1. The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzymeinhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine...Full Text Available
Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzymeinhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it...Full Text Available
Flavone and isoflavone phytoestrogens are plant chemicals and are known to be competitive inhibitors of cytochrome P450 aromatase with respect to the androgen substrate. Aromatase is the enzyme that...Full Text Available
Moenomycin A (MmA) belongs to a family of natural products that inhibit peptidoglycan biosynthesis by binding to the peptidoglycan glycosyltransferases (PGTs), the enzymes that make the glycan...Full Text Available
Finasteride, a specific and competitive inhibitor of 5α-reductase enzyme Type 2, inhibits the conversion of testosterone to dihydrotestosterone (DHT). In adults, DHT acts as primary androgen...Full Text Available
Leupeptin, a tripeptide inhibitor of some proteinases, was shown previously to maintain the stability of several enzymes (isocitrate lyase, fumarase, and catalase) in crude extracts of castor bean endosperm....Full Text Available
Oligopeptidic drugs such as β-lactams and angiotensin-converting enzymeinhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model...Full Text Available
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2prime sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Ab40 in transgenic mice with a single subcutaneous dose.
S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used ...
Green crab (Scylla serrata) alkaline phosphatase (EC 3.1.3.1) is a metalloenzyme, which catalyzes the nonspecific hydrolysis of phosphate monoesters. The kinetics of inhibition of the enzyme by sodium (2, 2'-bipyridine) oxodiperoxovanadate, pV(bipy), has been studied. The time course of the hydrolysis of p-nitrophenyl-phosphate catalyzed by the enzyme in the presence of different pV(bipy) concentrations showed that at each pV(bipy) concentration, the rate decreased with increasing time until a straight line was approached, the straight line slopes are the same for all concentrations. The results suggest that the inhibition of the enzyme by pV(bipy) is a slow, reversible reaction with fractional remaining activity. The microscopic rate constants are determined for the reaction of inhibitor with the enzyme. PMID:10691182
We quantified the resistance levels of transgenic rice plants, expressing Myxococcus xanthus protoporphyrinogen oxidase (PROTOX) in chloroplasts and mitochondria, to PROTOX inhibitors, acifluorfen, oxyfluorfen, carfentrazone-ethyl, and oxadiazon. We also determined whether active oxygen species-scavenging enzymes are involved in the resistance mechanism of transgenic rice. The transgenic rice line M4 was about >200-fold more resistant to oxyfluorfen than the wild-type (WT). M4 was also resistant to acifluorfen, carfentrazone-ethyl, and oxadiazon, but did not show multiple resistance to imazapyr and paraquat, which have different target sites. Acifluorfen, oxyfluorfen, carfentrazone-ethyl, and oxadiazon reduced the chlorophyll content in leaves of WT, but had minimal or no effect on M4. The...
Chorismate mutase, a branch-point enzyme in the aromatic amino acid pathway of Saccharomyces cerevisiae, and also a mutant chorismate mutase with a single amino acid substitution in the C-terminal part of the protein have been purified approximately 20-fold and 64-fold from overproducing strains, respectively. The wild-type enzyme is activated by tryptophan and subject to feedback inhibition by tyrosine, whereas the mutant enzyme does not respond to activation by tryptophan nor inhibition by tyrosine. Both enzymes are dimers consisting of two identical subunits of M_r 30,000, each one capable of binding one substrate and one activator molecule. Each subunit of the wild-type enzyme also binds one inhibitor molecule, whereas the mutant enzyme lost this ability. The enzyme reaction was observed by "1H NMR and shows a direct ...
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Trihydroxynaphthalene reductase catalyzes two intermediate steps in the fungal melanin biosynthetic pathway. The enzyme, a typical short-chain dehydrogenase, is the biochemical target of three commercial fungicides. The fungicides bind preferentially to the NADPH form of the enzyme. Three X-ray structures of the Magnaporthe grisea enzyme complexed with NADPH and two commercial and one experimental fungicide were determined at 1.7 {angstrom} (pyroquilon), 2.0 {angstrom} (2,3-dihydro-4-nitro-1H-inden-1-one, 1), and 2.1 {angstrom} (phthalide) resolutions. The chemically distinct inhibitors occupy similar space within the enzyme's active site. The three inhibitors share hydrogen bonds with the side chain hydroxyls of Ser-164 and Tyr-178 via a carbonyl oxygen (pyroquilon and 1) or via a carbonyl oxygen and a ring oxygen (phthalide). Active site residues ...
The syntheses of N-alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol derivatives having either a D- or an L-erythritol-3-sulfate functionalized N-substituent are reported. The alkylating agent used was a cyclic sulfate derivative, whereby selective attack of the nitrogen atom at the least hindered primary center afforded the desired ammonium salt. In aqueous solution, these salts were configurationally labile at the ammonium center. Sulfonium and/or selenonium analogues of the ammonium salts were prepared by analogous reactions. The chalcogen salts were obtained as mixtures of diastereomers, separable in some cases, differing only in the stereochemistry at the configurationally stable sulfur or selenium atoms. Proof of configuration and conformation of each compound was obtained by detailed NMR experiments. The compounds are six-membered ring analogues of salacinol, a known sulfonium-salt glucosidase inhibitor. Evaluation of the target compounds for ...
1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 ...
The photoaffinity probes [#gamma#-"3"2P]2-azidoATP (2-N_3ATP) and [#alpha#-"3"2P]8-azido-ATP (8-N_3ATP) were used to investigate the binding of ATP to highly purified 2-5A synthetase. 2-N_3APT and 8-N_3ATP are substrates for 2-5A synthetase. In this study the authors show that 2- and 8-N_3ATP are competitive inhibitors of the enzymatic conversion of ATP to 2-5A. Ultraviolet irradiation results in the photoinsertion of 2-N_3ATP and 8-N_3ATP into the enzyme. The covalent photoinsertion of [#alpha#-"3"2P]8-N_3ATP into the 2-5A synthetase is proportional to the inactivation of the enzyme as UV irradiation is increased. Photolabeling of 2-5A synthetase is saturated at 1.5 mM 2-N_3ATP and 2.0 mM 8-N_3ATP. Computer analysis of the curvilinear Scatchard plots of the 2-5A synthetase suggest the presence of high-affinity and low-affinity binding sites that may correspond to the acceptor and the 2'-adenylation sites of the ...
The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP_3-mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKC#alpha#) was specified using isotype-specific pseudosubstrate, which showed pronounce ...
Abstract:- Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn-s disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn-s disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and t...
Ethylene is a plant hormone that elicits a wide variety of responses in plant tissue. Among these responses are the hastening of abscission, ripening and senescence. In 1979 it was discovered that 1-amino-1-cyclopropane carboxylic acid is the immediate biosynthetic precursor to ethylene. Given the obvious economic significance of ethylene production the authors concentrated their studies on the conversion of ACC to ethylene. They delved into mechanistic aspects of ACC oxidation and they studied potential inhibitors of ethylene forming enzyme (EFE). They synthesized various analogs of ACC and found that EFE shows good stereodiscrimination among alkyl substituted ACC analogs with the 1R, 2S stereoisomer being processed nine times faster than the 1S, 2R isomer in the MeACC series. They also synthesized 2-cyclopropyl ACC which is a good competitive inhibitor of EFE. This compound also causes time dependent loss of EFE activity ...
... Corrosion Inhibitors Equipment on Environmental Expert Find and compare a variety of corrosion inhibitors equipment on the world's largest environmental industry portal. View ...
This chapter will review the literature on cobalamin- and corrinoid-containing enzymes. These enzymes fall into two broad classes, those using methylcobalamin or related methylcorrinoids as...Full Text Available
The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, the authors examined the effects of intravenous infusion of angiotensin II on the rate of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar1-leu8-angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornical organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II ...
In our previous work, we demonstrated that biomass-generated producer gas can be converted to ethanol and acetic acid using a microbial catalyst Clostridium carboxidivorans P7{sup T}. Results showed that the producer gas (1) induced cell dormancy, (2) inhibited H{sub 2} consumption, and (3) affected the acetic acid/ethanol product distribution. Results of this work showed that tars were the likely cause of cell dormancy and product redistribution and that the addition of a 0.025{mu}m filter in the gas cleanup negated the effects of tars. C. carboxidivorans P7{sup T} can adapt to the tars (i.e. grow) only after prolonged exposure. Nitric oxide, present in the producer gas at 150ppm, is an inhibitor of the hydrogenase enzyme involved in H{sub 2} consumption. We conclude that significant conditioning of the producer gas will be required for the successful coupling of biomass-generated producer gas with fermentation to produce ethanol and acetic ...
Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single prophylactic treatment to ...
A decrease of inhibitor concentration in a medium is always desirable even if the inhibitor is not toxic. In this connection, a sharp increase in the protective effect of certain corrosion inhibitors when cathodic polarization was applied to the metal is reviewed. The importance of a simultaneous account of the chemical structure of inhibitor and the nature of the metal corrosion under cathodic polarization is outlined. Some examples of applying this combined protection of metals are discussed.
Background and purpose:Diphenyleneiodonium (DPI) is often used as an NADPH oxidase inhibitor, but is increasingly being found to have unrelated side effects. We investigated its...Full Text Available
Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children...Full Text Available
Chemical genetics is an emerging approach to investigate the biology of host-pathogen interactions. We screened several inhibitors of ATP-dependent DNA motors and detected the gyrase B inhibitor coumermycin...Full Text Available
The Production of Highly Active Human Blood Plasma Butyrylcholinesterase Preparation by Gene Engineering Methods to Create Protective Means against Poisoning by Organophosphorous Cholinesterase Inhibitors
The biomedical and ecological interest for the microwave impact on the Earth biosphere is continuously increased since the industrial, military and communication activities strongly contribute to the electromagnetic stress of living bodies. In the next the authors present some of the main results obtained regarding the microwave exposure of various types of biological material: bacteria, fungi, young plant seedlings, dry seeds, animal tissues. The electromagnetic exposure was carried out in open space in well controlled environmental conditions by using 10.75 GHz/1 m W cm{sup -2} microwaves. Biochemical assays and cytogenetic tests have been carried out to reveal the changes induced post irradiation. The response of some pathogen bacteria, have been emphasized by means of turbidimetric measurements - the stimulatory effect being noticed at the level of the microbial population density (the stimulation of the human body microbial flora seems to be one of the side effects of microwave ...
The display of proteins such as feed enzymes at the surface of bacterial spore systems has a great potential use for animal feed. Feed enzymes increase the digestibility of nutrients, leading to greater...Full Text Available
A high-throughput assay for enzyme activity has been developed that is reaction independent. In this assay, a small-molecule yeast three-hybrid system is used to link enzyme catalysis to transcription...Full Text Available
Four-enzyme section of the shikimate pathway (Aro B, D, E, and K) of Streptococcus pneumoniae has been studied. Kinetic properties of the individual enzymes and three- and four-enzyme linked reactions have been characterized in vitro. On the basis of the data measured in spectrophotometric and LC-MS experiments, kinetic mechanisms of the enzymes have been suggested and all kinetic parameters have been identified. Kinetic models for these three- and four-enzyme sections of the shikimate pathway have been constructed and validated. The model of the four-enzyme section of shikimate pathway has been employed to design an inhibition-sensitive reconstituted pathway for a high-throughput screening effort on the shikimate pathway. It was demonstrated that using the model it was possible to optimize this reconstituted pathway in such a way to provide equal sensitivity of ...
Protein isolated from hen egg-white and functions as a bacteriostatic enzyme by degrading bacterial cell walls. First enzyme ever characterized by protein ...
The acid corrosion inhibition process of mild steel in 1M HCl by 1-butyl-3-methylimidazolium chlorides (BMIC) and 1-butyl-3-methylimidazolium hydrogen sulfate ([BMIM]HSO4) has been investigated using electrochemical impedance, potentiodynamic polarization and weight loss measurements. Potentiodynamic polarization studies indicate the studied inhibitors are mixed type inhibitors. For both inhibitors, the inhibition efficiency increased with increase in the concentration of the inhibitor and the effectiveness of the two inhibitors are in the order [BMIM]HSO4>BMIC. The adsorption of the inhibitors on mild steel surface obeyed the Langmuirs adsorption isotherm. The effect of temperature on the corrosion behavior in the presence of 5x10-3M of inhibitors was studied in the temperature range of 3...
A proposed inhibitor for steel corrosion in hydrochloric acid consists essentially of 0.5% of an inhibitor called BA-6, 0.25-0.5% of 1-hexynol-3, and about 0.02% of potassium iodide (calculated on the amount of acid). The inhibitor DA-6 is produced by condensing benzylamine with utrotropine. 1-Hexynol-3, secondary alcohol, is obtained from butyraldehyde and acetylene in the presence of caustic potash. The increase of potassium iodide concentration from 0.02-0.1% increases the protective action of the inhibitor. Hexynol, dipropargyl ester, and potassium iodide must be introduced in HC1 before injection of the latter into the well.
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes. Mammalian IDO expression is induced by cytokines and has antimicrobial and immunomodulatory effects. A major role of mammalian TDO is to supply nicotinamide adenine dinucleotide (NAD(+)). In fungi, the IDO homologue is thought to be expressed constitutively and supply NAD(+), as TDO is absent from their genomes. Here, we reveal the distribution of IDO genes among fungal species and characterize their enzymatic activity. The yeast, Saccharomyces cerevisiae has only one IDO gene, whereas the koji-mold, Aspergillus oryzae has two genes, IDO? and IDO?. The A. oryzae IDO? showed more similar enzymatic properties to those of S. cerevisiae IDO than IDO?, suggesting that the A. oryzae IDO? is a functional homologue of the S. cerevisiae IDO. From the IDO? gene, two isoforms, IDO? and IDO?(+) could be generated by alternative splicing. The latter contained a 17 amino ...
The enzyme indol-3-ylacetylglucose synthase (UDP-glucose:indol-3-ylacetate beta-D-glucosyltransferase) catalyses the reaction: [formula: see text] This is the first step in the series of reactions leading...Full Text Available
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify gene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
ObjectiveThe objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors...Full Text Available
The canonical Wnt/β-catenin pathway plays a pivotal role in regulating embryogenesis and tumorigenesis by promoting cell proliferation. BAMBI (BMP and activin membrane-bound inhibitor) has...Full Text Available
Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore...Full Text Available
Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease...Full Text Available
AimsTo assess the tolerability and pharmacokinetic profile of single and repeat doses of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers.Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
BackgroundSerine proteinase inhibitors (Serpins) are a large superfamily of structurally related, but functionally diverse proteins that control essential proteolytic pathways in...Full Text Available
Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of mortality. Infusion with proton pump inhibitors (PPIs) prevents recurrent bleeding after successful...Full Text Available
AimsTo describe the pharmacokinetic–pharmacodynamic (PK–PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation...Full Text Available
4-methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on...Full Text Available
Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70. Treatment with PDE-5 inhibitors is effective in the majority of men with ED. However, PDE-5 inhibitors are not effective...Full Text Available
The inhibitor action of unbranched polyamines on corrosion of low-carbon steel in 0.5 M sulfuric acid is studied through potentiostatic polarization curves. It is shown that the inhibitor efficiency I depends on the polyamine concentration and molecular structure. The quantum-mechanical calculations of molecular properties are accomplished through the MNDO method. Correlation between the measured I and physicochemical properties of the polyamine inhibitors in protonized and nonprotonized form is found with application of the general perturbation theory
Qualifying corrosion inhibitors for use in high velocity multiphase flowlines in arctic or subsea environments is discussed. The tests include high velocity flow loop corrosion tests, pumpability through 0.125 (0.318 cm) inch capillary at low temperatures, compatibility with Nylon 11, emulsion tendency testing, and partitioning characteristics. Laboratory and field data show the importance for using the above criteria for inhibitor selection.
The serpin ZPI is a protein Z (PZ)-dependent specific inhibitor of membrane-associated factor Xa (fXa) despite having an unfavorable P1 Tyr. PZ accelerates the inhibition reaction ∼2000-fold...Full Text Available
For an enzyme functioning predominantly in a seemingly housekeeping role of 5′ tRNA maturation, RNase P displays a remarkable diversity in subunit make-up across the three domains of...Full Text Available
The stability of catalase, fumarase, and isocitrate lyase from deliberately broken organelles in crude extracts from endosperm tissue of castor bean seedlings has been examined. These enzymes are relatively...Full Text Available
Phosphoglycerate kinase (PGK) from the hyperthermophilic bacterium Thermotoga maritima has been purified to homogeneity. A second larger enzyme with PGK activity and identical N-terminal sequence was...Full Text Available
A procedure is described for the purification of the enzyme indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (IAA-myo-inositol synthase). This enzyme...Full Text Available
In order to efficiently utilize natural cellulose materials to produce ethylene, three expression vectors containing the ethylene-forming enzyme (efe) gene from Pseudomonas...Full Text Available
OBJECTIVE: To evaluate the commercial microparticle enzyme immunoassay (MEIA), Abbott IMx Select Chlamydia, for the detection of Chlamydia trachomatis in women and to compare its performance with endocervical...Full Text Available
The recombinant product (rK39) of the 39-amino-acid repeats encoded by a kinesin-like protein-encoding gene of Leishmania chagasi was evaluated by enzyme-linked immunosorbent assay...Full Text Available
Endocervical swabs from 212 women and urethral swabs from 100 men were tested by the routine methods for McCoy cell culture and simultaneously by a novel enzyme amplified immunoassay test to detect...Full Text Available
Investigations of enzymes involved in DNA metabolism have strongly benefited from the establishment of single molecule techniques. These experiments frequently require elaborate DNA substrates, which...Full Text Available
We modified an existing enzyme-linked immunosorbent assay (ELISA) to be able to use new spectrophotometers which can measure the rate of color development in microtiter wells. This new kinetic-based...Full Text Available
Designer cellulosomes are precision-engineered multienzyme complexes in which the molecular architecture and enzyme content are exquisitely controlled. This system was used to examine enzyme cooperation...Full Text Available
The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available
Several independent studies of bacterial degradation of nitrate ester explosives have demonstrated the involvement of flavin-dependent oxidoreductases related to the old yellow enzyme (OYE) of yeast....Full Text Available
The rate constants for both acylation and deacylation of beta-lactamase PC1 from Staphylococcus aureus and the RTEM beta-lactamase from Escherichia coli were determined by the acid-quench method [Martin...Full Text Available
The mechanism by which enzyme IIIglc of the bacterial phosphotransferase system regulates the activity of crystalline glycerol kinase from Escherichia coli has been studied, and the inhibitory effects...Full Text Available
Genetic test systems involving microorganisms and liver enzyme preparations may be insufficient to detect compounds that require breakdown by enzymes provided by the microbial flora of the intestinal...Full Text Available
A general procedure for stabilization of O2-labile enzymes exploiting "salting out" of oxygen from the microenvironment in the molecular layers immediately adjacent to charged surfaces of polyionic...Full Text Available
The acid corrosion inhibition process of mild steel in 1 M HCl by 1-butyl-3-methylimidazolium chlorides (BMIC) and 1-butyl-3-methylimidazolium hydrogen sulfate ([BMIM]HSO{sub 4}) has been investigated using electrochemical impedance, potentiodynamic polarization and weight loss measurements. Potentiodynamic polarization studies indicate the studied inhibitors are mixed type inhibitors. For both inhibitors, the inhibition efficiency increased with increase in the concentration of the inhibitor and the effectiveness of the two inhibitors are in the order [BMIM]HSO{sub 4} > BMIC. The adsorption of the inhibitors on mild steel surface obeyed the Langmuir's adsorption isotherm. The effect of temperature on the corrosion behavior in the presence of 5 x 10{sup -3} M of inhibitors was studied in the temperature range of 303-333 K. ...
