Phenolic profile and antioxidant activity from non-toxic Mexican Jatropha curcas L. shell methanolic extracts.

Science.gov (United States)

Perea-Domínguez, Xiomara Patricia; Espinosa-Alonso, Laura Gabriela; Hosseinian, Farah; HadiNezhad, Mehri; Valdez-Morales, Maribel; Medina-Godoy, Sergio

2017-03-01

Jatropha curcas seed shells are the by-product obtained during oil extraction process. Recently, its chemical composition has gained attention since its potential applications. The aim of this study was to identify phenolic compounds profile from a non-toxic J. curcas shell from Mexico, besides, evaluate J. curcas shell methanolic extract (JcSME) antioxidant activity. Free, conjugate and bound phenolics were fractionated and quantified (606.7, 193.32 and 909.59 μg/g shell, respectively) and 13 individual phenolic compounds were detected by HPLC. The radical-scavenging activity of JcSME was similar to Trolox and ascorbic acid by DPPH assay while by ABTS assay it was similar to BHT. Effective antioxidant capacity by ORAC was found (426.44 ± 53.39 μmol Trolox equivalents/g shell). The Mexican non-toxic J. curcas shell is rich in phenolic compounds with high antioxidant activity; hence, it could be considerate as a good source of natural antioxidants.

Fact Sheets: Air Toxics Rules for the Manufacture of Amino/Phenolic Resins

Science.gov (United States)

This page contains a December 1999 fact sheet for the proposed National Emission Standards for Hazardous Air Pollutants (NESHAP): Manufacture of Amino/Phenolic Resins and a September 2014 fact sheet with information regarding the final NESHAP

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

International Nuclear Information System (INIS)

Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Ding, Wen-Xing; Jaeschke, Hartmut

2015-01-01

3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M. [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Ding, Wen-Xing [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

2015-12-01

3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

Calix[4]arene-Based Enantioselective Fluorescent Sensors for the Recognition of N-Acetyl-aspartate

Institute of Scientific and Technical Information of China (English)

QING Guang-Yan; CHEN Zhi-Hong; WANG Feng; YANG Xi; MENG Ling-Zhi; HE Yong-Bing

2008-01-01

Two-armed chiral anion receptors (1 and 2), calix[4]arenes bearing dansyl fluorophore and (1R,2R)- or(1S,2S)-1,2-diphenylethylenediamine binding sites, were prepared and examined for their chiral amino acid anion binding abilities by the fluorescence spectra in dimethylsulfoxide (DMSO). The results of non-linear curve fitting indicate that 1 or 2 forms a 1 : 1 stoichiometry complex with N-acetyl-L-or D-aspartate by multiple hydrogen bonding interactions, exhibiting good enantioselective fluorescent recognition for the enantiomers of N-acetyl-as-partate, [receptor 1: Kass(D)/Kass(L)=6.74; receptor 2: Kass(L)/Kass(D)=6.48]. The clear fluorescent response difference indicates that receptors 1 and 2 could be used as a fluorescent chemosensor for N-Acetyl-aspartate.

Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

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Seung-Il Oh

2015-05-01

Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

Characterisation of a novel homodimeric N-acetyl-β-D-glucosaminidase from Streptococcus gordonii

International Nuclear Information System (INIS)

Harty, Derek W.S.; Chen Yingjian; Simpson, Christine L.; Berg, Tracey; Cook, Simon L.; Mayo, John A.; Hunter, Neil; Jacques, Nicholas A.

