Home About us Contact
|
Home About us Contact | ||
|
|
||
Transient Formation (transient + formation)
Selected AbstractsLung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregatesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2009Rui Yang Abstract Chitosan-modified paclitaxel-loaded poly lactic- co -glycolic acid (PLGA) nanoparticles with a mean diameter of 200,300 nm in distilled water were prepared by a solvent evaporation method. The mean diameter increased dramatically in contact with the mouse (CDF1) plasma, as a function of chitosan concentration in the modification solution (e.g., 2670.5 nm for 0.7% chitosan-modified nanoparticles, NP3), but reverted to almost its original size (i.e., 350.7 nm for NP3) following 5 min of gentle agitation. The zeta potential of PLGA nanoparticles was changed to positive by the chitosan modification. The in vitro uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell line (A549) were significantly increased by the modification. Most importantly, a lung-specific increase in the distribution index of paclitaxel (i.e., AUClung/AUCplasma) was observed for chitosan-modified nanoparticles (e.g., 99.9 for NP3 vs. 5.4 for TaxolÔ) when nanoparticles were administered to lung-metastasized mice via the tail vein at a paclitaxel dose of 10 mg/kg. Transient formation of aggregates in the blood stream followed by enhanced trapping in the lung capillaries, and electrical interaction-mediated enhanced uptake across the endothelial cells of the lung tumor capillary appear to be responsible for the lung-tumor-specific distribution of the chitosan modified nanoparticles. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:970,984, 2009 [source] Transient concentration of a ,-tubulin-related protein with a pericentrin-related protein in the formation of basal bodies and flagella during the differentiation of Naegleria gruberiCYTOSKELETON, Issue 2 2002Mi Ra Suh Abstract The distribution of two proteins in Naegleria gruberi, N-,TRP (Naegleria ,-tubulin-related protein) and N-PRP (Naegleria pericentrin-related protein), was examined during the de novo formation of basal bodies and flagella that occurs during the differentiation of N. gruberi. After the initiation of differentiation, N-,TRP and N-PRP began to concentrate at the same site within cells. The percentage of cells with a concentrated region of N-,TRP and N-PRP was maximal (68%) at 40 min when the synthesis of tubulin had just started but no assembled microtubules were visible. When concentrated tubulin became visible (60 min), the region of concentrated N-,TRP and N-PRP was co-localized with the tubulin spot and then flagella began to elongate from the region of concentrated tubulin. When cells had elongated flagella, the concentrated N-,TRP and N-PRP were translocated to the opposite end of the flagellated cells and disappeared. The transient concentration of N-,TRP coincided with the transient formation of an F-actin spot at which N-,TRP and ,-tubulin mRNA were co-localized. The concentration of N-,TRP and formation of the F-actin spot occurred without the formation of microtubules but were inhibited by cytochalasin D. These observations suggest that the regional concentration of N-,TRP and N-PRP is mediated by actin filaments and might provide a site of microtubule nucleation for the assembly of newly synthesized tubulins into basal bodies and flagella. Cell Motil. Cytoskeleton 52:66,81, 2002. © 2002 Wiley-Liss, Inc. [source] The potential for estradiol and ethinylestradiol degradation in english riversENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002Monika D. Jürgens Abstract Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17,-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20°C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 ,g/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions. [source] Pyrene and chrysene fate in surface soil and sand microcosmsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2001J. Chadwick Roper Abstract Polycyclic aromatic hydrocarbons (PAHs) are major components of wastes from municipal gas plants and many wood preservatives. Soil contaminated with these wastes is a potential threat to human health because of the carcinogenicity of many PAHs. This study follows the fate of two four-ring PAHs, pyrene and chrysene, in three matrices: an adapted soil (obtained from a site contaminated with PAHs for more than 75 years), an uncontaminated soil (with and without an inoculum of adapted soil), and sand mixed with an inoculum of adapted soil. Radiolabeled pyrene, chrysene, and salicylic acid (a metabolite