The acid corrosion inhibition process of mild steel in 1 M HCl by 1-butyl-3-methylimidazolium chlorides (BMIC) and 1-butyl-3-methylimidazolium hydrogen sulfate ([BMIM]HSO_4) has been investigated using electrochemical impedance, potentiodynamic polarization and weight loss measurements. Potentiodynamic polarization studies indicate the studied inhibitors are mixed type inhibitors. For both inhibitors, the inhibition efficiency increased with increase in the concentration of the inhibitor and the effectiveness of the two inhibitors are in the order [BMIM]HSO_4 > BMIC. The adsorption of the inhibitors on mild steel surface obeyed the Langmuir's adsorption isotherm. The effect of temperature on the corrosion behavior in the presence of 5 x 10"-"3 M of inhibitors was studied in the temperature range of 303-333 K. The associated activation ...
Monitoring brine chemistry to determine the extent of potential adverse reactions was simplified by the development of a field brine test kit and a series of nomographs. Results of the kit analyses serve as input to the nomographs, which provide a graphic means of determining the scaling tendency (Saturation Index value) of a brine. Brines that do not tend to form scale may be corrosive. Saturation Index values have been correlated with various processes using data from geopressured wells in the Gulf Coast area. Control of scale in surface equipment of geopressured wells by chemical inhibitors has been successful. Downhole treatment with inhibitors to prevent scale formation in the production tubing is being investigated. Laboratory simulations indicate that an inhibitor squeeze treatment may be successful at the Gladys McCall No. 1 well. Inhibitor mixtures exhibit additive behavior at minimum ...
DescriptionEnzymes are natural catalysts that are used increasingly to replace environmentally harmful chemicals and to achieve better catalytic selectivity during pulp and paper processing. The main objective of this project is to identify novel plant enzymes for deeper understanding of the process of fibre formation and for future improvement of the quality parameters of wood fibres. Specific modification of the fibre characteristics will facilitate their use as raw materials for the current pulp and pap [continued...
The key factors of enzymatic lysis of cells are the interaction between the enzyme and the cell - catalytic and non-catalytic adsorption of enzyme on cell surface. Here, the studies of lysis of intact Escherichia coli cells by chicken egg white lysozyme were performed. It was found that the ionic strength has a dual effect onto the system. On the one hand, the desorption constant of the enzyme increases with the increase of the solution ionic strength, which results in a better enzyme performance. On the other hand, due to the higher osmosis, the cell lysis rate decreases with the increasing of ionic strength of the system. It was found that pH 8.6 and 30mM NaCl are optimal conditions for lysis of E. coli cells by lysozyme.
In this study, we investigated the kinetics of linoleic acid production via lipase-mediated hydrolysis of corn DDGS oil in a batch reactor with continuous mechanical agitation and developed a kinetic model that incorporated the product inhibition to study the complete hydrolysis. The model agreed very well with observed data; though situations with low enzyme dosage or low stirring rates were modeled successfully without product inhibition, actual product concentration in such situations was too low to exert any inhibitory effects. Increasing the enzyme concentration increased hydrolysis, and beyond certain enzyme concentrations, effects tended to fade away because of excessive enzyme desorption from the interface. An enzyme dosage within the range of 40-60KLU/L of oil dispersion could be ...
Abstract Flavin-containing reductases are involved in a wide variety of physiological reactions such as photosynthesis, nitric oxide synthesis, and detoxification of foreign compounds, including therapeutic drugs. Ferredoxin-NADP(H)-reductase (FNR) is the prototypical enzyme of this family. The fold of this protein is highly conserved and occurs as one domain of several multidomain enzymes such as the members of the diflavin reductase family. The enzymes of this family have emerged as fusion of a FNR and a flavodoxin. Although the active sites of these enzymes are very similar, different enzymes function in opposite directions, that is, some reduce oxidized nicotinamide adenine dinucleotide phosphate (NADP+) and some oxidize reduced nicotinamide adenine dinucleotide phosphate (NADPH). In t...
A new microbial transglutaminase (MTGase or MTG, EC 2.3.2.13) from a Streptomyces sp. strain isolated from Brazilian soil samples was characterized in crude and purified forms. The aim of this work is to provide relevant information about a new transglutaminase and to compare its characteristics with the well-known commercial transglutaminase from Ajinomoto Co. Inc. (Activa? TG-BP). The enzyme from Streptomyces sp., in both crude and pure forms, exhibited optimal activity in the 6.0?6.5 pH range and at 35?40?C. The results for the commercial enzyme were the same. A second maximum of activity was observed at pH?10.0 with both the crude Streptomyces sp. enzyme and the commercial enzyme. This interesting fact has not been reported in the literature previously. The fact that this second maximu...
We investigated the effect of pretreatment on the physicochemical characteristics-crystallinity, bed porosity, and volumetric specific surface of soybean hulls and production of cellulolytic enzymes in solid-state fermentation of Trichoderma reesei and Aspergillus oryzae cultures. Mild acid and alkali and steam pretreatments significantly increased crystallinity and bed porosity without significant change inholocellulosic composition of substrate. Crystalline and porous steam-pretreated soybean hulls inoculated with T. reesei culture had 4 filter paper units (FPU)/g-ds, 0.6?IU/g-ds ?-glucosidase, and 45?IU/g-ds endocellulase, whereas untreated hulls had 0.75?FPU/g-ds, 0.06?IU/g-ds ?-glucosidase, and 7.29?IU/g-ds endocellulase enzyme activities. In A. oryzae steam-pretreated soybean hulls had 47.10?IU/g-ds endocellulase compared to 30.82?IU/g-ds in untreated soybean hulls. Generalized linear statistical model fitted to ...
A heat storage compostion comprises sodium sulfate decahydrate as main component, a supercooling inhibitor, and a solid-liquid separation inhibitor. The composition is characterized in that hydraulic calcium sulfate and/or calcium sulfate dihydrate is contained as the solid-liquid separation inhibitor in an amount of 2-15 wt% base on the whole weight of the composition, whereby the solid-liquid separation, i.e. the sedimentation of the anhydrous sodium sulfate during the phase transition, is effectively prevented and the long-term stability is improved. The long-term stabilty of the composition can be more improved by addition of a silcia series of thickener.
The effect of sodium gluconate anion (SG) on the corrosion and scale inhibition of ordinary steel in simulated cooling water has been studied using weight loss, polarisation curves, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) techniques. SG was studied in concentration from 10{sup -4} M to 10{sup -1} M. Results obtained reveal that SG perform excellently as corrosion and scaling inhibitor for ordinary steel in simulated cooling water. An increase of SG concentration leads to the increase of the corrosion potential towards the positive direction. The inhibition efficiency was a low temperature dependence. The inhibitor mechanism was treated as an adsorption process according to Langmuir adsorption isotherm. The SEM/EDAX data show that was a corrosion and scale inhibitor.
Abstract Recently, a study of patients with rheumatoid arthritis who developed herpes zoster while taking a tumor necrosis factor (TNF)- inhibitor reported a decreased incidence of postherpetic neuralgia. The objective of this study was to investigate whether patients on TNF- inhibitors who developed herpes zoster have a lower incidence of subsequent development of postherpetic neuralgia. A retrospective review of herpes zoster patients on TNF- inhibitors (infliximab, etanercept, or adalimumab) was conducted in 12 dermatology clinics. Medical records of such patients were reviewed thoroughly to confirm herpes zoster and TNF- inhibitors and any subsequent development of postherpetic neuralgia (pain score -3 out of 10 after 90 days of shingles onset) was noted. A total of 206 cases were revi...
An organic inhibitor for acid corrosion inhibition is described. The inhibitor is a condensation product of a mixture of diethyl- and dibutyl-thiourea with hexamethylenetatramine. This condensation product is preferably made by reacting a mixture of diethyl- and dibutyl-thiourea, in a weight ratio of from 1:5 to 5:1, with 0.1 to 1 mole of hexamethylene tetramine per mole of the thiourea mixture, at temperatures of from 100 to 150 C. It is possible to modify this by using other organic thiourea derivatives containing organic radicals (aliphatic or aromatic) having up to 10 carbon atoms, for example, ditoluyl-thiourea, in addition to the mixture of diethyl- and dibutyl-thiourea, but the amount by weight of these other derivatives must not exceed 20% of the diethyl-dibutyl-thiourea mixture. The advantages of the inhibitor are observed mainly when it is used in hydrofluoric acid solutions. 6 claims.
A robust fusion of the agricultural, industrial biotechnology, and energy industries can create a new strategic national capability for energy independence and climate protection. In his State of the Union Address (Bush 2006), President George W. Bush outlined the Advanced Energy Initiative, which seeks to reduce our national dependence on imported oil by accelerating the development of domestic, renewable alternatives to gasoline and diesel fuels. The president has set a national goal of developing cleaner, cheaper, and more reliable alternative energy sources to substantially replace oil imports in the coming years. Fuels derived from cellulosic biomass - the fibrous, woody, and generally inedible portions of plant matter - offer one such alternative to conventional energy sources that can dramatically impact national economic growth, national energy security, and environmental goals. Cellulosic biomass is an attractive energy feedstock because it is an abundant, domestic, renewable ...
Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The DADPH-binding dinucleotide folds of the {beta}-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the DADP- and ...
Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...
BackgroundThe most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment...Full Text Available
Multiple myeloma is a highly radiosensitive skeletal malignancy, but bone-seeking radionuclides have not yet found their place in disease management. We previously reported that the proteasome inhibitor...Full Text Available
There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.
Bridged monobactam {beta}-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C {beta}-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.
BackgroundRecent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding...Full Text Available
AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A2 (TxA2) receptor and synthase inhibitor, in healthy human subjects after...Full Text Available
1. Ro 15-8081 (Hoffmann-La Roche, Basle, Switzerland) is a novel mixed 5-HT/noradrenaline uptake inhibitor producing potent antinociceptive effects in animal pain models. 2. In healthy man, two models...Full Text Available
Clavulanic acid, Z-(2R,5R)-3-(β-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3,2,0] heptane-2-carboxylic acid, has been shown to be an effective inhibitor of the β-lactamases of the...Full Text Available
BackgroundUpon CD95/Fas ligation, the initiator caspase-8 is known to activate effector caspases leading to apoptosis. In the presence of zVAD-fmk, a broad-spectrum caspase inhibitor,...Full Text Available
The lipid composition of skin is important to a variety of functions served by this organ. Therefore, skin expresses multiple enzymes that synthesize and metabolize lipids. An important class of lipid...Full Text Available
Telomere maintenance is essential for cellular immortality, and most cancer cells maintain their telomeres through the enzyme telomerase. Telomeres and telomerase represent promising anticancer...Full Text Available
Abstract Trametes hirsuta, a filamentous basidiomycete, was successfully cultivated in solid-state fermentation (SSF) on a mixture of pine wood chips and orange peel in a novel bioreactor that allows mixing of the inoculated solid material during the fermentation. Copper sulfate or xylidine (2,5-dimethylaniline) were added to enhance the production of enzymes, especially laccases. For comparison, Trametes hirsuta was also cultivated in submerged conditions. The effect of additives in SSF was low, whereas the choice of the solid material and the rotation of the reactor vessel showed a significant influence on the enzyme production. The space-time yields for the fermentations were calculated and showed that SSF on low-cost substrates can effectively produce extracellular enzymes at a suffici...
We describe the stabilization by pressure of enzymes, including a hydrogenase from Methanococcus jannaschii, an extremely thermophilic deep-sea methanogen. This is the first published...Full Text Available
Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with {sup 60}Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.
Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with "6"0Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.
All treatments for obesity, including dietary restriction of carbohydrates, have a goal of reducing the storage of fat in adipocytes. The chief enzyme responsible for the mobilization of FFA from adipose...Full Text Available
BackgroundEnzyme-linked immunosorbent assay (ELISA) is a standard immunoassay to estimate a protein's concentration in a sample. Deploying ELISA in a microarray format permits simultaneous...Full Text Available
Diagnostic accuracy of the currently available serum markers of cardiac injury, such as myoglobin, creatine kinase and its myocardial isoform, are altered in patients with renal failure. It is shown...Full Text Available
Carboxylesterases (CE) are ubiquitous enzymes that hydrolyze numerous ester-containing xenobiotics, including complex molecules, such as the anticancer drugs irinotecan (CPT-11) and capecitabine...Full Text Available
Monitoring brine chemistry to determine the extent of potential adverse reactions has been simplified by the development of a field-brine test kit and a series of nomographs. Results of the kit analyses serve as input to the nomographs, which provide a graphic means of determining the scaling tendency (Saturation Index value) of a brine. Brines that do not tend to form scale may be corrosive. Saturation Index values were correlated with various processes using data from geopressured wells in the Gulf Coast area. Control of scale in surface equipment with chemical inhibitors has been successful. Numerous laboratory simulations of inhibitor squeeze operations were completed using core material with calcite present and absent. The corresponding wells were squeezed with phosphorous-containing inhibitors, and the flowback of brine was monitored for phosphorous concentrations vs time. A new procedure to measure the concentration ...
Hepatitis C virus NS3-4A is a membrane-bound enzyme complex that exhibits serine protease, RNA helicase, and RNA-stimulated ATPase activities. This enzyme complex is essential for viral genome replication...Full Text Available
Synthesis of the azido substituted non-steroidal anti-inflammatory drug 2-(2,6-dichloroanilino)phenylacetic acid and isotope labeling of this compound have been performed and are described. Initial evaluation of the binding ability and photoreactivity indicates that this compound has potential for photoaffinity labeling as well as enzyme selectivity studies. (author).
The rates of synthesis of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis are controlled by a signal transduction pathway defined by at least four regulatory genes:...Full Text Available
An antibody capture enzyme immunoassay (EIA) was adapted for the detection of immunoglobulin M (IgM) antibody to Sindbis (SIN) virus. Sera from humans with a febrile illness characterized by rash and...Full Text Available
A new semi-empirical algorithm for the radial distribution of dose is compared with available data. The algorithm is used to calculate the inactivation cross section for dry enzymes and viruses using an extended target model of a 1-hit detector. Agreement with data is at about the 15% level, approximating the precision of the data itself. (author).
NADP:malic enzyme from corn (Zea mays L.) leaves was purified by conventional techniques to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis....Full Text Available
Insulin-degrading enzyme (IDE) degrades insulin and other peptides, including the Aβ peptide of Alzheimer’s disease. However, the mechanism by which IDE acts on its substrates...Full Text Available
Hepatocyte nuclear factor (HNF) 4α is a key transcription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...Full Text Available
The bifunctional rat liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC...Full Text Available
The first enzyme-catalyzed reaction leading from indole-3-acetic acid (IAA) to the myo-inositol esters of IAA is the synthesis of indole-3-acetyl-1-O-β-d-glucose...Full Text Available
An enzyme-linked immunosorbent assay was used to compare Brucella melitensis major outer membrane proteins (MOMP) and whole-cell heat-killed antigens (HK) in measuring antibrucella immunoglobulin G...Full Text Available
One of the first technical applications of gene technology is reported here. The DNA of E. coli cells was rearranged such that these cells produce large quantities of the enzyme ..cap alpha..-galactosidase. This enzyme is used to split the trisaccharide, raffinose, which is formed during the production of sugar from sugar beet. By this means sugar yields can be increased and the energy required for sugar crystallisation reduced.
32P-Postlabeling analysis and enzyme-linked immunosorbent assay (ELISA) have been used to detect DNA adducts in peripheral blood lymphocytes from primary aluminum production plant workers who were exposed...Full Text Available
Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent-antibody assay (IFA), and Western immunoblot were used to test serum samples from 128 dogs for the presence of antibody to Borrelia...Full Text Available
The design of the time-resolved x-ray diffraction experiments reported in this and an accompanying paper was based on direct measurements of enzyme phosphorylation using [gamma-32P]ATP that were employed...Full Text Available
Field and laboratory work sponsored by the Gas Research Institute (GRI) and the Department of Energy (DOE) have shown that calcium-carbonate scale formation in waters produced with natural gas and oil can be prevented by injection of phosphonate inhibitor into the formation, even if the formation is sandstone without calcite binding material. Inhibitor squeeze jobs have been carried out on DOE's geopressured-geothermal Gladys MaCall brine-gas well and GRI's co-production wells in the Hitchcock field. Following the inhibitor squeeze on Gladys McCall, the well produced over five million barrels of water at a rate of approximately 30,000 BPD without calcium-carbonate scaling. Before the inhibitor squeeze, the well could not be produced above 15,000 BPD without significant scale formation. In the GRI brine-gas co-production field tests, inhibitor squeezes have been ...
Four trypsin inhibitor homologs, the first known from Dendroaspis angusticeps venom, were characterized using a combination of gel filtration, cation exchange, reverse-phase liquid chromatography, Edman degradation and mass spectrometry. The four toxins comprise two 57 residue and two 59 residue isoforms. The long toxins possess a Lys-Gln N-terminal extension lacked by the short toxins. The only other structural difference is an Arg/His replacement at position 55. The long Arg55 variant is identical to trypsin inhibitor E from the venom of Dendroaspis polylepis. The name epsilon-dendrotoxin is suggested so as to follow the nomenclature of Benishin, C.G., Sorensen, R.G., Brown, W.E., Krueger, B.K., Blaustein, M.P., 1988. Four polypeptide components of green mamba venom selectively block certain potassium channels in rat brain synaptosomes. Mol. Pharmacol. 34, 152-159. Among snake venom protease inhibitors, the ...
We consider the role of quantum effects in the transfer of hyrogen-like species in enzyme-catalysed reactions. This study is stimulated by claims that the observed magnitude and temperature dependence of kinetic isotope effects imply that quantum tunneling below the energy barrier associated with the transition state significantly enhances the reaction rate in many enzymes. We use a path integral approach which provides a general framework to understand tunneling in a quantum system which interacts with an environment at non-zero temperature. Here the quantum system is the active site of the enzyme and the environment is the surrounding protein and water. Tunneling well below the barrier only occurs for temperatures less than a temperature $T_0$ which is determined by the curvature of potential energy surface near the top of the barrier. We argue that for most enzymes this temperature is less than room ...
Objectives- Investigate the potential for the use of enzymes to bring about improvements in the recycling of recovered waste paper sources~%~~%~- Optimise enzyme formulations and process conditions to maximise benefits. - Produce recovered fibre at lower energy and chemical costs than is currently achievable using 'classical' de-inking techniques.~%~~%~- Improve recycled fibre quality and~%~~%~- All of the above will allow a greater use of recovered paper resources, which would otherwise be diposed of by [continued...]DescriptionThe project proposes to carry out an initial literature review to update the consortium on the currently available publications relating to the use of enzymes in de-inking.. This will be followed by an intensive laboratory study in an upgraded facility which will allow enzyme formulations and mechanisms to be studied. This ...
