foetus isolates obtained from naturally infected cats to 5 antimicrobial agents and to compare the in vitro time kill of ronidazole and metronidazole. Hypothesis: We hypothesized that nitroimidazoles have in vitro activity against T foetus, whereas furazolidone, omeprazole, and paromomycin do not. Animals: Fecal specimens were cultured from 4 naturally infected Bengal cats with a history of T foetus -associated diarrhea. Methods: A 24-hour susceptibility assay was performed on all 4 isolates for the 5 antimicrobial agents. A time-kill microdilution method was performed on 2 isolates for metronidazole and ronidazole. Results: Paromomycin and omeprazole showed no in vitro effect at concentrations ±80 ,g/mL. There was no significant difference in 24-hour susceptibilities among metronidazole, ronidazole, and furazolidone. In addition, only the results of the highest concentration tested (80 ,g/mL) and concentrations of 1.25 and 2.5 ,g/mL revealed significant differences in the rate of trophozoite killing, with ronidazole having a faster reduction in trophozoite survival. Conclusions and Clinical Importance: Time-kill assays demonstrated ronidazole had a higher lethal activity compared with metronidazole. These findings contrast with a previously published report and may reflect strain variation, different methodologies, or both. The lack of clinical response seen with metronidazole administration to treat feline trichomoniasis may not reflect inherent resistance but rather in vivo events involving drug distribution and pharmacokinetics. [source] Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolatesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010L. H. JAVSICAS Javsicas, LH., Giguère, S., Womble, AY. Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01151.x. The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6,10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean ± SD time to peak serum telithromycin activity (Tmax) was 1.75 ± 0.76 h, maximum serum activity (Cmax) was 1.43 ± 0.37 ,g/mL, and terminal half-life (t½) was 3.81 ± 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 ± 14.5 ,g/mL) than in PELF (5.07 ± 2.64 ,g/mL), and plasma (0.84 ± 0.25 ,g/mL). The MIC90 of telithromycin for macrolide-resistant R. equi isolates (8 ,g/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 ,g/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC50 = 4.0 ,g/mL) was significantly lower than that of clarithromycin (MIC50 = 24.0 ,g/mL), azithromycin (MIC50 =256 ,g/mL) and erythromycin (MIC50 = 24 ,g/mL). [source] Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2002E. HEINEN The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 ,g/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t½) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration,time curve of the 24-h dosing interval (AUC0,24) for marbofloxacin and orbifloxacin were similar (approximately 13 ,g · h/mL), enrofloxacin attained an AUC0,24 of 8.7 and difloxacin of 9.3 ,g · h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as Cmax/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC0,24/MIC (area under the 24-h serum concentration,time curve/minimum inhibitory concentration) compared with other FQs. [source] Antifungal activity of Pterocaulon alopecuroides (Asteraceae) against chromoblastomycosis agentsMYCOSES, Issue 3 2010Tatiane Caroline Daboit Summary Plants of the genus Pterocaulon (Asteraceae) are popularly used in the treatment of skin diseases caused by fungi and bacteria. The aim of this work was to investigate the in vitro activity of the crude methanolic extract obtained from the aerial parts of Pterocaulon alopecuroides (Lam.) against some agents of chromoblastomycosis, a chronic fungal infection of the skin and of the subcutaneous tissue caused by traumatic inoculation of the aetiological agent. The extract was active against all the strains tested showing a minimum inhibitory concentration between 625 and 2500 ,g ml,1. The assessment of fungistatic/fungicidal activity demonstrated that the extract was fungistatic against Fonsecaea spp. and fungicidal against all the other fungi. Our results indicate that the identification of bioactive components present in the crude methanolic extract of P. alopecuroides against chromoblastomycosis agents can be an important strategy to manage this mycosis in the future. [source] TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Vijay Ramakrishnan Interaction of myeloma cells with the bone marrow microenvironment is mediated in large part through different cytokines, especially VEGF and IL6. These cytokines, especially IL6, leads to upregulation of the JAK/STAT pathway in myeloma cell, contributing to increased proliferation, decreased apoptosis, and acquired drug resistance. Here, we examined the preclinical activity of a novel JAK2 inhibitor TG101209. TG101209 induced dose- and time-dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient-derived plasma cells. Evaluation of U266 cell lines and patient cells, which have a mix of CD45 positive and negative cells, demonstrated more profound cytotoxicity and antiproliferative activity of the drug on the CD45+ population relative to the CD45, cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl-xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209, when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells. Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinonesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 3 2002Philip J Jewess Abstract The main mode of herbicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones is shown to be inhibition of photosystem II (PSII). The herbicidal and in vitro activities have been measured and correlated with their (Log)octanol/water partition coefficients (Log Ko/w). The length of the 3- n -alkyl substituent for optimal activity differed between herbicidal and in vitro activity. The maximum in vitro activity was given by the nonyl to dodecyl homologues (Log Ko/w between 6.54 and 8.12), whereas herbicidal activity peaked with the n -hexyl compound (Log Ko/w,=,4.95). The effect of chain branching was also investigated using isomeric pentyl analogues substituted at position 3. All exhibited similar levels of in vitro activities but herbicidal activities differed, albeit moderately, with the exception of one analogue that was much less phytotoxic. Other modes of action were also investigated using two representative compounds. They did not show any activity on photosystem I or mitochondrial complex I, or generate toxic oxygen radicals by redox cycling