of PAH biodegradation) were used to trace the mineralization, transformation, extractability, and formation of an unextractable residual over time. Linear approximations of the rates of these processes were made. High-performance liquid chromatography (HPLC) analysis of extracts from inoculated soil showed the transient formation of two known metabolites: 1-hydroxypyrene (from pyrene) and 1-hydroxy-2-naphthoic acid (from chrysene). The amount of extractable label diminished steadily over the course of the study in systems that were not inhibited with sodium azide, whereas the amount of extractable label remained relatively constant in inhibited systems. Correspondingly, the amount of nonextractable residual label generally increased during each incubation in uninhibited systems, whereas the amount of this residual label remained relatively constant in inhibited systems. In contrast, the rate and extent of mineralization varied widely across matrix types. This suggests that alterations of the PAH that impact extractability and residual formation are common, in contrast to mineralization, which was apparently limited to adapted communities. [source] Specific transcriptional responses induced by 8-methoxypsoralen and UVA in yeastFEMS YEAST RESEARCH, Issue 6 2007Michèle Dardalhon Abstract Treatment of eukaryotic cells with 8-methoxypsoralen plus UVA irradiation (8-MOP/UVA) induces pyrimidine monoadducts and interstrand crosslinks and initiates a cascade of events leading to cytotoxic, mutagenic and carcinogenic responses. Transcriptional activation plays an important part in these responses. Our previous study in Saccharomyces cerevisiae showed that the repair of these lesions involves the transient formation of DNA double-strand breaks and the enhanced expression of landmark DNA damage response genes such as RAD51, RNR2 and DUN1, as well as the Mec1/Rad53 kinase signaling cascade. We have now used DNA microarrays to examine genome-wide transcriptional changes produced after induction of 8-MOP/UVA photolesions. We found that 128 genes were strongly induced and 29 genes strongly repressed. Modifications in gene expression concern numerous biological processes. Compared to other genotoxic treatments, c. 42% of the response genes were specific to 8-MOP/UVA treatment. In addition to common DNA damage response genes and genes induced by environmental stresses, a large fraction of 8-MOP/UVA response genes correspond to membrane-related functions. [source] Kinetics of aerobic and anaerobic oxidations of ethanol by Fenton's reagentINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 9 2008Mordechai L. Kremer For the first time, the time dependence of [H2O2] and [Fe2+] was followed during the aerobic oxidation of ethanol by Fenton's reagent. It was found that part of the ethanol was oxidized by dissolved O2 via the transient formation of H2O2. A model was set up based on FeO2+ as the key intermediate. Both one- and two-equivalent oxidations of ethanol occur, the former producing radical species derived from ethanol. No free radicals derived from H2O2 play part in the system. The relevant rate constants or their ratios were determined. The mechanism accounted successfully also for the anaerobic oxidation of ethanol. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 541,553, 2008 [source] Hsp90: Chaperoning signal transductionJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001Klaus Richter Hsp90 is an ATP dependent molecular chaperone involved in the folding and activation of an unknown number of substrate proteins. These substrate proteins include protein kinases and transcription factors. Consistent with this task, Hsp90 is an essential protein in all eucaryotes. The interaction of Hsp90 with its substrate proteins involves the transient formation of multiprotein complexes with a set of highly conserved partner proteins. The specific function of each component in the processing of substrates is still unknown. Large ATP-dependent conformational changes of Hsp90 occur during the hydrolysis reaction and these changes are thought to drive the chaperone cycle. Natural inhibitors of the ATPase activity, like geldanamycin and radicicol, block the processing of Hsp90 substrate proteins. As many of these substrates are critical elements in signal transduction, Hsp90 seems to introduce an additional level of regulation. © 2001 Wiley-Liss, Inc. [source] Simplified synthesis of 1,1,[14C]-methylene-di (2-naphthol).JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2004A radiochemical, kinetic approach Abstract The synthesis of the 1,1,[14C]-methylene-di-(2-naphthol) 