The effect of sodium gluconate anion (SG) on the corrosion and scale inhibition of ordinary steel in simulated cooling water has been studied using weight loss, polarisation curves, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) techniques. SG was studied in concentration from 10-4M to 10-1M. Results obtained reveal that SG perform excellently as corrosion and scaling inhibitor for ordinary steel in simulated cooling water. An increase of SG concentration leads to the increase of the corrosion potential towards the positive direction. The inhibition efficiency was a low temperature dependence. The inhibitor mechanism was treated as an adsorption process according to Langmuir adsorption isotherm. The SEM/EDAX data show that was a corrosion and scale inhi...
Various chemical, physical, and mechanical methods to prevent unwanted deposition of mineral scale are described. The suitability of the different methods, which largely depends on the specific features and requirements of the system involved, is discussed. Special emphasis is placed upon the threshold treatment, where the growth process is retarded by the addition of trace amounts of growth inhibitors. Growth experiments have been performed on barium sulfate and calcium sulfate dihydrate seed crystals, suspended in a supersaturated solution with and without organic bisphosphonates as inhibitors. Two methods are selected for the analysis of the growth data. A degree of inhibition is defined to obtain a quantitative description of the influence of a growth inhibitor on the growth rate of the crystals. In addition the influence of the molecular structure of various bisphosphonates with different substituents is shown. The ...
Vanadium carbide is the most effective grain growth inhibitor for ultrafine WC-Co composites due to its high solubility and mobility in the cobalt phase at relatively low temperatures; however, there are still some debates over the best way to introduce it into the WC-Co formulation. In this paper, the differences between admixed and chemically doped grain growth inhibitors on the microstructural development and properties of an ultrafine WC-10Co composite are discussed. The densification rate of chemically doped samples is slower in the early stage of sintering and the WC grain sizes of the sintered alloys are finer than those of admixed samples, leading to the increase of hardness and transverse rupture strength of the sintered alloys. The effectiveness of the chemically doped inhibitor ...
To establish a relationship between the molecular structure of polycarboxylates and their growth-retarding influence on barium sulfate, seeded-suspension-growth experiments were performed at various inhibitor concentrations and pH values. Two types of polycarboxylates with a molecular structure based on their polyacrylic or maleic acid were studied. The molecular structure of these compounds were varied by particle substitution with monomers containing hydroxyl, amide, and sulfonic acid, as well as hydrophobic groups. Hydrophobic groups are detrimental to good inhibitor performance, whereas the introduction of OH, NH {sub 2}, or SO {sub 3} H groups presents opportunities to enhance the inhibitor effectiveness. The sequence in performance of the compounds on barium sulfate was compared with the sequence formerly obtained for calcium sulfate dihydrate.
A study of the ordinary mild steel/cooling water interface, with and without inhibitor, was carried out using electrochemical impedance spectroscopy (EIS). EIS spectra in uninhibited medium reveal that a layer of corrosion and scale products is formed naturally and evolves with the immersion time. Monosaccharides derivatives were used as corrosion inhibitors. Most of them exhibit good behaviour against corrosion of ordinary steel in simulated water systems. Their inhibiting efficiency increases with concentration rise and depends on molecular structure especially -OH groups' position on two adjacent carbons and their number. In addition, the effect of MoO4^2^- on the corrosion inhibition in the presence of the best inhibitor was also studied by EIS. The addition of MoO4^2^- enhanced the in...
Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...
We have previously observed that auxin can act as a repressor of the wound-inducible activation of a chimeric potato proteinase inhibitor II-CAT chimeric gene (pin2-CAT) in transgenic...Full Text Available
Transformed Drosophila Kc cell lines, resistant to methotrexate, an inhibitor of de novo purine and pyrimidine synthesis, have been obtained by calcium phosphate transfection of plasmids containing...Full Text Available
Background: Patients with a typical depression are more likely to respond to monoamine oxidase inhibitors than to tricyclic antidepressants. They are frequently offered psychotherapy...Full Text Available
Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available
BackgroundFinasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have...Full Text Available
Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy, an inherited human disorder with increased ventricular wall thickness, myocyte hypertrophy, and disarray. To understand...Full Text Available
PurposeDutasteride and finasteride are 5α-reductase inhibitors that dramatically decrease serum levels of dihydrotestosterone. Because androgens...Full Text Available
The treatment for erectile dysfunction (ED) was revolutionized with the development of phosphodiesterase type 5 (PDE5) inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis,...Full Text Available
We have synthesized a novel stable precursor, saligenin phosphorotrichloridate, which, on reaction with N-monobiotinyldiamines, generates a series of biotinylated covalent inhibitors of serine esterases....Full Text Available
BackgroundCelecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib...Full Text Available
BackgroundUnderstanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function...Full Text Available
Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently in vitro until it has adapted by mutation. Consequently, wild-type HCMV differ fundamentally from the passaged strains...Full Text Available
Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. The tuberous sclerosis complex (TSC) protein is a negative regulator of mTOR. In humans, loss of the...Full Text Available
Secreted human bronchial mucins, directly collected from macroscopically healthy bronchial mucosa, were prepared in the presence of six proteinase inhibitors, and analysed by electron microscopy. These...Full Text Available
BackgroundAurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently...Full Text Available
In the adult mammalian CNS, the growth inhibitors oligodendrocyte-myelin glycoprotein (OMgp) and the reticulon RTN4 (Nogo) are broadly expressed in oligodendrocytes and neurons. Nogo and OMgp...Full Text Available
Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary...Full Text Available
Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH). MMF has recently been shown to inhibit the enzymatic activity...Full Text Available
The present invention relates to a method of acidizing a subterranean formation or well bore employing an acidic solution containing a corrosion inhibitor composition comprising an inhibiting effective amount of an acetylenic alcohol, a quaternary ammonium compound, an aromatic hydrocarbon and an antimony compound.
Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients...Full Text Available
The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drug discovery against...Full Text Available
Auxin modulates diverse plant developmental pathways through direct transcriptional regulation and cooperative signaling with other plant hormones. Genetic and biochemical approaches have clarified...Full Text Available
Methylation of the arginine residues of histones by methyltransferases has important consequences for chromatin structure and gene regulation; however, the molecular mechanism(s) of methyltransferase...Full Text Available
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available
Protection from extinction of conditioned fear has been demonstrated when a conditioned inhibitor of fear is presented during extinction treatment. The present study assessed if similar results...Full Text Available
of a tethered dimer of HIV-1 proteinase complexed with an inhibitor. Bhat TN, Baldwin ET, Liu B, Cheng YS, Erickson JW. Nat Struct Biol. 1994 Aug;1(8):552-6. Abstract End...
AbstractPurposeThe aim of this study was to elucidate the effects of the Rho-kinase inhibitor, H-1152, on cultured human trabecular meshwork (HTM) cells, TM morphology,...Full Text Available
In this work, a new class of thiadiazole derivatives, namely 3,5-bis(2-thienyl)-1,3,4-thiadiazole (2-TTH) and 3,5-bis(3-thienyl)-1,3,4-thiadiazole (3-TTH), have been studied as possible corrosion inhibitors for mild steel in molar hydrochloric acid (1M HCl). Polarisation curves and AC impedance methods have been used. These studies have shown that the thiadiazole derivatives were very good inhibitors for mild steel in 1M HCl. Comparison of results showed that 3-TTH was the best inhibitor. The potential of zero charge (PZC) of mild steel was studied by ac impedance method, and the mechanism of adsorption has been predicted. X-ray photoelectron spectroscopy surface analysis with thiadiazole derivatives shows that it chemisorbed at the mild steel/HCl interface. The adsorption of these inhibitors followed Langmuir's adsorption isotherm. The electronic properties of 2-TTH and 3-TTH, obtained using ...
The notes describe in detail primary and secondary galvanic cells, fuel cells, electrochemical synthesis and electroplating processes, corrosion: measurments, inhibitors, cathodic and anodic protection, details of metal dissolution reactions, Pourbaix diagrams and purification of waste water from galvanic industries.
The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible...Full Text Available
Restenosis remains the main complication of balloon angioplasty and/or stent implantation. Preclinical testing of new pharmacologic agents preventing restenosis largely rely on porcine models, where...Full Text Available
The p21-activated kinases (PAKs), immediate downstream effectors of the small G-proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and...Full Text Available
Background & AimsData are conflicting on the benefit of selective serotonin reuptake inhibitors (SSRIs) for patients with irritable bowel syndrome (IBS);...Full Text Available
Terfestatin A (TrfA), terphenyl-β-glucoside, was isolated from Streptomyces sp. F40 in a forward screen for compounds that inhibit the expression of auxin-inducible...Full Text Available
Recently, CID755673 was reported to act as a highly selective inhibitor of protein kinase D (PKD). In the course of experiments using CID755673, we noticed that it exerted unexpected stimulatory...Full Text Available
Thaxtomin A is a phytotoxin produced by Streptomyces scabies and other Streptomyces species, the causative agents of common scab disease in potato and other taproot...Full Text Available
The cyclic AMP content of acini, freshly prepared from mammary tissue of lactating rats, was measured during incubation in vitro. Neither adrenergic agonists nor cyclic AMP phosphodiesterase inhibitors...Full Text Available
Selective phosphodiesterase type 5 inhibitors (PDE5Is) have revolutionized the treatment of erectile dysfunction (ED) in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in...Full Text Available
The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by ...
OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of...Full Text Available
PurposeTaxanes have effects on angiogenesis causing difficulties in separating biologic effects of chemotherapy from those due to angiogenesis inhibitors. This randomized...Full Text Available
Inhibition efficiency of some water-soluble hydrazones for C-steel corrosion in hydrochloric acid has been tested by weight loss, polarisation measurements and open circuit technique. The inhibition effect was attributed to the adsorption of the additives on the C-steel surface as supported by adsorption measurements at Pt electrode using cyclic voltammetry. Electrochemical measurements indicated that all the additives behave as cathodic-type inhibitors. The data obtained fit well to both the Temkin adsorption isotherm and the kinetic-thermodynamic model. The inhibition behaviour and its order were explained with the help of the proposed skeletal representation.
Nitrite is to be used to inhibit pitting corrosion during Extended Sludge Processing (ESP) at the Savannah River Plant. The required nitrite concentrations are expressed as a function of the slurries' nitrate ion concentration and temperature. In the most dilute slurries, the nitrite inhibitor requirement is independent of the nitrate ion concentration and depends only on the temperature of the waste. The nitrate-independent concentration ensures that there is sufficient inhibitor, in sludge slurries whose nitrate has been depleted by radiolysis, to prevent pitting corrosion induced by other corrosive anions (e.g., sulfate and chloride). The threshold nitrate concentration at which the nitrite level is expressed as a function only of temperature is 0.02 M.
Nitrite is to be used to inhibit pitting corrosion during Extended Sludge Processing (ESP) at the Savannah River Plant. The required nitrite concentrations are expressed as a function of the slurries` nitrate ion concentration and temperature. In the most dilute slurries, the nitrite inhibitor requirement is independent of the nitrate ion concentration and depends only on the temperature of the waste. The nitrate-independent concentration ensures that there is sufficient inhibitor, in sludge slurries whose nitrate has been depleted by radiolysis, to prevent pitting corrosion induced by other corrosive anions (e.g., sulfate and chloride). The threshold nitrate concentration at which the nitrite level is expressed as a function only of temperature is 0.02 M.
The objectives of the project were to develop operational techniques for promoting contaminant hideout return from tube support crevices and to identify the effect of chemical inhibitor application on corrodent transport. The implementation of routine procedures for promoting the return of sequestered corrodents could retard the progression of denting or other corrosion processes and improve steam generator availability. Tests also quantified the effect of inhibitor application on crevice hideout and hideout return processes, with the intention of developing a better understanding of the inhibition mechanism. By carefully monitoring the hideout and hideout return inventories, the program also has provided the opportunity to study steam generator concentration processes in general.
A chromium-free conversion coating for magnesium alloys were described. The conversion coating could be obtained when AZ31D magnesium alloy was immersed in a solution containing a manganese salt, phosphate and an inhibitor. Corrosion resistance of the chemical conversion coating was evaluated by anodizing polarization curve and salt immersion. XRD analysis showed that the conversion coating was mainly composed of Mn{sub 3}(PO{sub 4}){sub 2}. The morphology of the coating is observed by using SEM. The effect of electrolyte pH and concentration of inhibitor on coating growth are investigated. (orig.)
BackgroundXMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.ResultsWe extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy in vitro. Our data ...
Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. ...
Fixation of /sup 14/CO/sub 2/ and activities of sucrose-synthesizing enzymes, sucrose phosphate synthetase (SPS) and sucrose synthase (SS), were assayed in tissues of developing fruit and source leaves from Citrus paradisi Macf. SPS activity of both the outer, chlorophyllous layer of the fruit (flavedo) and source leaves was 10-fold greater than that of the inner, largely non-chlorophyllous layer of the fruit peel (albedo). In contrast, SS activity of the flavedo was 2-fold greater than that of the albedo and 10-fold greater than that of leaves. Fixation of /sup 14/C-photosynthates in isolated tissues (flavedo 2x > albedo) and their redistribution in intact fruit indicated that flavedo functions as both source and sink. Activities of sucrose-synthesizing enzymes were consistent with this dual function.
The aim of a joint effort by different research teams was to provide an improved procedure for enzyme activity profiling of field-sampled ectomycorrhizae, including recommendations on the best conditions and maximum duration for storage of ectomycorrhizal samples. A more simplified and efficient protocol compared to formerly published procedures was achieved by using manufactured 96-filter plates in combination with a vacuum manifold and by optimizing incubation times. Major improvements were achieved by performing the series of eight enzyme assays with a single series of root samples instead of two series, reducing the time needed for sample preparation, minimizing error-prone steps such as pipetting and morphotyping, and facilitating subsequent DNA analyses due to the reduced sequencing ...
White seabream (Diplodus sargus) is today recognized as a potential species for Mediterranean aquaculture. Still, scarce information exists on weaning practices in order to reduce the live food period. This study aims to evaluate the effect of an early weaning on fish larvae digestive enzymes activities. In order to accomplish this, larvae were weaned with an inert diet at 20days after hatching (DAH) (feeding regime W20) and a control group was weaned at 27DAH (feeding regime W27). Before weaning, the onset and development of the main digestive enzymes were studied. The pattern of variation of digestive enzymes activities were analyzed at 0, 2, 9, 13 and 20DAH, and from then on at 0, 1 and 3weeks after diet introduction; that is, at 20, 27 and 41days for feeding regime W20, and days 27, 34...
Tocopherols (vitamin E) are lipophilic antioxidants synthesized by all plants and are particularly abundant in seeds. Despite cloning of the complete suite of tocopherol biosynthetic enzymes and successful...Full Text Available
The astonishingly efficient location and excision of damaged DNA bases by DNA repair glycosylases is an especially intriguing problem in biology. One example is the enzyme uracil DNA glycosylase (UNG),...Full Text Available
This poster describes single-molecule tracking and total internal reflection fluorescence microscopy. It discusses whether the carbohydrate-binding module (CBM) moves on cellulose, how the CBM binds to cellulose, and the mechanism of cellulosome assembly.
Trypanosoma brucei contains two isoenzymes for glyceraldehyde-phosphate dehydrogenase (GAPDH); one enzyme resides in a microbody-like organelle, the glycosome, the other one is found in the cytosol....Full Text Available
This report describes a case of toxic myopathy in a two year old sheltie dog with clinical signs of profound weakness, myoglobinuria, and muscle enzyme elevations. The clinical signs were likely related...Full Text Available
BackgroundThe pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a...Full Text Available
1. Proteolytic enzyme activities were examined in the pancreas of zinc-deficient and control rats. 2. No change was detected in trypsin-plus-chymotrypsin activity. 3. Carboxypeptidase activity was...Full Text Available
1. An enzyme from Escherichia coli 9723 that reduces adenosine 3′-phosphate 5′-sulphatophosphate to inorganic sulphite is described. Extracts of E. coli...Full Text Available
BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available
We recently identified a cDNA encoding a putative isovaleryl-coenzyme A (CoA) dehydrogenase in Arabidopsis (AtIVD). In animals, this homotetrameric enzyme is located in mitochondria and catalyzes the...Full Text Available
The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes...Full Text Available
SYNOPSISRhomboid proteases are a fascinating class of enzymes that combine a serine protease active site within the core of an integral membrane protein. Despite having key roles...Full Text Available
The CCR4-NOT complex is the main enzyme catalyzing the deadenylation of mRNA. We have investigated the composition of this complex in Drosophila melanogaster by immunoprecipitation...Full Text Available
In germinating oil palm (Elaeis guineensis var D × P) seedling, an active lipase was present in the shoot but absent from both the kernel and the haustorium. It has an optimum...Full Text Available
SummarySoluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). Genetic variations...Full Text Available
Enzymes are versatile catalysts in laboratories and on an industrial scale; improving their immobilization would be beneficial to broadening their applicability and ensuring their (re)use. Lipid-coated...Full Text Available
Nitrate reductase from wheat (Triticum aestivum L. cv Bindawarra) leaves is inactivated by pretreatment with NADH, in the absence of nitrate, a 50% loss of activity occurring in 30...Full Text Available
Phospho-beta-galactosidase (P-beta-gal), the enzyme which catalyzes the first step in the metabolism of intracellular lactose phosphate, occurred at high specific activity in the cytoplasm in 12 of...Full Text Available
Since 2000, Escherichia coli producing CTX-M enzymes (especially CTX-M-15) have emerged worldwide as important causes of community-onset urinary tract and blood stream infections due...Full Text Available
URA5 genes encode orotidine-5′-monophosphate pyrophosphorylase (OMPpase), an enzyme involved in pyrimidine biosynthesis. We cloned the Histoplasma capsulatum URA5...Full Text Available
An enzyme active against carboxymethyl cellulose (CMC) was purified from the stationary-phase-culture supernatant of Clostridium josui grown in a medium containing ball-milled cellulose. The purification...Full Text Available
A Monascus pilosus strain was selected for production of intracellular α-galactosidase. Optimum conditions for mycelial growth and enzyme induction were determined. Galactose...Full Text Available
The speA gene in Bacillus subtilis encodes arginine decarboxylase, which catalyzes the conversion of arginine to agmatine. Arginine decarboxylase is an important enzyme...Full Text Available
Polyamine oxidase was purified to homogeneity from leaves of water hyacinth by the criterion of sodium dodecyl sulfate gel electrophoresis (SDS disc PAGE). The enzyme showed a high specificity for spermidine...Full Text Available
Several commonly occurring freshwater and marine plants and algae were screened for beta-D-galactosidase and beta-D-glucuronidase activities by using a 60-min enzyme assay based on the hydrolysis by...Full Text Available
Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and...Full Text Available
1. The proteolytic enzyme pronase, which degrades the endothelial cell glycocalyx, was perfused through single capillaries of frog mesentery. Hydraulic conductivity (Lp) of each vessel was determined...Full Text Available
Peripartal serum alkaline phosphatase activity and lactate dehydrogenase activity were measured in 30 dairy cows in order to examine the association between retained fetal membranes and enzyme activity....Full Text Available
Importance of the fieldThe cytochrome P450 (CYP) isoforms that are selectively induced following exposure to structurally-diverse chemicals often are the ones capable...Full Text Available
Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate...Full Text Available
Klebsiella oxytoca can use nitrate and nitrite as sole nitrogen sources. The enzymes required for nitrate and nitrite assimilation are encoded by the nasFEDCBA operon....Full Text Available
AIM:N-acetyltransferase 2 (NAT2) is an important enzyme catalyzing N-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate...Full Text Available
Microorganisms in the environment can often adapt to use xenobiotic chemicals as novel growth and energy substrates. Specialized enzyme systems and metabolic pathways for the degradation of man-made...Full Text Available
Two bacteriolytic enzymes secreted by Achromobacter lyticus M497-1 were purified and identified as being very similar (considering their amino acid composition and N-terminal sequence) to alpha- and...Full Text Available
CTX-M-25 is a novel extended-spectrum β-lactamase isolated from a single Canadian Escherichia coli isolate. Susceptibility testing demonstrated that this enzyme confers resistance...Full Text Available
Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur,...Full Text Available
As part of the study of cytokinin metabolic pathways, an enzyme, adenosine phosphorylase (EC 2.4.2.-), which catalyzed the ribosylation of N6-(Δ2-isopentenyl)adenine,...Full Text Available
BackgroundLead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1...Full Text Available
As with mammalian enzymes, green crab (Scylla serrata) alkaline phosphatase can be activated by Mg2+ through a time-dependent course. The activation is mainly a Vmax effect. Tsou's method was used to study the kinetic course of activation. The results show that the enzyme was activated by a complexing scheme that had not been previously identified: the enzyme first reversibly and quickly binds Mg2+ and then undergoes a slow reversible course to activation, with a relatively high activation energy (78 +/- 4 kJ/mol) and a slow conformational change. The activation reaction is a single molecule reaction, and the apparent activation rate constant is independent of Mg2+ concentration if the concentration is sufficiently high. The microscopic rate constants of activation and the association constant were determined from the measurements. The proposed scheme may also be applied to the Mg2+ activation mechanism for mammalian ...