reactions. Only moderate activity was found against mitochondrial complex III from plants, in contrast to much higher corresponding activity using an insect enzyme. © 2002 Society of Chemical Industry [source] Insecticidal 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activityPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 3 2002Philip J Jewess Abstract The insecticidal and in vitro activities of four homologous series of 2-hydroxy and acetoxy-3-substituted-1,4-naphthoquinones have been measured and correlated with their (Log) octanol/water partition coefficients (Log Ko/w). In vitro activity against mitochondrial complex III was only exhibited by 2-hydroxy-3-alkyl-1,4-naphthoquinones, indicating that the 2-acetoxy compounds act as pro-insecticides. Good correlation was observed between in vivo activity against the two-spotted spider mite, Tetranychus urticae and inhibition of complex III isolated from blowfly flight muscle. Both hydroxy and acetoxy analogues of individual compounds exhibited similar levels of in vivo activity with optimum activity for analogues with Log Ko/w values of 7,8. In contrast, the acetoxy derivatives showed superior in vivo activity against the tobacco whitefly, Bemisia tabaci. Complex III isolated from whitefly was optimally inhibited by hydroxy analogues with lower Log Ko/w values (6.0,6.5) and was also more sensitive than the blowfly enzyme to all the compounds tested. © 2002 Society of Chemical Industry [source] Increase in activity, glycosylation and expression of cytokinin oxidase/dehydrogenase during the senescence of barley leaf segments in the darkPHYSIOLOGIA PLANTARUM, Issue 4 2007Klaus Conrad The aim of the study was to elucidate relations between senescence and cytokinin oxidase/dehydrogenase (CKX, EC 1.4.3.18/1.5.99.12). Segments derived from first foliage leaves of Hordeum vulgare L. cv. Alexis were put with their bases into water and kept in darkness. Their senescence was characterized, e.g. by a 60% decline in chlorophyll within 5 days. During this time, the in vitro activity of CKX increased fast and markedly, e.g. 14-fold. Application of 10,4M kinetin (Kin), which slightly retarded the loss of chlorophyll, multiplied the enhancement of CKX activity strongly. Both in the presence and in the absence of Kin, the proportion of glycosylated to non-glycosylated CKX increased during senescence. By hybridization with an antisense RNA probe derived from a fragment of the CKX gene Zmckx1 of maize, an increase of the corresponding transcript of the barley gene Hvckx1 in segments incubated without Kin was shown. The content of base and riboside cytokinins slowly declined in such segments, which argues against triggering but for facilitating senescence processes by CKX. [source] HPLC isolation of the anti-plasmodially active bisbenzylisoquinone alkaloids present in roots of Cissampelos mucronataPHYTOCHEMICAL ANALYSIS, Issue 1 2003Jeannette Ndaya Tshibangu Abstract The methanolic extract of dried, powdered Cissampelos mucronata roots possesses significant in vitro activity against Plasmodium falciparum. In order to enable further pharmacological testing, the substances responsible for the observed activity were purified, mainly by HPLC, using various stationary and mobile phases. The active principles were determined to be a series of bisbenzylisoquinoline alkaloids, a group of natural products for which one of the first routine preparative HPLC separation methods is described. Copyright © 2003 John Wiley & Sons, Ltd. [source] Low-temperature photosynthetic performance of a C4 grass and a co-occurring C3 grass native to high latitudesPLANT CELL & ENVIRONMENT, Issue 7 2004D. S. KUBIEN ABSTRACT The photosynthetic performance of C4 plants is generally inferior to that of C3 species at low temperatures, but the reasons for this are unclear. The present study investigated the hypothesis that the capacity of Rubisco, which largely reflects Rubisco content, limits C4 photosynthesis at suboptimal temperatures. Photosynthetic gas exchange, chlorophyll a fluorescence, and the in vitro activity of Rubisco between 5 and 35 °C were measured to examine the nature of the low-temperature photosynthetic performance of the co-occurring high latitude grasses, Muhlenbergia glomerata (C4) and Calamogrostis canadensis (C3). Plants were grown under cool (14/10 °C) and warm (26/22 °C) temperature regimes to examine whether acclimation to cool temperature alters patterns of photosynthetic limitation. Low-temperature acclimation reduced photosynthetic rates in both species. The catalytic site concentration of Rubisco was approximately 5.0 and 20 µmol m,2 in M. glomerata and C. canadensis, respectively, regardless of growth temperature. In both species, in vivo electron transport rates below the thermal optimum exceeded what was necessary to support photosynthesis. In warm-grown C. canadensis, the photosynthesis rate below 15 °C was unaffected by a 90% reduction in O2 content, indicating photosynthetic capacity was limited by the capacity of Pi -regeneration. By contrast, the rate of photosynthesis in C. canadensis plants grown at the cooler temperatures was stimulated 20,30% by O2 reduction, indicating the Pi -regeneration limitation was removed during low-temperature acclimation. In M. glomerata, in vitro Rubisco activity and gross CO2 assimilation rate were equivalent below 25 °C, indicating that the capacity of the enzyme is a major rate limiting step during C4 photosynthesis at cool temperatures. [source] The biochemistry and biology of extracellular plant lipid-transfer proteins (LTPs)PROTEIN SCIENCE, Issue 2 2008Trevor H. Yeats Abstract Plant lipid-transfer proteins (LTPs) are abundant, small, lipid binding proteins that are capable of exchanging lipids between membranes in vitro. Despite their name, a role in intracellular lipid transport is considered unlikely, based on their extracellular localization. A number of other biological roles, including antimicrobial defense, signaling, and cell wall loosening, have been proposed, but conclusive evidence is generally lacking, and these functions are not well correlated with in vitro activity or structure. A survey of sequenced plant genomes suggests that the two biochemically characterized families of LTPs are phylogenetically restricted to seed plants and are present as substantial gene families. This review aims to summarize the current understanding of LTP biochemistry, as well as the evidence supporting the proposed in vivo roles of these proteins within the emerging post-genomic framework. [source] | ||||||||||||||||