2, as the radiolabeled probe of a possible interaction between the , -amyloid fibrils and the di-naphthol mojety in the Alzheimer's disease, is reported. Very simple radiochemical procedure, starting from [14C]paraformaldehyde, produced 8.66 MBq of compound 2 at the specific radioactivity of 1.22 TBq/mol. A mechanistic and kinetic approach allowed the comprehension of the right experimental conditions. The stability of compound 2 in acetonitrile solution was investigated, denoting a significative decomposition process through the transient formation of the 1,2-naphthyne intermediate. Copyright © 2004 John Wiley & Sons, Ltd. [source] Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregatesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2009Rui Yang Abstract Chitosan-modified paclitaxel-loaded poly lactic- co -glycolic acid (PLGA) nanoparticles with a mean diameter of 200,300 nm in distilled water were prepared by a solvent evaporation method. The mean diameter increased dramatically in contact with the mouse (CDF1) plasma, as a function of chitosan concentration in the modification solution (e.g., 2670.5 nm for 0.7% chitosan-modified nanoparticles, NP3), but reverted to almost its original size (i.e., 350.7 nm for NP3) following 5 min of gentle agitation. The zeta potential of PLGA nanoparticles was changed to positive by the chitosan modification. The in vitro uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell line (A549) were significantly increased by the modification. Most importantly, a lung-specific increase in the distribution index of paclitaxel (i.e., AUClung/AUCplasma) was observed for chitosan-modified nanoparticles (e.g., 99.9 for NP3 vs. 5.4 for TaxolÔ) when nanoparticles were administered to lung-metastasized mice via the tail vein at a paclitaxel dose of 10 mg/kg. Transient formation of aggregates in the blood stream followed by enhanced trapping in the lung capillaries, and electrical interaction-mediated enhanced uptake across the endothelial cells of the lung tumor capillary appear to be responsible for the lung-tumor-specific distribution of the chitosan modified nanoparticles. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:970,984, 2009 [source] The influence of aggregate microenvironment on the dissolution of oxazepam in ternary surfactant interactive mixturesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2002Peter J. Stewart ABSTRACT The purpose of this research was to test the hypothesis that the dissolution rate of oxazepam in interactive mixtures was dependent on the influence of surfactant within the microenvironment of mixed oxazepam-surfactant aggegrates produced during dissolution. The studies utilised both powder and intrinsic dissolution methodology; spectrophotometric assays were developed and validated and dissolution data were modelled using multi-exponential equations and dissolution rate constants estimated using non-linear least squares algorithms. For a series of water-soluble ternary additives to the oxazepam interactive mixture, sodium lauryl sulfate and cetrimide were shown not only to decrease aggregation through enhanced dispersion, but also to increase the dissolution rate constant. Such an increase in dissolution rate constant was observed in the intrinsic dissolution studies when surfactant concentrations exceeded the critical micelle concentration and the oxazepam solubility increased. Laser diffraction particle sizing during the dissolution process confirmed the presence of dispersed particles and aggregates and demonstrated that the presence of surfactant improved the state of dispersion. The results of studies using different rotational speeds produced unexpected increases in aggregation and decreases in dissolution rate constants at about 150 rev min,1, consistent with the transient formation of loose aggregates containing dissolved surfactant. [source] Kinetic simulation studies on the transient formation of the oxo-iron(IV) porphyrin radical cation during the reaction of iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)-porphyrin with hydrogen peroxide in aqueous solutionLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 5 2003Tapan Kumar Saha Abstract High-valent oxo-iron(IV) species are commonly proposed as the key intermediates in the catalytic mechanisms of iron enzymes. Water-soluble iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)porphyrin (Fe(III)TMPyP) has been used as a model of heme-enzyme to catalyse the hydrogen peroxide (H2O2) oxidation of various organic compounds. However, the mechanism of the reaction of Fe(III)TMPyP with