Ion filtration chromatography on diethylaminoethyl-Sephadex A-25 has been used to separate two isozymes each of triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, glycerate 3-phosphate...Full Text Available
All molybdenum enzymes except nitrogenase contain a common molybdenum cofactor, whose organic moiety is a novel pterin called molybdopterin (MPT). To assist in elucidating the biosynthetic pathway of...Full Text Available
BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available
Tumor embolism occurs in 30 to 50% of all cases of cardiac myxoma, but the causes are still uncertain. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix...Full Text Available
ObjectivesIn 2003, the Omani Ministry of Health Child Health Care Program initiated a national Birth Defects (BD) Register. This paper reviews the magnitude and risk factors of birth...Full Text Available
Telomerase, a ribonucleoprotein enzyme that maintains telomere length, is crucial for cellular immortalization and cancer progression. Telomerase activity is attributed primarily to the expression of...Full Text Available
The proprotein convertases (PCs) are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that...Full Text Available
Chrysomelid leaf beetles use chemical defenses to overcome predatory attack and microbial infestation. Larvae of Chrysomela lapponica that feed on willow sequester plant-derived salicin...Full Text Available
INTRODUCTION:Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensin‐converting enzyme. However, other mechanisms that...Full Text Available
SUMMARYA gene eam in Clostridium difficile encodes a protein that is homologous to lysine 2,3-aminomutase (LAM) in many other species but does...Full Text Available
Phenylalanine hydroxylase was purified from crude extracts of human livers which show enzyme activity by usine two different methods: (a) affinity chromatography and (b) immunoprecipitation with an...Full Text Available
Progress is reported in the following subject areas: (1) chemistry of the arogenate molecule; (2) plant enzymology at the organismal level; (3) isolation of regulatory mutants in tobacco; and (4) stability of the haploid state in Nicotiana sylvestris.
The formation of the nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase in Clostridium thermoaceticum is stimulated by the presence of molybdate and selenite...Full Text Available
It was found that neither the enzymes of the grapes nor those of wine yeast Saccharomyces ellipsoideus strain 223 attacked the higher polysaccharides present in corn syrups. The alcohol...Full Text Available
BackgroundCyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2...Full Text Available
Rotazyme II, which is a shorter version of Rotazyme (less than 3 h), was compared with electron microscopy and Rotazyme for sensitivity and specificity on 229 human stool specimens. Compared with electron...Full Text Available
SummaryThe evolutionary pressures that shaped the specificity and catalytic efficiency of enzymes can only be speculated. While directed evolution experiments show that new functions...Full Text Available
Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in...Full Text Available
Isolated cauliflower (Brassica oleracea) bud plastids, purified by isopycnic centrifugation in density gradients of Percoll, were found to be highly intact, to be practically devoid...Full Text Available
Trypanothione reductase (TryR) is a key enzyme involved in the oxidative stress management of the Trypanosoma and Leishmania parasites, which helps to maintain an intracellular reducing environment...Full Text Available
FXYD1 (phospholemman) is a member of an evolutionarily conserved family of membrane proteins that regulate the function of the Na,K-ATPase enzyme complex in specific tissues and specific physiological...Full Text Available
BackgroundTrichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes.MethodsTwenty...Full Text Available
Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin sensitivity and are protected from...Full Text Available
BackgroundDiurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling...Full Text Available
A Citrobacter amalonaticus and a Morganella morganii producing the CTX-M-1 extended-spectrum β-lactamase (ESBL) were isolated from an area where this enzyme...Full Text Available
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and...Full Text Available
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available
Reversible protein glutathionylation plays a key role in cellular regulation and cell signaling and protects protein thiols from hyperoxidation. Sulfiredoxin (Srx), an enzyme that catalyzes the reduction...Full Text Available
Enolase is a multifunctional enzyme that plays important roles in many biological and disease processes. α-Enolase from human liver (hENO1) was expressed as a soluble protein and purified by...Full Text Available
Malate synthase (EC 4.1.3.2), an enzyme unique to the glyoxylate cycle, was purified to homogeneity from cotyledons of 72-hours, darkgrown cotton (Gossypium hirsutum L.) seedlings....Full Text Available
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an evolutionarily conserved glycolytic enzyme, is constitutively expressed in most cell types yet is induced to high levels during the development of...Full Text Available
In Pseudomonas paucimobilis UT26, gamma-hexachlorocyclohexane (gamma-HCH) is converted by two steps of dehydrochlorination to a chemically unstable intermediate, 1,3,4,6-tetrachloro-1,4-cyclohexadiene...Full Text Available
Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available
BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib,...Full Text Available
Investigations of psychrotrophic microorganisms have been limited even though the dominant environment of the Earth is cold and enzymes with high activities at low temperatures could have commercial...Full Text Available
To determine the N-acetyl-B-D-glucosaminidase (NAGase) and B-glucuronidase (B-Gase) activities in mastitic milk, basic enzyme assay conditions, distribution of NAGase and B-Gase, comparison of their...Full Text Available
Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal...Full Text Available
In the growing chloronema cell suspension cultures of the moss Funaria hygrometrica Hedw., activities of several enzymes have been found to be cell-density-dependent. Cyclic nucleotide...Full Text Available
BackgroundAs the first pathway-specific enzyme in carotenoid biosynthesis, phytoene synthase (PSY) is a prime regulatory target. This includes a number of biotechnological approaches...Full Text Available
Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine...Full Text Available
A nationwide survey of extended-spectrum β-lactamase (ESBL) production among Enterobacteriaceae, carried out in 2003, showed that CTX-M-type enzymes have achieved a sizeable...Full Text Available
Tyrosinase or polyphenol oxidase (EC 1.14.18.1) is the key enzyme in melanin biosynthesis and in the enzymatic browning of fruits and vegetables. The role of tyrosinase in the secondary metabolism of...Full Text Available
Data from an epidemiological study in Ontario, involving 304 dairy herds, were used to identify associations between selected production indices and lipoarabinomannan antigen serological test results...Full Text Available
Introduction:Smoking behaviors, including heaviness of smoking and smoking cessation, are known to be under a degree of genetic influence. The enzyme catechol O-methyltransferase...Full Text Available
The free radical theory of ageing posits that accrual of oxidative damage underlies the increased cellular, tissue and organ dysfunction and failure associated with advanced age. In support of this...Full Text Available
Antibody avidity to hen egg white lysozyme (HEWL) was measured by thiocyanate ion elution enzyme-linked immunosorbent assay (ELISA) in swine lymphocyte antigen (SLA) defined miniature pigs. Serum antibody...Full Text Available
Human IgG specific for beta-endorphin was identified by enzyme-linked immunoabsorbent assay and isolated by affinity chromatography. From a sample of 27 subjects, three individuals with major depression...Full Text Available
Monoclonal antibodies were produced against gamma-irradiated amastigotes of Leishmania major. Five antibodies (T16 through T20) were selected which reacted in enzyme-linked immunoassays with the intracellular...Full Text Available
1. ATP sulphurylase from Saccharomyces cerevisiae was purified 140-fold by using heat treatment, DEAE-cellulose chromatography and Sepharose 6B gel filtration. 2. The enzyme was stable...Full Text Available
Leaves of terrestrial plants are aerobic organs, and are not usually considered to possess the enzymes necessary for biosynthesis of ethanol, a product of anaerobic fermentation. We examined the ability...Full Text Available
Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein...Full Text Available
The accumulation of α-1,4-polyglucans is an important strategy to cope with transient starvation conditions in the environment. In bacteria and plants, the synthesis of glycogen and starch occurs...Full Text Available
SummaryThe prevalence of paralogous enzymes implies that novel catalytic functions can evolve on preexisting protein scaffolds. The weak secondary activities of proteins, which...Full Text Available
A novel acidizing process is used to increase the permeability of carbonate rock cores in the laboratory and to remove drilling fluid damage from cores and wafers. Field results show the benefits of the technology as applied both to injector and producer wells.
A cDNA encoding a cytochrome P450 enzyme was isolated from a cDNA library of the corpora allata (CA) from reproductively active Diploptera punctata cockroaches. This P450 from the endocrine...Full Text Available
NAD(P)H:rubredoxin oxidoreductase (NROR) has been purified from the hyperthermophilic archaeon Pyrococcus furiosus. The enzyme is exceedingly active in catalyzing the NADPH-dependent...Full Text Available
The corrosion behavior of steel in water from certain oil fields with various organic inhibitors was studied by applying potentiodynamic technique at pH 5.9. The inhibitors which were used include 2-methylbenzimidazole (I), 2-mercaptobenzimidazole (II), 2-mercapto-5-methylbenzimidazole (III), and 2-mercaptothiazole (IV). The inhibiting efficiency of the different additives was evaluated from their anodic and cathodic polarization curves at different temperatures. A comparative study of curve fitting procedures using the kinetic thermodynamic model and those utilizing well-known adsorption isotherms was undertaken. Three types of isotherms were used, Langmuir, Frumkin and Flory-Huggins isotherm. The results show that the kinetic-thermodynamic model and Flory-Huggins isotherms are more suitable to fit the data for the four inhibitors, at all applied temperatures. From the values of binding constants, K, the order of ...
A nucleoside triphosphate binding site on calf thymus RNA polymerase II was identified by using photoaffinity analogues of adenosine 5'-triphosphate and guanosine 5'-triphosphate. Both radiolabeled 8-azidoadenosine 5'-triphosphate (8-N3ATP) and radiolabeled 8-azidoguanosine 5'-triphosphate (8-N3GTP) bound to a single polypeptide of this enzyme. This polypeptide has a molecular mass of 37 kilodaltons and an isoelectric point of 5.4. Ultraviolet (UV) irradiation was necessary for photolabeling to occur. In addition, no labeling occurred when the probe was prephotolyzed or when the enzyme was inactivated. Furthermore, photolabeling of the enzyme could be decreased by preincubation with natural substrates. To provide evidence that the radiolabeled polypeptide forms a part of the domain of the nucleoside triphosphate binding site, experiments were performed using unlabeled 8-N3ATP. Although ...
The objective of this work was to investigate the efficiency of imidazole and its derivatives 4-methylimidazone, 4-methyl-5-hydroxymethylimidazone, 1-phenyl-4-methylimidazone, and 1-(p-tolyl)-4-methylimidazole for corrosion inhibition of copper in 0.5 M hydrochloric acid. Corrosion inhibition was studied using potentiodynamic methods. These studies have shown that 1-(p-tolyl)-4-methylimidazole has the best inhibitory efficiency. Activation energies were obtained by measuring the temperature dependence of the corrosion current. The activation energies in the presence of the various inhibitors are low (3--5 kJ/mol), with the best inhibitor showing the highest value. The adsorptive behavior of the imidazole derivatives on the copper electrode surface follows a Freundlich-type isotherm. The standard free energies of adsorption are also low (14--16 kJ/mol), indicating that imidazole and its derivatives physisorb on the copper surface. Possible ...
The objective of this work was to investigate the efficiency of imidazole derivatives for corrosion inhibition of copper in 0.5 M hydrochloric acid. Corrosion inhibition was studied using impedance spectroscopy. Imidazole and its derivatives 4-methylimida-zole, 4-methyl-5-hydroxymethylimidazole, 1-phenyl-4-methylimidazole, 1-(p-tolyl)-4-methylimidazole were investigated. These studies have shown that 1-(p-tolyl)-4-methylimidazole is the best inhibitor in this series and that it acts as mixed inhibitor. The nature of the chemical interaction between these molecules and the copper surface was investigated by Cu exposed to solutions having two very different pH values: 0.5 M HCl and unbuffered purified water. X-ray photoelectron spectroscopy and secondary ion mass spectrometry were used to explore the nature of the interaction. Possible mechanisms of corrosion inhibition for these molecules are discussed.
Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. The authors have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5[prime] noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 559 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline [gamma]-polypeptide locus CRYGP1(p5G1). 31 refs., 3 figs., 3 tabs.
The methodology of the drip procedure of the Standard Test Method for Evaluating the Influence of Thermal Insulation on External Stress Corrosion Cracking Tendency of Austenitic Stainless Steel (ASTM C 692-95a) was used to research the effect of halogens and inhibitors on the external stress corrosion cracking (ESCC) of Type 304 stainless steel as it applies to the insulation industry. Simulated insulation extraction solutions were made with pure chemical reagents for the halogens and inhibitors. The results indicated that sodium silicate compounds that were higher in sodium were more effective for preventing chloride-induced ESCC in Type 304 austenitic stainless steel. Potassium silicate was not as effective as sodium silicate. Fluoride, bromide, and iodide may cause ESCC but they were much less active than chloride and could be effectively inhibited by sodium silicate compound. The addition of fluoride ions to the chloride/sodium silicate ...
Corrosion in drilling and well stimulation is described in relation to acid corrosion inhibition, acid inhibitors, acetylenic inhibitors, synergistic blends, metallurgy, wellbore tubulars, coiled tubing, and high alloy tubular materials. Acidizing is a procedure for stimulating oil and gas wells. Factors that have an important influence on the reaction rate and the way in which acid reacts with rock include temperature, acid concentration, acid volume, injection velocity, acid viscosity, and fluid loss properties of the formation. The cost of drill pipe failures are $1 per fot of hole drilled, which is a significant fraction of the drilling cost. Steps in a test procedure are listed, as well as factors which determine the extent of acid corrosion in a given situation including acid type and strength, metal type, temperature, contact time; pressure, and volume/surface area ratio. Underbalanced drilling is a method for completing oil and gas ...
Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...
Pulses are rich in nutrients. The existence of anti-nutritional components and the length of time required for preparation have, however, limited their frequency of use compared to recommended intake levels. Anti-nutritional components in pulses can be largely removed by heat treatment. Additionally pre-treatment of pulses with heat and processing of seeds into flour could further enhance their use by decreasing processing and preparation times. In this study, trypsin inhibitor activity, functional properties, and microstructural characteristics of flours prepared from different varieties of lentil, chickpea, and pea as affected by roasting and boiling were evaluated. Both thermal treatments resulted in significant reduction (p<0.05) in trypsin inhibitor activity ranging from -95.6% to -37...
The corrosion behavior of hard metals with VC and Cr3C2 grain growth inhibitors was investigated in alkaline solutions by electrochemical methods. The two inhibitors have opposite effects on the corrosion behavior: Cr3C2 significantly improves the corrosion behavior, whereas VC-containing alloys show a poor resistance. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and analytical transmission electron microscopy (TEM) analyses of the distributions of Cr and V in the composite material, as well as in the surface layers formed during corrosion were employed to clarify the influence of these elements on the corrosion behavior. The measurements showed that VC is precipitated mostly along the WC/binder interface after the liquid-phase sintering process, while Cr3C2 is almost homogene...
Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore and to analyze structure-activity relationships we synthesized a series of truncated derivatives and analogs of RB-2, including 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinones, 1-amino-2-methyl-4-arylaminoanthraquinones, 1-amino-4-bromoanthraquinone 2-sulfonic acid esters and sulfonamides, and bis-(1-amino-4-bromoanthraquinone) sulfonamides, and investigated them in preparations of rat NTPDase1, 2, and 3 using a capillary electrophoresis assay. Several 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinone derivatives inhibited E-NTPDases in a concentration-dependent manner. The 2-sulfonate group ...
To determine a rat strain appropriate for carcinogenicity testing of FYX-051, a xanthine oxidoreductase inhibitor, we performed a 4-week oral toxicity study by administering 0.3, 1 and 3?mg/kg, and 1, 3 and 10?mg/kg of FYX-051 to male Sprague-Dawley (SD) and Fischer (F344) rats, respectively. Histopathology revealed that the degree of FYX-051-induced nephropathy was 3-fold stronger in SD rats than in F344 rats. Our previous study demonstrated that the key factor of species differences in FYX-051-induced nephropathy is purine metabolism. This observation led us to examine the involvement of purine metabolism in differences among two strains of rats. However, purine metabolism was proven not to be implicated as an important factor. Subsequently, other factors responsible for the strain diffe...
Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC50 values of 1.0, 2.6, and 1.5 mM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.
A protective film has been developed on the surface of carbon steel in low chloride aqueous environment using a synergistic mixture of an environmentally friendly phosphonic acid, N,N-bis(phosphonomethyl) glycine (BPMG), and zinc ions. Impedance studies of the metal/solution interface indicated that the surface film is highly protective against the corrosion of carbon steel in the chosen environment. Potentiodynamic polarization studies showed that the inhibitor is a mixed inhibitor. X-ray photoelectron spectroscopic analysis (XPS) of the film showed the presence of the elements iron, phosphorus, nitrogen, oxygen, carbon, and zinc. Deconvolution spectra of these elements in the surface film showed the presence of oxides/hydroxides of iron(III), Zn(OH)2, and [Zn(II)-BPMG] complex. This infe...
The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drug targets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...
Penile rehabilitation therapy following radical prostatectomy is a much debated topic. Erectile dysfunction is still a significant contributor to postoperative morbidity following radical prostatectomy, despite meticulous nerve-sparing technique. Secondary smooth muscle changes in the penis have been identified as the underlying causes of penile atrophy, veno-occlusive dysfunction, and fibrosis. Initial observations that intracavernous injection therapies used on a regular basis postoperatively resulted in improvements in the return of spontaneous erectile function led to the development of penile rehabilitation protocols. Chronic dosing of PDE-V inhibitors is now commonly used by urologists after radical prostatectomy. Despite the current enthusiasm of penile rehabilitation therapy, current scientific evidence with clinical trials is still limited. PMID:19255627
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
Some N-containing or S-containing organic substances and some acetylenic alcohols were tested as inhibitors of the corrosive attack suffered by Fe-based metallic glasses in deaerated 0.1 N sulfuric acid (H{sub 2}SO{sub 4}) solution at 25 C. It was verified that the specific action these compounds exerted on the corrosion process of the amorphous alloys was similar to the one these compounds exerted on polycrystalline iron. The most efficient substances were those containing a sulfur atom with available lone pairs, which chiefly inhibited the anodic reaction of both metal specimens. Owing to the chemical and physical homogeneity of the amorphous alloy, the chemisorbed inhibitor film that formed on the glassy surface was more stable and protective than that formed on the polycrystalline iron.
Soybean is one of the most economical and nutritious food packed with basic nutrients that combat diseases stemming from mal- and under-nutrition. Despite its rich nutritional profile, use of soybean in food has been limited because soybean proteins are often associated with compounds, which could exert a negative impact on the nutritional quality of the protein. Trypsin inhibitor (TI) is one of the important anti-nutritional factors that exert negative effect by causing growth inhibition. Soybean cultivar VLS-2 was irradiated with 250 Gy gamma rays in a gamma cell (200) with 60Co source installed at BARC to induce mutations for low trypsin inhibitor content. Three mutants with lower levels of TI content were identified and can be utilized for developing elite varieties of soybean. (author)
...comAbstract: Hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, is a rapidly increasing type of cancer in recent years in the United States. Current treatment modalities to halt the disease progression are only marginally effective. The mainstay treatment ...In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, Sk-Hep-1. MMP-2 and MMP-9 activities were further modulated by cytokines, inducers and inhibitors, including NM. In ... Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression, such as proliferation, invasion and metastasis, and by inducing apoptosis. Last update: 2 September 2011 JavaScript seems ...
Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...
Summary Background:- Cholinesterase inhibitors form the mainstay of treatment for persons with mild-to-moderate Alzheimer-s disease (AD). The rivastigmine patch may increase compliance and the proportion of patients maintaining an efficacious dose compared with oral cholinesterase inhibitors. Objective:- To investigate the proportion of patients who reached and maintained the target rivastigmine patch dose compared with the target rivastigmine capsule dose reported in clinical trials. Methods:- This was a multicentre, 24-week, open-label study in persons with probable AD and a Mini-Mental State Examination (MMSE) score of --10 and --26. The primary outcome was the proportion of patients (ITT population) treated with 9.5-mg/24-h rivastigmine patch for at least 8-weeks at week 24. Secondary ...
To understand more fully the mechanism of enzyme-catalyzed phospho group transfer, the stereochemical course at phosphorus of four enzymes has been determined. First, using adenosine (..gamma..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)triphosphate as the substrate, the reaction catalyzed by creatine kinase has been found to proceed with overall inversion of configuration at phosphorus. Second, using adenosine (..beta..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)diphosphate as the substrate, the reaction catalyzed by adenylate kinase has been found also to proceed with overall inversion. Third, the reaction catalyzed by phosphoenolpyruvate carboxylase has been studied using ((S/sub p/)-/sup 16/O, /sup 17/O)thiophospoenolpyruvate as the substrate in H/sub 2/ /sup 18/O. Fourth, using adenosine 5'-O-((..gamma..S/sub p/)-..beta gamma..-/sup 17/O,..gamma..-/sup 17/O,/sup 18/O)(3-thiotriphosphate) as the substrate, the reaction catalyzed by pyruvate ...
Purpose: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. Methods and Materials: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. Results: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue of Group 2 patients showed similar pattern levels (high and low) as that of superoxide dismutase/catalase. The association of ...
Phosphoenolpyruvate carboxykinase (GTP) (PEPCK) specifically utilizes a guanosine or inosine nucleotide as a substrate, yet it does not share extended sequence homology with other GTP-binding proteins, and the molecular basis for its nucleotide specificity is not understood. In an effort to locate the enzyme's nucleotide-binding site, the authors have studied the interaction of cytosolic PEPCK from rat liver with the photoprobe 8-azidoGTP, which fulfills the criteria of a specific photoaffinity label for PEPCK. The photoprobe binds reversibly to the enzyme prior to modification and at low concentrations causes greater than 60% inactivation-GTP provides nearly complete protection against inactivation by 8-azidoGTP, whereas phosphoenolpyruvate and metal ions provide partial protection. In addition, the photoprobe is a substrate for the enzyme and has a K_m similar to that for GTP. However, the extent of covalent modification ...
Phosphoenolpyruvate carboxykinase (GTP) (PEPCK) specifically utilizes a guanosine or inosine nucleotide as a substrate, yet it does not share extended sequence homology with other GTP-binding proteins, and the molecular basis for its nucleotide specificity is not understood. In an effort to locate the enzyme's nucleotide-binding site, the authors have studied the interaction of cytosolic PEPCK from rat liver with the photoprobe 8-azidoGTP, which fulfills the criteria of a specific photoaffinity label for PEPCK. The photoprobe binds reversibly to the enzyme prior to modification and at low concentrations causes greater than 60% inactivation-GTP provides nearly complete protection against inactivation by 8-azidoGTP, whereas phosphoenolpyruvate and metal ions provide partial protection. In addition, the photoprobe is a substrate for the enzyme and has a K{sub m} similar to that for GTP. However, the extent of covalent ...
Based on their interesting properties, metal nanoparticles show the potential as an analytical tool in electronic (Burmeister et al. 2004), optical (Yguerabide and Yguerabide 1998), and catalytic applications (Liu 2006). Their characteristics depend on the composition, shape, and size of the single particles. These various properties are utilized in many different approaches such as optics, magnetics (Lang et al. 2007), and laser technology (Csaki et al. 2007). We investigated an alternative method for the synthesis of nanoparticles. In this case, an enzyme, horseradish peroxidase, induces a silver deposition and replaces a metal nanoparticle as the reaction seed. Depending on the reaction time, we could obtain particles in a range of few nanometers up to more than 250 nm. For a better understanding of the enzymatic silver deposition process, the silver particles produced by this process were analyzed by SEM, TEM, and atomic force microscopy (AFM) on a single ...
Glucoamylase and pullulanase were immobilized on reconstituted bovine-hide collagen membranes using the covalent azide linkage method. A pretanning step was incorporated into the immobilization procedure to enable the support matrix to resist proteolytic activity while accommodating an operating temperature of 50 degrees C. The immobilized glucoamylase and pullulanase activities were 0.91 and 0.022 mg dextrose equivalent (DE) min(-1) cm(-2) of membrane, respectively. Immobilized glucoamylase had a half-life of 50 days while the immobilized pullulanase had a half-life of 7 days. This is a considerably improved stability over that reported by other researchers. The enzymes were studied in their free and immobilized forms on a variety of starch substrates including waxy maize, a material which contains 80% alpha-1-6-glucosidic linkages. Substrate concentrations ranged from 1% to a typical commercial concentration of 30%. Conversion efficiencies of 90-92% DE were ...
Four extracellular keratinases (designated KI, KII, KIII, and KIV) were produced during submerged aerobic cultivation in a medium containing native human foot skin (NHFS) for enzyme synthesis. The molecular weights, determined by SDS-PAGE, were 25, 50, 34, and 19kDa, respectively. Gel filtration of the four purified enzymes in native conditions indicated that active keratinase KI is a novel homo-octamer, KII a homo-dimer, and KIII and KIV monomers. All four keratinases exhibited high activities at pH 8.0-10.0 with an optimal pH of 9.0. The optimal temperature for keratinolytic activity of KI, KII, and KIII was approximately 50, and 60degreeC for KIV. One millimolar of PMSF completely inhibited the keratinolytic activities of the four enzymes. The N-terminal sequences of KI, KII, and KIII s...
Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH (Gly(150)-Lys(190)) is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein ...
The goal of the present study is to elucidate the effect of lipid domain formation on activities of Naja naja atra and Bungarus multicinctus phospholipase A(2) (PLA(2)) enzymes. Sphingomyelin inhibited enzymatic activity and membrane-damaging activity of PLA(2) against egg yolk phosphatidylcholine (EYPC), while cholesterol and cholesterol sulfate abrogated the inhibitory effect of sphingomyelin. The ability of cholesterol and cholesterol sulfate to abolish the inhibitory effect of sphingomyelin was closely related to their capacity to induce domain formation in EYPC/sphingomyelin vesicles. Laurdan fluorescence measurement revealed that membrane packing of EYPC/sphingomyelin vesicles was differently affected by cholesterol and cholesterol sulfate. Unlike cholesterol, cholesterol sulfate was unable to promote domain formation in dipalmitoylphosphatidylcholine (DPPC) vesicles. Cholesterol increased but cholesterol sulfate reduced PLA(2) activity against DPPC. ...
Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C{sup {r_arrow}}T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C{sup {r_arrow}}T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C{sup {r_arrow}}T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD. 13 refs., 1 fig., 1 tab.
Acetaminophen (APAP) overdose, which causes liver injury in animals and humans, activates c-jun N-terminal kinase (JNK). Although it was shown that the JNK inhibitor SP600125 effectively reduced...Full Text Available
BackgroundThe status of estrogen receptor-α (ERα) is critical to the clinical prognosis and therapeutic approach in breast cancer. ERα-negative breast cancer...Full Text Available
In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell migration and MMP-2 activity as well as the ...
Two novel crystal structures of Zea mays protein kinase CK2α catalytic subunit, one in complex with the specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) and another...Full Text Available
Azobenzene dyes are effective inhibitors for austenitic 304 L and 316 L stainless steel corrosion in high acidic medium up to 7N. A good efficiency is obtained from weight loss and electrochemical Rsub(p) measurements in hydrochloric acid, while no inhibition is observed in sulfuric solutions. Transformation from the primarily azobenzene to other compounds give rise to enhanced protection of steel samples, and probable structures of the inhibiting species are proposed in view of our results.
Azobenzene dyes are effective inhibitors for austenitic 304 L and 316 L stainless steel corrosion in high acidic medium up to 7N. A good efficiency is obtained from weight loss and electrochemical Rsub(p) measurements in hydrochloric acid, while no inhibition is observed in sulfuric solutions. Transformation from the primarily azobenzene to other compounds give rise to enhanced protection of steel samples, and probable structures of the inhibiting species are proposed in view of our results.
Spectrophotometric method, using a ratio-recording ultraviolet-absorption spectrophotometer, permits analysis of NaMBT in ethylene glycol-water solutions with high accuracy. It reduces analysis time, requires smaller samples, and is able to detect extremely small concentrations of mercaptobenzothiazole.
Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21Waf1/Cip1/Sdi1 (p21), a known regulator...Full Text Available
1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase ...
1. We studied the effects of flash photolysis on the novel enantiomeric cardiac inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III inhibitor) in rat isolated ventricular...Full Text Available
Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group ...
Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)
We have demonstrated that the 80 kDa POP Tc80 (prolyl oligopeptidase of Trypanosoma cruzi) is involved in the process of cell invasion, since specific inhibitors block parasite...Full Text Available
In the aim to fight against tubes corrosion of geothermal wells which exploit the aquifer of Dogger reservoir in the Parisian basin, injection of corrosion inhibitors in the geothermal fluid has been generalized since 1989 by using an additive injection tube in the bottom of the well, allowing the protection of the two wells from the geothermal doublet. 3 annexes. 46 refs. 13 tabs. 9 figs.
Although matrix metalloproteinase-9 (MMP-9) is involved in cardiomyocytes contractility dysfunction, tissue inhibitor of metalloproteinase-4 (TIMP-4) mitigates the effect of MMP-9, and proteinase-activated...Full Text Available
N-Hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine (HET0016) is a potent inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific cytochrome P450 (CYP) isoforms....Full Text Available
AbstractThe gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations...Full Text Available
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not significantly impair T cell ...
The effect of WC particle size with the addition of VC as a grain growth inhibitor was investigated during the liquid phase sintering of WC-Co system. With increasing WC particle size at the same VC content, the effect of grain growth inhibition was increased. Also, with increasing the VC content, the grain shape of WC was changed from the faceted shape to the distorted shape, and the step density of the WC grain was increased. (orig.)
The p90 ribosomal S6 kinases (RSKs) also known as MAPKAP-Ks are serine/threonine protein kinases that are activated by ERK or PDK1 and act as downstream effectors of mitogen-activated protein kinase...Full Text Available
Antimicrobial susceptibilities of 233 Gram-positive and 180 Gram-negative strains to two novel bis-indoles were evaluated. Both compounds were potent inhibitors of Gram-positive bacteria, with MIC90...Full Text Available
BackgroundPulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27kip1, one of critical cyclin-dependent kinase inhibitors, has been...Full Text Available
This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available
Barley (Hordeum vulgare L. cv Golden Promise) plants were grown in a continuous culture system in which the root and shoot ammonia and amino acid levels were constant over a 6-hour...Full Text Available
1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available
1,1-Dichloroethylene is reported to produce renal tumors in male mice. It is an hepatotoxin in fasted rats after inhalation. We found that trichloropropane epoxide, an inhibitor of epoxide hydrase,...Full Text Available
In Indian traditional medicine, various plants have been used widely as a remedy for treating snakebites. The aim of this study was to evaluate the effect of Tamarindus indica seed extract on the pharmacological as well as the enzymatic effects induced by V. russelli venom. Tamarind seed extract inhibited the PLA2, protease, hyaluronidase, L-amino acid oxidase and 5prime-nucleotidase enzyme activities of venom in a dose-dependent manner. These are the major hydrolytic enzymes responsible for the early effects of envenomation, such as local tissue damage, inflammation and hypotension. Furthermore, the extract neutralized the degradation of the Bb chain of human fibrinogen and indirect hemolysis caused by venom. It was also observed that the extract exerted a moderate effect on the clotting ...
The removal phenol and 2-chlorophenol using soybean seed-hulls in the presence of hydrogen peroxide was demonstrated. The performance of a stirred membrane reactor containing soluble purified SEP was compared with a batch stirred reactor containing raw soybean seed-hulls. The purified enzyme reactor proved to be ineffective while good results were obtained with the crude seed-hulls for the removal of phenol and 2-chlorophenol. A single batch reactor containing raw seed-hulls was effective in removing more than 98.5% of 2-chlorophenol (initially at 10000 ppm) in less than 15 min. The performance of these rectors is comparable to existing HRP-based technology. The stability of the soybean peroxidase (SBP) enzyme was also examined in the presence of detergents (SDS, Tween 20 and Triton X-100).
Abstract A highly efficient enzyme immobilization method has been developed for electrochemical biosensors using polydopamine films with gold nanoparticles (AuNPs) embedded. This simple enzyme fabrication method can be performed in very mild conditions and stored in a long time with high bioactivity. The fabricated amperometric glucose biosensor exhibited a high and reproducible sensitivity, wide linear dynamic range and low limit of detection (LOD) (0.1 molL-1). A low value of 1.5 mmolL-1 for the apparent Michaelis-Menten constant KappM was obtained. The high sensitivity, wide linear range, good reproducibility and stability make this biosensor a promising candidate for portable amperometric glucose biosensor.
A practical hands-on course encompassing enzyme purification, biochemical characterization, and crystallization that completed the course work of 350 second-year bachelor students enrolled in molecular biology/biochemistry was given at the Universite Louis Pasteur of Strasbourg (France). The experimental part of the practical dealt entirely with the model protein lysozyme isolated from hen egg-white. It was designed as a research project to give students the possibility to practice biochemical methods such as chromatography, electrophoresis, and spectrophotometry. It also included enzyme activity assay and protein crystal growth that are usually taught in master-level courses. The organization of the practical work and the related experimental procedures are described and discussed.
Date palm (Phoenix dactylifera) is widely cultivated in Kutch district of Gujarat and the fruits are harvested at immature stage before the onset of monsoon to prevent spoilage. The immature date fruits with less commercial value were used for processing into date juice concentrate. Immature dates were crushed and treated with 0.1% pectinase enzyme for 120 min to obtain maximum juice. Date juice was found to be rich in reducing sugars (16.1%) and total sugars (18.3%). Juice was pasteurized at 85?C to inactivate the enzyme, cooled and centrifuged at 3000 rpm to get clear juice. The juice was concentrated in a thin film evaporator to a total soluble solids (TSS) of 76?Brix in 2 passes. Chemical composition of date juice during different stages of concentration was determined. Date juice conc...
Ethnopharmacological relevance: Tong Luo Jiu Nao (TLJN) is a modern Chinese formula based on Traditional Chinese Medicine theory that has been used to treat ischemic cerebral stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanism of the TLJN effect on Alzheimer's disease (AD). Aim of the study: To investigate the effect of TLJN on b-amyloid-degrading enzymes and learning and memory in the AD rat brain. Materials and methods: AD rats whose disease was induced by Ab25-35 injection into the bilateral hippocampus CA1 region were subjected to intragastric administration of various preparations. The experimental animals were healthy male Sprague-Dawley rats which were randomly divided into normal, sham, model, TLJN...
Salt stress elicits betaine accumulation to high levels in species from several diverse dicot families (Chenopodiaceae, Amaranthaceae, Convolvulaceae, Solanaceae, and Asteraceae). FAM-MS studies with deuterated precursors showed that species from all these families synthesize betaine from choline. Enzyme assays and immunotitration data showed that all accumulating species contained betaine aldehyde dehydrogenase (BADH) enzyme activity recognized by antibodies raised against purified BADH isolated from Spinacia oleracea. Immunoblotting indicated that the BADH monomer was in all cases of Mr {approx} 63,000. The similarity of BADH in the different species is consistent with a single evolutionary origin for the betaine pathway. This was supported by the presence in immunoblots of a cross-reacting band at Mr {approx} 63,000 in Magnolia x Soulangiana, a primitive angiosperm.
Thirty bacterial isolates were obtained from different sources and sites at Jeddah, Saudi Arabia, on chitin agar medium; 9 of the 30 isolates were cultured in liquid medium containing chitin as sole carbon and nitrogen sources. Isolate SM21, which was isolated from shrimp shells, showed the best growth and chitinase production in liquid medium. According to its morphological, physiological and biochemical characteristics, SM21 belongs to the genus Streptomyces and was identified as Streptomyces anulatus SM21. Identification was confirmed using 16S rDNA analysis. The chitinase enzyme was precipitated with 80% NH4SO4 and purified using DEAE-cellulose ion exchange chromatography followed by Sephadex G-100 gel filtration. The molecular weight determined using sodium dodecyl sulfate polyacrylam...
Skim natural rubber latex is a protein-rich byproduct obtained during the centrifugal concentration of natural rubber latex. Skim latex has a very low dry rubber content (4-8%), and the rubber particles are smaller in size. It has a higher proportion of nonrubber solids, which are mostly proteinaceous in nature. It is difficult to coagulate, and it takes more processing time. The proteins in skim latex can be decomposed by proteolytic enzymes. This article discusses the use of stabilized liquid papain from the papaya plant (Carica papaya) for deproteinization followed by creaming for quick and easy coagulation of skim latex. The technological properties and aging characteristics of the deproteinized skim rubber are compared with those of conventionally prepared skim rubber and block rubber...