H2O2 has not been fully established. In this study, we have explored the kinetic simulation of the reaction of Fe(III)TMPyP with H2O2 and of the catalytic reactivity of FeTMPyP in the luminescent peroxidation of luminol. According to the mechanism that has been established in this work, Fe(III)TMPyP is oxidized by H2O2 to produce (TMPyP)·+Fe(IV)=O (k1 = 4.5 × 104/mol/L/s) as a precursor of TMPyPFe(IV)=O. The intermediate, (TMPyP)·+Fe(IV)=O, represented nearly 2% of Fe(III)TMPyP but it does not accumulate in suf,cient concentration to be detected because its decay rate is too fast. Kinetic simulations showed that the proposed scheme is capable of reproducing the observed time courses of FeTMPyP in various oxidation states and the decay pro,les of the luminol chemiluminescence. It also shows that (TMPyP)·+Fe(IV)=O is 100 times more reactive than TMPyPFe(IV)=O in most of the reactions. These two species are responsible for the initial sharp and the sustained luminol emissions, respectively. Copyright © 2003 John Wiley & Sons, Ltd. [source] The mechanisms used by enteropathogenic Escherichia coli to control filopodia dynamicsCELLULAR MICROBIOLOGY, Issue 2 2009Cedric N. Berger Summary Enteropathogenic Escherichia coli (EPEC) subverts actin dynamics in eukaryotic cells by injecting effector proteins via a type III secretion system. First, WxxxE effector Map triggers transient formation of filopodia. Then, following recovery from the filopodial signals, EPEC triggers robust actin polymerization via a signalling complex comprising Tir and the adaptor proteins Nck. In this paper we show that Map triggers filopodia formation by activating Cdc42; expression of dominant-negative Cdc42 or knock-down of Cdc42 by siRNA impaired filopodia formation. In addition, Map binds PDZ1 of NHERF1. We show that Map,NHERF1 interaction is needed for filopodia stabilization in a process involving ezrin and the RhoA/ROCK cascade; expression of dominant-negative ezrin and RhoA or siRNA knock-down of RhoA lead to rapid elimination of filopodia. Moreover, we show that formation of the Tir-Nck signalling complex leads to filopodia withdrawal. Recovery from the filopodial signals requires phosphorylation of a Tir tyrosine (Y474) residue and actin polymerization pathway as both infection of cells with EPEC expressing TirY474S or infection of Nck knockout cells with wild-type EPEC resulted in persistence of filopodia. These results show that EPEC effectors modulate actin dynamics by temporal subverting the Rho GTPases and other actin polymerization pathways for the benefit of the adherent pathogen. [source] Photoinduced Energy- and Electron-Transfer Processes in Dinuclear RuII,OsII, RuII,OsIII, and RuIII,OsII Trisbipyridine Complexes Containing a Shape-Persistent Macrocyclic SpacerCHEMPHYSCHEM, Issue 1 2006Margherita Venturi Prof. Abstract The PF6,salt of the dinuclear [(bpy)2Ru(1)Os(bpy)2]4+complex, where 1 is a phenylacetylene macrocycle which incorporates two 2,2,-bipyridine (bpy) chelating units in opposite sites of its shape-persistent structure, was prepared. In acetonitrile solution, the Ru- and Os-based units display their characteristic absorption spectra and electrochemical properties as in the parent homodinuclear compounds. The luminescence spectrum, however, shows that the emission band of the RuIIunit is almost completely quenched with concomitant sensitization of the emission of the OsIIunit. Electronic energy transfer from the RuIIto the OsIIunit takes place by two distinct processes (ken=2.0×108and 2.2×107s,1at 298 K). Oxidation of the OsIIunit of [(bpy)2Ru(1)Os (bpy)2]4+by CeIVor nitric acid leads quantitatively to the [(bpy)2RuII(1)OsIII(bpy)2]5+complex which exhibits a bpy-to-OsIIIcharge-transfer band at 720 nm (,max=250,M,1cm,1). Light excitation of the RuIIunit of [(bpy)2RuII(1)OsIII(bpy)2]5+is followed by electron transfer from the RuIIto the OsIIIunit (kel,f=1.6×108and 2.7×107s,1), resulting in the transient formation of the [(bpy)2RuIII(1)OsII(bpy)2]5+complex. The latter species relaxes to the [(bpy)2RuII(1)OsIII(bpy)2]5+one by back electron transfer (kel,b=9.1×107and 1.2×107s,1). The biexponential decays of the [(bpy)2*RuII(1)OsII(bpy)2]4+, [(bpy)2*RuII(1)OsIII(bpy)2]5+, and [(bpy)2RuIII(1)OsII(bpy)2]5+species are related to the presence of two conformers, as expected because of the steric hindrance between hydrogen atoms of the pyridine and phenyl rings. Comparison of the results obtained with those previously reported for other Ru,Os polypyridine complexes shows that the macrocyclic ligand 1 is a relatively poor conducting bridge. [source] | |||||||||||||