Cellulose sausage cellulose casings are used extensively in the manufacture of sausages in meat packaging. After stripping the meat, spent casings mainly contain cellulose and residual meat juice with salt, nitrate and nitrite. Disposal of spent sausage casings has serious economic and environmental concerns for the sausage industry. This work describes bioconversion of spent cellulose casings (SCC) into enzymes, lactic acid and ethanol by using cellulolytic fungi, lactobacillus and yeasts. The solid substrate cultivation (SSC) of Trichoderma reesei RUT C-30 on SCC and blends gave a maximum of 152 filter paper cellulase (FPase) activity and about 100 carboxymethylcellulase activity (CMCase)/g dry weight substrate. The SSC produced enzyme-rich casing with 50 FPase when directly mixed as suc...
The production of {alpha}-amylase by Bacillus licheniformis M27 in submerged fermentation was completely inhibited due to catabolic repression in medium containing 1% glucose. In contrast, the enzyme production in a solid state fermentation system was 19,550 units/ml extract even when the medium contained 15% glucose. The peak in enzyme titre was, however, shifted from 48 to 72 h. The ability of the solid state fermentation system to significantly overcome catabolic repression was not known earlier and is probably conferred by various physico-chemical factors and culture conditions specific to the system. (orig.).
Uridine phosphorylase (UPP) catalyzes the reversible conversion of uridine to uracil and ribose-1-phosphate and plays an important pharmacological role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil and capecitabine. Most vertebrate animals, including humans, possess two homologs of this enzyme (UPP1 & UPP2), of which UPP1 has been more thoroughly studied and is better characterized. Here, we report two crystallographic structures of human UPP2 (hUPP2) in distinctly active and inactive conformations. These structures reveal that a conditional intramolecular disulfide bridge can form within the protein that dislocates a critical phosphate-coordinating arginine residue (R100) away from the active site, disabling the enzyme. In vitro activity measurem...
A method for product analysis that eliminates a problematic step in the radiometric sucrose-phosphate synthase assay is described. The method uses chromatography on a boronate-derivatized high-performance liquid chromatography column to separate the labeled product, (14C)sucrose phosphate, from unreacted uridine 5{prime}-diphosphate-(14C)glucose (UDP-Glc). Direct separation of these compounds eliminates the need for treatment of the reaction mixtures with alkaline phosphatase, thereby avoiding the problem of high background caused by contaminating phosphodiesterase activity in alkaline phosphatase preparations. The method presented in this paper can be applied to many UDP-Glc requiring enzymes; here the authors show its use for determining the activities of sucrose-phosphate synthase, sucrose synthase, and uridine diphosphate-glucose pyrophosphorylase in plant extracts.
The following topics are discussed: insertion of incorrect bases in DNA; ability of DNA polymerase to copy uv-irradiated DNA; role of enzymes in repair of DNA; effects of uv radiation on molecular weight of DNA; photoreactivation; repair of DNA in Escherichia coli and xp cells following uv radiation; and synchrotron radiation studies on DNA repair. (HLW)
Because of variations in tRNA sequences in evolution, tRNA synthetases either do not acylate their cognate tRNAs from other organisms or execute misacylations which can be deleterious in vivo. We report...Full Text Available
Studies of ribulose-1,5-bisphosphate (RuBP) carboxylase from taxonomically diverse plants show that the enzyme from C3 and crassulacean acid metabolism pathway species exhibits lower Km(CO2)...Full Text Available
Cell-free extracts of Acremonium chrysogenum and Streptomyces clavuligerus oxidize the 3-methyl group of desacetoxycephalosporin C to a 3-hydroxymethyl group. The enzyme responsible for this reaction...Full Text Available
The effects of bivalent cations on cytochrome b5 reduction by NADH:cytochrome b5 reductase and NADPH:cytochrome c reductase were studied with the proteinase-solubilized enzymes. Cytochrome b5 reduction...Full Text Available
Nucleotide pool sanitizing enzymes Dut (dUTPase), RdgB (dITPase), and MutT (8-oxo-dGTPase) of Escherichia coli hydrolyze noncanonical DNA precursors to prevent incorporation of base...Full Text Available
In this study, six groups of rats were fed as follows: Groups 1 and 2 were fed formulated diets supplemented with zinc or without zinc respectively. Groups 3 and 4 were fed formulated diets supplemented with zinc plus phytic acid extracted from sweet potato (Ipomea batatas) or commercial phytic acid respectively. Groups 5 and 6 were fed formulated diets supplemented with phytic acid extract from sweet potato or commercial phytic acid respectively. The animals were fed for three weeks and then sacrificed The activities of key enzymes of carbohydrate and lipid metabolism as well as transaminases in the liver were determined. Blood glucose level was also assessed. Phytic acid extract consumption from sweet potato and commercial phytic acid plus zinc supplement lowered blood glucose levels. There was no significant change in the activity of 6-phosphogluconate dehydrogenase among the groups. Similarly, phytic acid supplementation showed no significant decrease in the ...
A soluble enzyme system from suspension cultures of Acer pseudoplatanus L. converts d-glucose 6-phosphate to myoinositol. A Mg2+-dependent phosphatase, present in...Full Text Available
The protein “amplified in osteosarcoma-9” (OS-9) has been shown previously to interact with the prolyl hydroxylases PHD2 and PHD3. These enzymes initiate oxygen-dependent degradation...Full Text Available
A two-step purification protocol was used in an attempt to separate the constitutive NAD(P)H-nitrate reductase [NAD(P)H-NR, pH 6.5; EC 1.6.6.2] activity from the nitric oxide and nitrogen dioxide (NO(x))...Full Text Available
Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X...Full Text Available
An assay method is described for measurement of absolute concentrations of the molybdenum cofactor, based on complementation of the defective nitrate reductase ('apo nitrate reductase') in extracts...Full Text Available
Renewable energy sources have received increased interest from the international community with biomass being one of the oldest and the most promising ones. In the concept of exploitation of agro-industrial residues, the present study investigates the pre-treatment and ethanol fermentation potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic durations have been tested. Both wet oxidation and enzymic treatment were evaluated based on the ethanol obtained in a subsequent fermentation step by Saccharomyces cerevisiae and Thermoanaerobacter mathranii. It was found that a four-day hydrolysis time was adequate for a satisfactory release of glucose and xylose. The combination of wet ...
Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
BackgroundPlasmid encoded blaCTX-M enzymes represent an important sub-group of class A β-lactamases causing the ESBL phenotype which is increasingly...Full Text Available
Biological cells of the nitrogen fixating bacteria Xanthobacter autotrophicus GZ 29 have been cultivated with 57-Fe, and from the nitrogenase of these cells the 57-Fe marked molybdenum-iron-protein is extracted. The Moessbauer spectra of this enzyme show that the structure of the iron cluster is similar to the structure in the molybdenum-iron-proteins of Azotobacter vinelandii, Klebsiella pneumoniae or Clostridium pasteurianum.
1. A cell-free system, prepared from Pseudomonas N.C.I.B. 9340 grown on 4-chloro-2-methylphenoxyacetate (MCPA) was shown to catalyse the reaction sequence: 5-chloro-3-methylcatechol...Full Text Available
Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. 37 refs., 7 figs., 3 tabs.
... The larvae's only hope for survival is if the antibiotic tetracycline is present -because it mops up the enzyme. The developers hope male GM mosquitoes will compete with normal males for females so that repeated releases cut numbers of A. aegypti in dengue-prone areas. The mosquitoes will be released in the inland districts of Bentong in the state of Pahang, and Alor Gajah and Melaka in the state of Malacca, according to the National Biosafety Board. Each location will have two release phases: the first at a site ...
Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the pathogenesis of atherosclerosis and post-angioplasty restenosis. In the present study, we designed locked nucleic...Full Text Available
Enzyme-linked immunosorbent assays for the detection of immunoglobulin M (IgM), IgA, IgG1, and IgG2 antibodies against bovine respiratory syncytial virus (BRSV) were used to measure antibody responses...Full Text Available
Previous DNA relatedness and enzyme electrophoretic mobility studies indicated heterogeneity among strains of Legionella pneumophila serogroups 1, 4, 5, and Lansing 3 (a new, as yet unnumbered serogroup)....Full Text Available
Two nitrate reductase deficient mutants of soybean (Glycine max [L.] Merr. cv Bragg) were isolated from approximately 10,000 M2 seedlings, using a direct enzymic assay in...Full Text Available
Sequence-specific interactions between aminoacyl-tRNA synthetases and their cognate tRNAs both ensure accurate RNA recognition and prevent the binding of noncognate substrates. Here we show for Escherichia...Full Text Available
... The male GM mosquitoes mate with normal females to produce larvae that die unless the antibiotic tetracycline is present. In tetracycline's absence an enzyme accumulates to a toxic level, killing the larvae. The developers hope the strategy could be combined with other mosquito control methods to reduce transmission in dengue-prone areas. Ricarda Steinbrecher, a geneticist and co-director of EcoNexus -a UK-based non-profit research organisation -expressed surprise ...
... The male GM mosquitoes mate with normal females to produce larvae that die unless the antibiotic tetracycline is present. In tetracycline's absence an enzyme accumulates to a toxic level, killing the larvae. The developers hope the strategy could be combined with other mosquito control methods to reduce transmission in dengue-prone areas. Ricarda Steinbrecher, a geneticist and co-director of EcoNexus - a UK-based non-profit research organization - ...
AbstractWe describe the fusion of enhanced green fluorescent protein to the C-terminus of the HsdS DNA sequence-specificity subunit of the Type I DNA modification methyltransferase M.EcoKI....Full Text Available
Acyl-CoA:diacylglycerol acyltransferase (EC 2.3.1.20) is a membrane protein present mainly in the endoplasmic reticulum. It catalyzes the final and committed step in the biosynthesis of triacylglycerol,...Full Text Available
BackgroundResistance to third generation cephalosporins due to acquisition and expression of extended spectrum β-lactamase (ESBL) enzymes among Gram-negative bacteria is...Full Text Available
DescriptionThe plant enzyme polyphenol oxidase (PPO) has been demonstrated to reduce both proteolysis and lipolysis during the ensiling of red clover. The purpose of this work is to explore the potential for exploiting this beneficial trait in other dietary regimes for grazing ruminants. These studies will focus on the development of new strategies for forage management and livestock feeding by increasing the efficiency of feed protein-N utilisation and reducing saturated fatty acid production by ruminan [continued...
The previously described (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol., 31:947-954, 1993) a362 recombinant polypeptide of Mycobacterium paratuberculosis was used...Full Text Available
The use of β-lactam antibiotics has led to the evolution and global spread of a variety of resistance mechanisms, including β-lactamases, a group of enzymes that degrade the β-lactam...Full Text Available
The nr1 soybean (Glycine max [L.] Merr.) mutant does not contain the two constitutive nitrate reductases, one of which is responsible for enzymic conversion of nitrite to...Full Text Available
Most chemical reactions in industry and biology are catalytic and play a role at some stage of the processing of about 80% of the goods manufactured in the U.S., yet catalysis is a neglected subject in chemical education. This book integrates the fragmentary treatment accorded the topic until now. It covers, in a unified way, catalysis in solutions, by enzymes, in synthetic polymers within the molecular scale cages of zeolites and other molecular sieves, and on surfaces of inorganic solids. The central ideas are chemical; and principles are illustrated by emphasizing industrial reactions and catalysts.
The gene Rv1885c from the genome of Mycobacterium tuberculosis H37Rv encodes a monofunctional and secreted chorismate mutase (*MtCM) with a 33-amino-acid...Full Text Available
This study investigated the effects of electromagnetic fields on enzymes involved in purine metabolism in human peripheral blood mononuclear cells in vitro. Cells were obtained from 20 volunteers. We...Full Text Available
Suicide substrate β, γ-bidentate Rh(III)ATP (RhATP) was used to map the metal ion-binding site in yeast phosphoglycerate kinase (PGK). Cleavage of the RhATP-inactivated enzyme with...Full Text Available
Ethylene (C2H4) is a unique plant-signaling molecule that regulates numerous developmental processes. The key enzyme in the two-step biosynthetic pathway of ethylene is 1-aminocyclopropane-1-carboxylate...Full Text Available
The availability of rice, gamma -irradiated up to 4.6 x 10/sup 4/ and 3.5 x 10/sup 5/r for koji was studied. The enzyme activities of koji of the steamed samples were stronger than the unirradiated rice in amylase and protease. The sensory test on the once-steamed irradiated rice was almost the same as the twice-steamed unirradiated rice. (OID)
Plerocercoids of the tapeworm Spirometra mansonoides produce a substance that stimulates growth of experimental hosts. We report purification of plerocercoid growth factor (PGF) to homogeneity by a process involving isolation and solubilization of plerocercoid membranes, isoelectric point selection by chromatofocusing chromatography or preparative isoelectric focusing, and anion-exchange chromatography. A radioreceptor assay (RRA) for human growth hormone (hGH) was used to detect PGF and purity of the 27.5-kDa protein was judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Proteolytic activity was detected in the 27.5-kDa protein by gelatin substrate PAGE. Characterization of PGF as a neutral cysteine proteinase was based on substrate and inhibitor specificities and dependence on pH and thiol-containing reagents. The association of hGH agonist and proteinase activities was shown by comparing RRA and hydrolytic activities in the presence ...
The authors investigated the effect of T-2 toxin on rat liver mitochondrial protein synthesis. Isolated rat liver mitochondria were supplemented with an S-100 supernatant from rat liver and an external ATP-generating system. An in-vitro assay employing cycloheximide, and inhibitor of cytoplasmic protein synthesis, and chloramphenicol, and inhibitor of mitochondrial protein synthesis, to distinguish mitochondrial protein synthesis from the cytoplasmic process. Amino acid incorporation into mitochondria was dependent on the concentration of mitochondria and was inhibited by chloramphenicol. The rate of uptake of tritium leucine into mitochondrial protein was unaffected by the addition of T-2 toxin and was not a rate-limiting step in incorporation. However, 0.02 micrograms/ml of T-2 toxin decreased the rate of protein synthesis inhibition correlated with the amount of T-2 toxin taken up by the mitochondria. While T-2 toxin is known to inhibit ...
Erectile dysfunction following radical prostatectomy remains a frequent problem despite the development of nerve-sparing techniques. This erectile dysfunction is believed to be neurogenic, enhanced by hypoxia-induced structural changes which result in additional veno-occlusive dysfunction. Recently, daily use of intracavernous vasoactive substances and oral use of PDE5-inhibitors have been clinically studied for treatment of postprostatectomy erectile dysfunction. Since these studies showed benefits of "penile rehabilitation therapy," these effects have been studied in a preclinical setting. We reviewed experimental literature on erectile tissue preserving and neuroregenerative treatment strategies, and found that preservation of the erectile tissue by the use of intracavernous nitric oxide donors or vasoactive substances, oral PDE5-inhibitors, and hyperbaric oxygen therapy improved erectile function by antifibrotic effects and preservation of ...
Metal cations of arsenic, antimony, tin, manganese, zinc, cadmium, indium, and thallium have been evaluated in a preliminary way as possible3 inhibitors for controlling denting corrision observed in steam generators used with pressurized water reactors (PWR). The rationale for this approach was based upon the well-known inhibition effects of metal cations on corrosion rates in electrolyte/metal systems. A review of corrosion inhibition by metal cations (H. Leidheiser, Jr., Corrosion 36, 339 (1982)) has identified eleven inhibition mechanisms. The major test methods used for this evaluation were: (1) Isothermal capsule tests of carbon/steel/Inconel 600 tube bulging rates at temperatures up to 288/sup 0/C in seawater/copper-nickel chloride bulge-accelerating solutions. (2) Immersion weight-loss tests of steel coupled to Inconel 600 in boiling (102/sup 0/C) 3% sodium chloride solutions. In addition, electrochemical measuremens and surface analyses were performed. The ...
Weight loss measurements were performed in 20% and 28% hydrochloric acid at 90/sup 0/C on carbon steel, 22Cr5Ni duplex stainless steel, and two superaustenitic steels - 27Cr31Ni3Mo and 19Cr25Ni4Mo -, in presence of organic substances used singly or mixed. The organic substances examined were quaternary ammonium salts (1-4-pyridyl)-pyridinium chloride hydrochloride, dodecylpyridiniumchloride, benzyldimethylstearylammonium chloride, and dodecyltrimethylammonium bromide), alkynols (1-octyn-3-ol, propargyl alcohol) and trans-cinnamaldehyde. The synergistic effect of potassium iodide on the inhibitive efficiency of the organic substances was studied. The variations of corrosion rate during the test time (normally six hours) were recorded by means of polarization resistance measurements. Polarization curves were also recorded. The results showed that the corrosion rates of the four steels examined can be reduced to less than 1 mg/cm/sup -2/ . h/sup -1/ using ternary ...
Chloride-induced pitting corrosion of stainless steel (Materials No. 1.4301 and 1.4571) was investigated with the aid of chronopotentiostatic tests. Oxide films upon the surface (temper colours), addition of inhibitors (sulphate and nitrate) and temperature were the testing variables. Two different critical pitting potentials have been found, which give information on the potential ranges for stable passivity, latent and stable pitting corrosion. The results only indicate a small effect of Mo content of the material and test temperature. The inhibitors (sulphate and nitrate) have a marked effect. Specimens with a clean surface produced by pickling are markedly more resistant against pitting corrosion than specimens with a yellow temper colour, whereas the difference in corrosion resistance between yellow and blue films is relatively small. The width of the critical potential range for pitting corrosion generally increases with increasing oxide ...
The structural organization of the genes encoding Bungarus multicinctus protease inhibitor-like proteins (PILPs), PILP-1, PILP-2 and PILP-3, are reported in this study. Unlike PILP-2 and PILP-3, recombinant PILP-1 exhibited inhibitory activity on trypsin. PILP genes and B chain genes shared identical organization with three exons interrupted by two introns in similar positions. On the contrary, intron 1 of these genes had a similar size, a notable variation with the size of intron 2 was observed. It was found that two regions at the second intron of B1 chain and B2 chain genes were absent in that of PILP genes. Noticeably, intronic insertion in the second intron of B chain genes appeared in the promoter region of PILP-1 gene, but not in that of PILP-2 and PILP-3 genes. Comparative analyses of PILP genes and B chain genes showed that the protein-coding regions of the exons are more diverse than introns, except for in the signal peptide domain. These results suggest ...
The corrosion inhibition of C38 steel in molar HCl by N,N-bis[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]buthylamine (P1) and 5-{N,N-bis[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl] amino} pentanol (P2) has been investigated at 308?K using electrochemical and weight loss measurements. Measurements show that these compounds act as good inhibitors without changing the mechanism of the corrosion process. Moreover, the inhibiting efficiency increases with the increase in concentration of the studied inhibitors. Compound P2 showed better protection properties even at relatively higher temperatures when compared to P1. The associated activation corrosion and free adsorption energies have been determined. P1 and P2 are adsorbed on the C38 steel surface according to a Langmuir isotherm adsorption model.
Stereoselective methods for synthesising iminoalditols are still needed, as this class of compounds is known to contain strong glycosidase inhibitors. We have for some time investigated (1) the possibilities for using 2-amino-6-bromo-2,6-dideoxy-aldonolactones as starting materials for such compounds, since a substitution at C-6 by the 2-amino group should lead to the target molecules. We have found that treatment of mentioned 2-aminolacones with aqueous base gave 5- or 6-membered iminoalditols depending of the stereochemistry of the lactone, while under non aqueous conditions only formation of 6-membered iminoalditols were observed. The use of triethylamine in methanol thus gave methylesters of 6-membered iminouronic acids. Reduction of the ester group with sodium borohydride gave the target compounds. The mechanisms of the reactions will be discussed as well as specific results obtained. (1) Lundt, I. Top. Curr. Chem. 1997, 187, 117-156
Abstract Purpose: To describe the pattern of expression of the cyclin-dependent kinase inhibitors (CDKIs) p16, p21 and p27, and the cell cycle in SRA 01/04 cells relative to contact inhibition. Methods: SRA 01/04 cells were grown to overconfluence under normal conditions. At various phases of the cell growth, cells were assayed by flow cytometry and Western blotting for the expression of CDKIs. Results: Expression of p16 was detected from early logarithmic growth to stationary phases, during which the number of cells in G0/G1 increased from 46 to 69%. Expression of p21 was detected only during the overgrowth phase, when 60% of the cells were in G0/G1. Expression of p27 was not observed in SRA 01/04 cells. Conclusions: p16 expression was likely mediated by G0/G1 arrest to induce contact inh...
BACKGROUND Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. We investigated the histone acetylation status in endometriosis and the application of the histone deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS The levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were evaluated. The effects of the HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and the expression of genes related to these cellular events were investigated. The effects of HDACIs on histone acetylation in chromatin of the promoter region of the cell cycle regulatory genes in ECSCs were also investigated. RESULTS The acetylated histone levels were significantly lower in ECSCs than in NESCs (P endometriosis and that HDACIs reactivated epigenetically silenced genes, resulting in the suppression of cell ...
The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Each time this trait evolves, novel solutions to the problem posed by vertebrate hemostasis are generated. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Molecular approaches (termed 'sialomics') to characterize the full inventory of mRNAs transcribed in salivary glands have revealed a surprising level of complexity within a single species. Multiple salivary proteins may be ...
Cyclothiazomycin B1 (CTB1) is an antifungal cyclic thiopeptide isolated from the culture broth of Streptomyces sp. HA 125-40. CTB1 inhibited the growth of several filamentous fungi including plant pathogens along with swelling of hyphae and spores. The antifungal activity of CTB1 was weakened by hyperosmotic conditions, and hyphae treated with CTB1 burst under hypoosmotic conditions, indicating increased cell wall fragility. CTB1-sensitive fungal species contain high levels of cell wall chitin and/or chitosan. Unlike nikkomycin Z, a competitive inhibitor of chitin synthase (CHS), CTB1 did not inhibit CHS activity. Although CTB1 inhibited CHS biosynthesis, the same result was also obtained with a non-specific proteins inhibitor, cycloheximide, which did not reduce cell wall rigidity. These ...
Investigations of sucrose synthase in maize root tips have required development of a means to circumvent the rapid decline of activity observed after extraction dialysis and either synthetic or degradative assays. Several protease inhibitors were tested; although PMSF increased initial activity, no inhibitor prevented the drop in activity with time. Western blot analysis indicated that activity decline was not associated with protein degradation. Therefore, a procedure was developed which (1) shortened extraction-to-assay period from ca. 24 hours to 7 minutes, (2) simplified previous assays and (3) reduced the amount of tissue required. Extract was desalted with spun columns and the {sup 14}C-UDPG product recovered with DEAE ion exchange paper. The minute quantities of product recovered can be concealed by the presence of trace impurities in the {sup 14}C-sucrose utilized. DEAE ion exchange paper was used to remove interfering radio-labelled ...
Niobium carbide can be used to inhibit WC grain growth in hardmetal. The performance of a NbC powder produced at low temperature by solid-gas reaction (an experimental powder) as WC grain growth inhibitor is compared with that of a commercial NbC powder. It is verified that NbC effectively inhibits heterogeneous WC coarsening. This results in an increase in hardness. The commercial and experimental NbC powders exhibit a comparable performance in inhibiting the WC grain coarsening, in spite of a significant difference in particle size and shape. The commercial NbC powder is very fine while the experimental one is coarse and porous, but its crystallites are finer than those of the commercial product. The milling procedure used to prepare the alloys is able to reduce the particle size of the experimental NbC, and thus guarantee a dispersion of the particles with a quality level comparable to that found for the alloy prepared with the commercial NbC. (orig.)
Rare-earth oxides are doped into ZnO varistors as grain growth inhibitors for increasing the varistors' voltage gradients. However, their leakage currents become large and their nonlinear coefficients decrease at the same time. The reasonable explanation for such a phenomenon has not yet been available. In this paper, the temperature dependences of varistor samples' leakage currents are investigated, which reveal that the increased leakage currents of ZnO varistors with Y2O3 doping are mainly due to the bypass paths through the intergranular materials at grain corners.
The threshold stress intensities for stress corrosion crack propagation in beta titanium alloy 38-6-44, Ti3Al-8V-6Cr-4Mo-4Zr, has been determined in salt water and methanolic solutions. The alloy was immune to stress corrosion cracking (SCC) in aqueous sodium chloride solutions (marine atmosphere). However, in methanolic solutions, the alloy was very susceptible to SCC. This marked susceptibility in methanolic solutions can be mitigated by the addition of an inhibitor: sodium nitrate. Crack extension in the alloy was transgranular and failure occurred by brittle quasi-cleavage in methanolic solutions.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were measured in a mild case of dyssegmental dysplasia. X-ray pictures of a female baby born vaginally at 39 weeks of gestation showed short, bent, dumbbell-shaped long bones of the limbs and profound dyssegmental ossification in the spine, findings characteristic of dyssegmental dysplasia. When the levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured, the levels of MMP-2 and TIMP-1 were significantly reduced. This case might provide a clue to disclose the etiology of dyssegmental dysplasia. PMID:12568417
The present process allows to eliminate the corrosion products formed on the tube plates and in the interstices of plate-tube crosspieces of a PWR steam generator in order to avoid a corrosion phenomenon which may cause denting by presence of oxides. The process consists in applying on these oxides at about 50-100 degrees, an aqueous solution containing 6-8% of gluconic acid, 3-5% of citric acid, about 0.5% of a corrosion inhibitor and ammonia until a pH of 3-9.5 is obtained.
In this paper, an environmentally friendly metal corrosion inhibitor, phytic acid, was assembled into the walls of silica nanoparticles via layer-by-layer self-assembly technique (LbL) with poly(allylamine hydrochloride). Such functionalized nanoparticles were uniformly distributed into sol-gel films for metal anticorrosion. The films showed very pronounced and lasting protective efficiency in concentrated salt aqueous solutions as indicated by electrochemical impedance spectroscopy (EIS) measurement. These results may provide a new route for the preparation of environment-friendly anticorrosion coatings.
Doped ultrafine silicon dioxide powder with a narrow particle size distribution was obtained by RF discharge-stimulated dichlorosilane (SiH2C) oxidation at a low pressure using isobutylene as the combustion inhibitor and chromium hexacarbonyl (Cr(CO)6) as the dopant. The formation and morphology of the ultrafine particles are governed by the parameters of the RF discharge and by the chemical mechanism of the combustion reaction yielding the aerosol. Submicron-sized filamentous carbon structures can be obtained by isobutylene decomposition under spark discharge conditions in the presence of a molybdenum metal catalyst.
This paper reports the presence of face centered cubic cobalt precipitates inside tungsten carbide in nanocomposite of WC-Co synthesized by spray conversion processing. EDS was used to identify the presence and micro-diffraction was employed to determine the nature of the precipitates. There is entrapment of cobalt in tungsten carbide during the spray conversion process used to form WC/Co powder. During consolidation, at high temperatures, the cobalt attains enough mobility to precipitate inside WC. A vanadium containing compound was seen at the interfaces in samples which incorporated VC as a grain growth inhibitor. (orig.)
Those materials that can be extracted from pine or oak by ether, ethanol, methyl methacrylate (MMA), or benzene--alcohol all act as inhibitors in the #gamma# polymerization of MMA--wood composites. It was found that preirradiation of either the wood or of the wood--monomer combination reduces or eliminates the inhibitory effect. The most practical industrial solution to this problem is to increase the dose, thereby achieving high molecular polymer in the composite. However, the presence of a maximum in the molecular weight--dose curves means that each wood--monomer pair may have a different optimum dose.
Biosorption is an important removal mechanism in treating hydrophobic toxic organics in biological reactors. Equilibrium sorption isotherms and sorption kinetics of 2,4-dichlorophenol on live and chemically inactive anaerobic granules were studied. A metabolic inhibitor was used to inactivate the biological activity of the biomass. Results showed that the difference in the biosorption of live and chemically inactive anaerobic granules is not significant. This would suggest that anaerobic biosorption is mainly a physical-chemical process and that metabolic-mediated diffusion in the process is negligible. 12 refs., 3 tabs., 7 figs.
This paper describes an exact solution to the problem of absorbing nitrogen dioxide into aqueous solution, in which case the nitrogen dioxide concentration is allowed to vary over a wide range. The authors have worked on the rate of calcium sulfate dihydrate scale formation on the reverse osmosis membrane and find this phenomena can be treated by the crystallization theory. The authors performed long-term experiments using calcium sulfate dihydrate solution with addition of sodium hexametaphosphate (SHMP) and commercially available organophosphates and investigated the mechanism of the inhibitor's action quantitatively.
The adsorption and corrosion inhibition behavior of three selected thiosemicarbazone derivatives, namely 3-pyridinecarboxaldehyde thiosemicarbazone (META), isonicotinaldehyde thiosemicarbazone (PARA) and 2-pyridinecarboxaldehyde thiosemicarbazone (ORTHO) at the nickel surface were studied electrochemically by Tafel and impedance methods and computationally by carrying out Monte Carlo searches of configurational space on nickel/thiosemicarbazone derivative system. Electrochemical measurements showed that the inhibition efficiency of these compounds increased with increase in their concentration. The recorded inhibition efficiencies of the three tested thiosemicarbazone increase in the order: META>PARA>ORTHO. Polarization studies showed that these compounds act as mixed-type inhibitors for n...
To evaluate the effect of porosity on superplasticity behavior, it is essential to use materials of similar initial grain sizes. This can be achieved by HIPing, which provides an effective way of reducing initial porosity while avoiding appreciable grain growth; various levels of porosity can be achieved for similar grain sizes. This note is concerned with the influence of porosity on superplasticity tensile deformation of a fine grained high-purity alumina doped with copper oxide and containing a grain growth inhibitor. Specimens were prepared by slip casting to net-shape and sintering; some presintered specimens were HIPed to reduce porosity. The subsequent superplasticity behavior is related to porosity in the material.
The Purex process and the fluorescence spectrometry are first recalled, then uranyl fluorescence is studied in a pure nitric medium without other elements to establish a theoretical model, allowing the description of uranium fluorescence signal with a general equation. The influence of different parameters (temperature, inhibitors, dynamic quenching of iron and cerium) is investigated to develop the model. A quantitative analysis method without addition of reagents is proposed to validate the model.
Papers are presented under 38 symposia. Subjects included reinforced concrete, protective coatings and linings, cathodic/anodic protection, chemical cleaning of boilers, managing corrosion with plastics, water treatment, HRSG boiler tube failure analysis, corrosion in oil and gas production, corrosion in petroleum refining and gas, processing, pipelines and tanks, high temperature materials, chemical process industry, aerospace equipment, materials technology developments for incinerators and waste fuel-fired processors, materials and corrosion in fossil-fuels conversion and combustion, corrosion in nuclear systems, marine corrosion, building systems, corrosion mechanisms, corrosion inhibitors and corrosion monitoring and measurement.
Purpose - The purpose of this paper is to evaluate the corrosion inhibition potential of mangrove (Rhizopora apiculata) tannin in hydrochloric acid medium on copper with the view of developing a natural corrosion inhibitor. Design/methodology/approach - The mangrove tannin was extracted from the mangrove bark and its anticorrosion potential was studied by weight loss, electrochemical and scanning electron microscopy (SEM) analysis. Findings - It has been found that the mangrove tannin effectively inhibits the corrosion on copper metal in hydrochloric acid solution. The results of the electrochemical and weight loss methods showed that the inhibition efficiency of mangrove tannin increases with increasing its concentration. Inhibition is achieved through the adsorption of tannin molecules o...
The efficiency of NbC on WC grain coarsening in a WC-10wt.%Co hardmetal alloy was demonstrated by hardness measurement and WC granulation observation. The heterogeneous and overall grain growth were controlled. A low temperature experimentally produced NbC was used and compared to the inhibition potential of a commercial NbC powder. The results were the same in terms of structural fineness and hardness. The dispersion of the experimental NbC was not a problem, in spite of its size. The experimental NbC has very large particles, formed by agglomerates of small crystallites. During milling these agglomerates could be broken down. (orig.)
One rationale proposals to increase the efficiency of PDT is to combine photo-sensitization with other treatment modalities, including modulation of arachidonic acid metabolism. In combine treatment we examined the effects of 48 h and 24 h pre-treatment of cells with 5- lipoxygenase inhibitor MK-886 prior to photoactivation of hypericin on cell cycle distribution and DNA synthesis. All parameters were examined 24 hours after hypericin activation. Pre-treatment of HT-29 with 5-lipoxygenase inhibitor MK-886 followed by PDT resulted in most significant effects on cell cycle perturbations. Administration of MK-886 alone as well as combination of low doses MK-886 with hypericin induced S phase accumulation. Increasing of MK-886 concentration induced massive changes in the cell cycle progression. Pre-treatment of HT-29 cells with MK-886 alone (15 #mu#M; - 48 h) caused accumulation of cells in S-phase (58 % in S-phase and 36 % in G_0/G_1 phase). ...
Phlorizin is a competitive inhibitor of Na/sup +//glucose symport in animal cells and of H/sup +//3-O-methylglucose (3-O-MeG) symport in liverworts. The effects of this compound on the uptake of (U-/sup 14/C) sucrose and of (/sup 14/C) 3-O-MeG by broadbean (Vicia faba L.) leaf discs were studied. Leaf discs without lower epidermis were preincubated in the dark for 30 min (fresh discs) or for 12 h (aged discs) on a medium buffered at pH 5.0 containing mannitol as an osmoticum. They were then incubated for 30 min in the light on a similar solution added with 1 mM (/sup 14/C) sucrose or (/sup 14/C) 3-O-MeG and 5 mM phlorizin. Phlorizin inhibited uptake of 3-O-MeG by 37 and 50% respectively in fresh and aged discs. Sucrose uptake was more sensitive to the inhibitor than 3-O-MeG uptake and was also more inhibited in aged than in fresh discs (76% inhibition vs 54%). Kinetic studies showed that the inhibition exerted by phlorizin in fresh material is ...
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of proliferating cell ...
Sucrose phosphate synthase (SPS) catalyzes the transfer of a glycosyl group from an activated donor sugar, such as uridine diphosphate glucose (UDP-Glc), to a saccharide acceptor D-fructose 6-phosphate (F6P), resulting in the formation of UDP and D-sucrose-6'-phosphate (S6P). This is a central regulatory process in the production of sucrose in plants, cyanobacteria, and proteobacteria. Here, we report the crystal structure of SPS from the nonphotosynthetic bacterium Halothermothrix orenii and its complexes with the substrate F6P and the product S6P. SPS has two distinct Rossmann-fold domains with a large substrate binding cleft at the interdomain interface. Structures of two complexes show that both the substrate F6P and the product S6P bind to the A-domain of SPS. Based on comparative analysis of the SPS structure with other related enzymes, the donor substrate, nucleotide diphosphate glucose, binds to the B-domain of SPS. Furthermore, we propose a ...
In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane ...
Aminocyclopropane 1-carboxylic acid (ACC) synthase, a pyridoxal phosphate utilizing enzyme, catalyzes the conversion of S-adenosylmethionine to ACC, the rate limiting step in the biosynthesis of the plant hormone, ethylene. Ethylene, besides being involved in normal plant growth processes, is also produced in response to stress, e.g. wounding, pathogen infection, etc. The authors report the partial purification (400 fold) of ACC synthase from wounded pink tomato pericarp by classical techniques including ammonium sulfate precipitation, ion exchange and phenyl sepharose chromatography. Further purification results in a decrease in specific activity apparently due to the instability of the enzyme and the low levels present in plant tissue. Radiolabeling of a pyridoxal phosphate-utilizing protein in the ACC synthase enriched fraction was achieved. Evidence that this radiolabeled protein is ACC synthase will be presented. Amino acid sequence ...
We investigated the effect of irradiation on the kinetic characteristics of amino acid and glucose transport, and the effect on the activity of the cell membrane-bound enzyme 5'-nucleotidase and on the receptor-mediated stimulation of cyclic adenosine monophosphate synthesis by prostaglandin E1. Irradiation inhibited the sodium-dependent amino acid transport by a reduced binding of the amino acid to the transport unit. The transport of glucose, which appeared to be a sodium-independent process, was temporarily stimulated by increased maximal velocity of the transport. No effect was found on the binding to the transport unit. Irradiation increased the 5'-nucleotidase activity and decreased the prostaglandin E1-stimulated cyclic adenosine monophosphate synthesis 48 h after exposure to 20 Gy. It is concluded that irradiation decreases sodium-dependent transport by impairment of the transport unit, does not impair a sodium-independent process, and has ...
Four proteins from NCBI cog1816, previously annotated as adenosine deaminases, have been subjected to structural and functional characterization. Pa0148 (Pseudomonas aeruginosa PAO1), AAur1117 (Arthrobacter aurescens TC1), Sgx9403e, and Sgx9403g have been purified and their substrate profiles determined. Adenosine is not a substrate for any of these enzymes. All of these proteins will deaminate adenine to produce hypoxanthine with k(cat)/K(m) values that exceed 10(5) M(-1) s(-1). These enzymes will also accept 6-chloropurine, 6-methoxypurine, N-6-methyladenine, and 2,6-diaminopurine as alternate substrates. X-ray structures of Pa0148 and AAur1117 have been determined and reveal nearly identical distorted (?/?)(8) barrels with a single zinc ion that is characteristic of members of the amidohydrolase superfamily. Structures of Pa0148 with adenine, 6-chloropurine, and hypoxanthine were also determined, thereby permitting identification of the ...
Coutinho MF, Encarnao M, Gomes R, da Silva Santos L, Martins S, Sirois-Gagnon D, Bargal R, Filocamo M, Raas-Rothschild A, Tappino B, Laprise C, Cury GK, Schwartz IV, Artigals O, Prata MJ, Alves S. Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity. Mucolipidosis II (ML II alpha/beta), or I-cell disease, is a rare genetic disease in which activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent. GlcNAc-phosphotransferase is a multimeric enzyme encoded by two genes, GNPTAB and GNPTG. A spectrum of mutations in GNPTAB has been recently reported to cause ML II alpha/beta. Most of these mutations were found to be private or rare. ...
The authors studied the resolution of racemic glycidol through esterification with butyric acid catalyzed by porcine pancreatic lipase in organic media. A screening of seven solvents (log P values between 0.49 and 3.0, P being the n-octanol-water partition coefficient of the solvent) showed that neither log P nor the logarithm of the molar solubility of water in the solvent provides good correlations between enantioselectivity and the properties of the organic media. Chloroform was one of the best solvents as regards the enantiometic purity (e.p.) of the ester produced. In this solvent, the optimum temperature for the reaction was determined to be 35C. The enzyme exhibited maximum activity at a water content of 13 [plus minus] 2% (w/w). The enantiomeric purity obtained was 83 [plus minus] 2% of (S)-glycidol butyrate and did not depend on the alcohol concentration or the enzyme water content for values of these parameters up to 200 mM and 25% ...
Ionic liquids can enhance the activity, selectivity, and stability of enzyme catalysts. Enzymes and ionic liquids as catalysts are seen as a more environmentally friendly technology than the use of traditional catalyst materials in biofuels production. This study investigated the lipase catalyzed esterification reaction for biodiesel production in the presence of the ionic liquid BMIM PF{sub 6}. Methyl acetate was used as the acyl acceptor. A titremetric assay was conducted to measure the activity of the lipase with various amounts of ionic liquid. Reaction parameters were investigated in order to determine their effects on biodiesel conversion. An 80 per cent overall methyl oleate biodiesel yield was successfully produced in the presence of the ionic liquid. The ionic liquid improved lipase activity as well as overall biodiesel yield. Results also showed that the addition of the ionic liquid facilitated the separation of methyl esters from ...
2,6-Dinitrotoluene (2,6-DNT) and pentachlorophenol (PCP) are used for industrial purposes and are found in the environment as hazardous contaminants. Because concurrent exposure to both compounds can occur, it is of interest to determine if organochlorine compounds potentiate the effect of nitroaromatic chemicals. A significant increase in mutagenicity was observed in urines from mice treated with 2,6-DNT alone and in combination with PCP. By week 4, mice that received both 2,6-DNT and PCP excreted urine that was more mutagenic than that from animals which received only 2,6-DNT. At weeks 2 and 4, mice were sacrificed and intestinal enzyme activities (nitroreductase, azo reductase, {beta}-glucuronidase, dechlorinase, and dehydrochlorinase) were quantitated. The enhanced genotoxicity observed in urines from 2,6-DNT/PCP-treated mice coincided with a decrease in nitroreductase and an increase in {beta}-glucuronidase activities in the small intestine.
Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first enzyme in the biosynthetic pathway of the branched-chain amino acids. It catalyzes the conversion of two molecules of pyruvate into 2-acetolactate or one molecule of pyruvate and one molecule of 2-ketobutyrate into 2-aceto-2-hydroxybutyrate. AHAS requires the cofactors thiamine diphosphate (ThDP), Mg{sup 2+} and FAD for activity. The herbicides that target this enzyme are effective in protecting a broad range of crops from weed species. However, resistance in the field is now a serious problem worldwide. To address this, two new sulfonylureas, monosulfuron and monosulfuron ester, have been developed as commercial herbicides in China. These molecules differ from the traditional sulfonylureas in that the heterocyclic ring attached to the nitrogen atom of the sulfonylurea bridge is monosubstituted rather than disubstituted. The structures of these compounds in complex with the catalytic ...
The present study investigated the effects of peppermint (Mentha piperita), dill (Anethum graveolens) and basil (Ocimum basilicum) on yogurt formation, proteolysis and inhibition of angiotensin-1 converting enzyme (ACE). Herbal-yogurts had faster rates of pH reduction than plain-yogurt. All herbal-yogurts had higher (p < 0.05) antioxidant activities than plain-yogurt, both at the end of fermentation and throughout the storage period. The o-phthalaldehyde (OPA) peptides in herbal-yogurts increased by 28-36% after 7 days of storage. All herbal-yogurts showed higher anti-ACE activity than plain-yogurt at corresponding storage periods. M. piperita yogurt had highest inhibitory effect on ACE activity throughout the storage period. Peppermint, dill and basil may be used to modify microbial ferme...
Several enzymes of the metabolic pathways responsible for metabolism of cytosolic ribonucleotides and deoxyribonucleotides are located in mitochondria. Studies described in this paper suggest dysfunction of the mitochondria to affect these metabolic pathways and limit the available levels of cytosolic ribonucleotides and deoxyribonucleotides, which in turn can result in aberrant RNA and DNA synthesis. Mitochondrial dysfunction has been linked to genomic instability, and it is possible that the limiting effect of mitochondrial dysfunction on the levels of nucleotides and resulting aberrant RNA and DNA synthesis in part can be responsible for this link. This paper summarizes the parts of the metabolic pathways responsible for nucleotide metabolism that can be affected by mitochondrial dysfunction.
Our major goal of our work has been to develop and use NMR techniques to study how methanogenic archaebacteria deal with osmotic stress with the hope of providing insights into increasing the salt tolerance of other cells. The project has three main sections: (i) in vivo studies of methanogens; (ii) use of {sup l3}C- and {sup l5}N- labeled potential precursors and in vitro analyses of specific label uptake for elucidation of osmolyte dynamics and biosynthetic pathways of osmolytes in these organisms, and isolation of key biosynthetic enzymes; and (iii) collaborative studies on identification of organic solutes in other methanogens.
Our major goal of our work has been to develop and use NMR techniques to study how methanogenic archaebacteria deal with osmotic stress with the hope of providing insights into increasing the salt tolerance of other cells. The project has three main sections: (i) in vivo studies of methanogens; (ii) use of [sup l3]C- and [sup l5]N- labeled potential precursors and in vitro analyses of specific label uptake for elucidation of osmolyte dynamics and biosynthetic pathways of osmolytes in these organisms, and isolation of key biosynthetic enzymes; and (iii) collaborative studies on identification of organic solutes in other methanogens.
In an effort to improve the extrapolation of laboratory data to man and estimate risk of human reproductive toxicity associated with environmental exposure, the pharmacokinetic parameters of the testicular compartment are being studied. Of particular interest is the variety of enzyme systems capable of activating and detoxicating environmental chemicals and drugs. This report compares the metabolism of benzo(a)pyrene by the isolated perfused testis and testicular homogenates in vitro. The cell free in vitro system metabolized benzo(a)pyrene at a much greater rate than the perfused testis and produced a different spectrum of metabolites. Reliable laboratory prediction of biotransformation by the whole organ or intact animal is an essential aspect of reproductive toxicology.
The in vivo toxic effects of hexavalent chromium (20 mg/liter) on hemolymph glucose, tissue glycogen, total free sugars, and active and total phosphorylases of an edible, freshwater crab Barytelphusa guerini were studied. In a 15-day exposure span followed by a 15-day postexposure recovery, the time-course alterations in these constituent segments of the glycogen metabolism indicate an inconsistent depletion in metabolite levels and elevated enzyme activities during exposure period as well as hyperglycemia. An insignificant recovery was observed in these parameters on the 15th day of the postexposure phase.
The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were ...
A 60-year-old male was bitten by a venomous snake (Vipera ammodytes) and gradually developed signs of an allergic reaction including generalized itching, generalized rash, and chest discomfort. This was followed by severe retrosternal pain with electrocardiographic evidence of an inferior myocardial ischemia progressing to acute myocardial infarction. Cardiac enzymes and troponin, serum tryptase, and histamine were elevated. Coronary arteriography showed normal coronary arteries. This is a characteristic type I variant of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid reactions. This is the first report to show that viper bite...
The analgesic, dipyrone (1,phenyl-2,3-dimethyl-5-pyrazolone-4-methylamino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single-strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma-radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase-a cell membrane associated enzyme. (author). 18 refs., 6 figures.
The analgesic, dipyrone (1,phenyl-2,3-dimethyl-5-pyrazolone-4-methylamino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single-strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma-radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase-a cell membrane associated enzyme. (author).
The review covers the development within the field of cleavable surfactants since 2003. Cleavable surfactants are amphiphiles in which a weak linkage has been deliberately inserted, normally, but not always, between the hydrophobic tail and the polar headgroup. Alkali labile linkages that have been used for the purpose include normal ester bonds, betaine esters, and carbonates. Ketals and ortho esters are example of bonds that are susceptible to acid hydrolysis. Several investigations deal with cationic ester-containing surfactants, both monomeric and dimeric species, the latter being gemini surfactants. Ester, amide and carbonate containing surfactants have been investigated with respect to enzyme catalyzed hydrolysis. The main incentive for the development of novel cleavable surfactants ...
The crystal and molecular structures of the anti-acquired immunodeficiency syndrome agent 3'-azido-3'-deoxythymidine (AZT) have been determined by x-ray diffraction. There are two crystallographically independent AZT molecules in the crystal asymmetric unit; they have similar conformation and differ primarily in the glycosyl torsion angle. Comparisons with a hydrated thymidylate structure indicate that the azido group does not significantly affect the gross conformational preference of the molecule. The comparisons also suggest possible functional roles for the azido group in enzyme binding.
Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 ...
Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a #lambda#gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu"1"6"0#->#His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a #lambda#_m_a_x at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 ...
Prostaglandin E2 (PGE2) has been shown to increase the synthesis of hyaluronic acid in cultured fibroblasts by increasing the activity of hyaluronate synthetase, a group of plasma membrane-bound synthetic enzymes. We examined whether PGE2 also increased the activity of those enzyme systems involved in the synthesis of sulfated glycosaminoglycan in the human embryonic lung fibroblast. Exposure of cells to PGE2 resulted in dose-dependent increases in glucosamine incorporation into all sulfated glycosaminoglycan subtypes. PGE2 at 10(-7) mol/L increased total glycosaminoglycan per dish to 21.6 +/- 3.1 micrograms versus 12.0 +/- 2.5 micrograms in control untreated cultures. Stimulation of endogenous PGE2 production by bradykinin had a similar effect on glycosaminoglycan synthesis. To examine whether PGE2 affected sulfated glycosaminoglycan protein core production, cells were labeled with tritiated glucosamine in the presence of cycloheximide. Under ...
The thermostable Thermus aquaticus DNA polymerase (Taq Pol) has been the key factor in transforming the initial PCR method into one with huge impact in molecular biology and biotechnology. Therefore, the development of effective affinity adsorbents for the purification of Taq Pol, as well as other DNA polymerases, attracts the attention of the enzyme manufacturers and the research laboratories. In this report we describe a simple protocol for the purification of Taq Pol from E. coli lysates, leading to enzymes of high specific activity and purity. The protocol is based on a single affinity chromatography step, featuring an immobilized ligand selected from a structure-biased combinatorial library of dNTP-mimetic synthetic ligands. The ligand library was screened for its ability to bind and purify Taq Pol from E. coli lysates. One immobilized ligand (mABSGu) of the general formula X-Trz-Y, bearing 9-aminoethylguanine (AEGu) and aniline-2-sulfonic ...
Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased ...
The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by /sup 13/C-AP breath ...
The affinity label 8-((4-bromo-2,3-dioxobutyl)thio)adenosine 5{prime}-triphosphate (8-BDB-TA-5{prime}-TP) reacts covalently with rabbit muscle pyruvate kinase, incorporating 2 mol of reagent/mol of enzyme subunit upon complete inactivation. Protection against inactivation is provided by phosphoenolpyruvate, K{sup +}, and Mn{sup 2+} and only 1 mol of reagent/mol of subunit is incorporated. The authors have now identified the resultant modified residues. After reaction with 8-BDB-TA-5{prime}-TP at pH 7.0, modified enzyme was incubated with ({sup 3}H)NaBH{sub 4} to reduce the carbonyl groups of enzyme-bound 8-BDB-TA-5{prime}-TP and to introduce a radioactive tracer into the modified residues. Following carboxymethylation and digestion with trypsin, the radioactive peptides were separated on a phenylboronate agarose column followed by reverse-phase high-performance liquid chromatography in 0.1% trifluoroacetic acid with an ...
This study aimed to correlate the efficiency of enzymatic hydrolysis of the cellulose contained in a sugarcane bagasse sample pretreated with dilute H(2)SO(4) with the levels of independent variables such as initial content of solids and loadings of enzymes and surfactant (Tween 20), for two cellulolytic commercial preparations. The preparations, designated cellulase I and cellulase II, were characterized regarding the activities of total cellulases, endoglucanase, cellobiohydrolase, cellobiase, ?-glucosidase, xylanase, and phenoloxidases (laccase, manganese and lignin peroxidases), as well as protein contents. Both extracts showed complete cellulolytic complexes and considerable activities of xylanases, without activities of phenoloxidases. For the enzymatic hydrolyses, two 2(3) central composite full factorial designs were employed to evaluate the effects caused by the initial content of solids (1.19-4.81%, w/w) and loadings of enzymes ...
The effect of phosphonate anion (PHOS) on the corrosion of ordinary steel in simulated cooling water has been studied using weight loss, polarization curves and electrochemical impedance spectroscopy measurements. PHOS was studied in the concentration range from 7.5x10^-^5 to 10^-^3M. The results obtained reveal that PHOS perform excellently as corrosion inhibitor for ordinary steel in simulated cooling water. The inhibition efficiency of PHOS was increased with increasing both its concentration and water circulation velocity. These two factors seem to promote the adsorption of phosphorus and oxygen ions on the metal surface, leading to the formation of a protective layer with a greater charge transfer resistance and lower permeability. The inhibition efficiency decreased slightly with tem...
Purpose PR-104, a bioreductive prodrug in clinical trial, is a phosphate ester which is rapidly metabolized to the corresponding alcohol PR-104A. This dinitrobenzamide mustard is activated by reduction to hydroxylamine (PR-104H) and amine (PR-104M) metabolites selectively in hypoxic cells, and also independently of hypoxia by aldo-keto reductase (AKR) 1C3 in some tumors. Here, we evaluate reductive metabolism of PR-104A in mice and its significance for host toxicity. Methods The pharmacokinetics of PR-104, PR-104A and its reduced metabolites were investigated in plasma and tissues of mice (with and without SiHa or H460 tumor xenografts) and effects of potential oxidoreductase inhibitors were evaluated. Results Pharmacokinetic studies identified extensive non-tumor reduction of PR-104A to t...
Abstract Development of inhibitors and vaccines that mitigate rumen-derived methane by targeting methanogens relies on knowledge of the methanogens present. We investigated the composition of archaeal communities in the rumens of farmed sheep (Ovis aries), cattle (Bos taurus) and red deer (Cervus elaphus) using denaturing gradient gel electrophoresis (DGGE) to generate fingerprints of archaeal 16S rRNA genes. The total archaeal communities were relatively constant across species and diets, and were less variable and less diverse than bacterial communities. There were diet- and ruminant-species-based differences in archaeal community structure, but the same dominant archaea were present in all rumens. These were members of three coherent clades: species related to Methanobrevibacter ruminan...
Corrosion tests of titanium alloys VTI-0, OT4, VT5-1 and steel Kh18N1OT in 10% and 18% HCl with additions of carnallite at 40 deg C have been carried out. It has been established that titanium alloys in 10% and 18% HCl containing 5 and 10% carnallite are sufficiently corrosion resistant in the presence of 0.1-1% FeCl or HNO_3 and can be used for manufacturing the equipment of recirculation gas scrubbers. Steel Kh18N10T is unstable in all the media tested. It is subjected to intensive pitting. Specimens of steel Kh18N10T have also revealed edge cracking.
Diethylene glycol (DEG) is an industrial chemical, the misuse of which has led to numerous epidemic poisonings worldwide. The mechanism of its toxicity has not been defined as to the precise relationship between the metabolism of DEG and target organ toxicity. The purpose of this study was to investigate the mechanism for the acute toxicity of DEG, and the effect of the alcohol dehydrogenase inhibitor 4-methylpyrazole (fomepizole), by determining the relationship between accumulation of DEG or its metabolites and the resulting kidney and liver toxicity. Rats were treated by oral gavage with water, 2 g/kg DEG (low dose), 10 g/kg DEG (high dose), or 10 g/kg DEG + fomepizole, and blood and urine were collected over 48 h. Rats treated with high-dose DEG had metabolic acidosis, increased BUN an...
The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test t...
Astrocytes have important immune functions in CNS, and astrocytes stimulated by interferon-g were showed to have direct antimicrobial function. However whether astrocytes without the stimulation of cytokines have antibacterial function, and how this function is regulated are still largely unknown. In this study, we found that primary cultured astrocytes inhibited the growth of both gram-negative and gram-positive bacteria. Further more, we showed that interleukin-1b (IL-1b) enhanced the antibacterial effect in a dose-dependent manner, and the antibacterial effect of astrocytes from IL-1b receptor-deficient mice failed to be enhanced by IL-1b. IL-1b stimulated IkBa degradation, NF-kB nuclear translocation, and transactivation in astrocytes. NF-kB inhibitors blocked NF-kB activation and the ...
Abstract Background: Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods: A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results: This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician's Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug R...
This new book presents a practical how to approach to understanding and solving the problems of corrosion of structural materials. Although it is written mainly for those having a limited technical background in corrosion, it also provides more experienced engineers with a useful overview of the principles of corrosion and can be used as a general guide for developing a corrosion-control program. Contents include: the effects and economic impact of corrosion; basic concepts important to corrosion; principles of aqueous corrosion; forms of corrosion: recognition and prevention; types of corrosive environments; corrosion characteristics of structural materials; corrosion control by proper design; corrosion control by materials selection; corrosion control by protective coatings and inhibitors; corrosion control by cathodic and anodic protection; corrosion testing and monitoring; techniques for diagnosis of corrosion failures; and glossary of corrosion-related terms.
Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the ?-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antag...
Alkanol-amine is used for removing hydrogen sulfide and carbon dioxide from the gas stream. Contaminated amine is the amine which is contaminated by hydrocarbon, organic acid or iron sulfide, etc.. In addition, in the case when an antifoaming agent is excessively added to it or when it is decomposed chemically or thermally, it is considered that it is contaminated. When an amine solution becomes contaminated, several problems concerning operation control occur which would influence the effect of the amine treatment in consequence. By using activated charcoal, it is possible to decrease the additional amount of the antifoaming agent or corrosion inhibitor. This is because activated charcoal removes the decomposed product which causes the foaming phenomenon. In order to derive economical profit sufficiently, an activated charcoal system properly designed is necessary. In this article, the CALGON CLEANAMINE SYSTEM of Calgon Co. is introduced which restores the effect ...
Air flow rates and carbon dioxide concentrations of air entering and exiting eight H-Area waste tanks were monitored for a period of one year. The average instanteous concentration of carbon dioxide in air is within the range reported offsite, and therefore is not affect by operation of the coal-fired power plant adjacent to the tank farm. Waste solutions in each of the tanks were observed to be continuously absorbing carbon dioxide. The rate of absorption of carbon dioxide decreased linearly with the pH of the solution. Personnel exposure associated with the routine sampling and analysis of radioactive wastes stored at SRP to determine the levels of corrosion inhibitors in solution could be reduced by monitoring the absorption of carbon dioxide and using the relationship between pH and carbon dioxide absorption to determine the free hydroxide concentration in solution.
Summary Background Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease. Patients and Methods Seventeen chemo-na?ve UC patients with adequate performance status and organ function were treated with sorafenib 400?mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3?months), time to progression, median and 1?yr survival and ...
Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.