2004-01-01

An N-acetyl-β-D-glucosaminidase (GcnA) from Streptococcus gordonii FSS2 was cloned and sequenced. GcnA had a deduced molecular mass of 72,120 Da. The molecular weight after gel-filtration chromatography was 140,000 Da and by SDS-PAGE was 70,000 Da, indicating that the native protein was a homodimer. The deduced amino acid sequence had significant homology to a glycosyl hydrolase from Streptococcus pneumoniae and the conserved catalytic domain of the Family 20 glycosyl hydrolases. GcnA catalysed the hydrolysis of the synthetic substrates, 4-methylumbelliferyl (4MU)-N-acetyl-β-D-glucosaminide, 4MU-N-acetyl-β-D-galactosaminide, 4-MU-β-D-N,N ' -diacetylchitobioside, and 4-MU-β-D-N,N ' ,N''-chitotrioside as well as the respective chito-oligosaccharides. GcnA was optimally active at pH 6.6 and 42 deg. C. The K m for 4-MU-β-D-N,N ' ,N''-chitotrioside, 45 μM, was the lowest for all the substrates tested. Hg 2+ , Cu 2+ , Fe 2+ , and Zn 2+ completely inhibited while Co 2+ , Mn 2+ , and Ni 2+ partially inhibited activity. S. gordonii FSS2 and a GcnA negative mutant grew equally well on chito-oligosaccharides as substrates. The S. gordonii sequencing projects indicate two further N-acetyl-β-D-glucosaminidase activities

Binding of the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs to tRNA(phe..

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Anirban Basu

Full Text Available BACKGROUND: Three new analogs of berberine with aryl/ arylalkyl amino carbonyl methyl substituent at the 9-position of the isoquinoline chromophore along with berberrubine were studied for their binding to tRNA(phe by wide variety of biophysical techniques like spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting, viscosity and isothermal titration calorimetry. METHODOLOGY/ PRINCIPAL FINDINGS: Scatchard binding isotherms revealed that the cooperative binding mode of berberine was propagated in the analogs also. Thermal melting studies showed that all the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs stabilized the tRNA(phe more in comparison to berberine. Circular dichroism studies showed that these analogs perturbed the structure of tRNA(phe more in comparison to berberine. Ferrocyanide quenching studies and viscosity results proved the intercalative binding mode of these analogs into the helical organization of tRNA(phe. The binding was entropy driven for the analogs in sharp contrast to the enthalpy driven binding of berberine. The introduction of the aryl/arylalkyl amino carbonyl methyl substituent at the 9-position thus switched the enthalpy driven binding of berberine to entropy dominated binding. Salt and temperature dependent calorimetric studies established the involvement of multiple weak noncovalent interactions in the binding process. CONCLUSIONS/ SIGNIFICANCE: The results showed that 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs exhibited almost ten folds higher binding affinity to tRNA(phe compared to berberine whereas the binding of berberrubine was dramatically reduced by about twenty fold in comparison to berberine. The spacer length of the substitution at the 9-position of the isoquinoline chromophore appears to be critical in modulating the binding affinities towards tRNA(phe.

Purification, properties, and N-terminal amino acid sequence of homogeneous Escherichia coli 2-amino-3-ketobutyrate CoA ligase, a pyridoxal phosphate-dependent enzyme.

Science.gov (United States)

Mukherjee, J J; Dekker, E E

1987-10-25

Starting with 100 g (wet weight) of a mutant of Escherichia coli K-12 forced to grow on L-threonine as sole carbon source, we developed a 6-step procedure that provides 30-40 mg of homogeneous 2-amino-3-ketobutyrate CoA ligase (also called aminoacetone synthetase or synthase). This ligase, which catalyzes the cleavage/condensation reaction between 2-amino-3-ketobutyrate (the presumed product of the L-threonine dehydrogenase-catalyzed reaction) and glycine + acetyl-CoA, has an apparent molecular weight approximately equal to 85,000 and consists of two identical (or nearly identical) subunits with Mr = 42,000. Computer analysis of amino acid composition data, which gives the best fit nearest integer ratio for each residue, indicates a total of 387 amino acids/subunit with a calculated Mr = 42,093. Stepwise Edman degradation provided the N-terminal sequence of the first 21 amino acids. It is a pyridoxal phosphate-dependent enzyme since (a) several carbonyl reagents caused greater than 90% loss of activity, (b) dialysis against buffer containing hydroxylamine resulted in 89% loss of activity coincident with an 86% decrease in absorptivity at 428 nm, (c) incubation of the apoenzyme with 20 microM pyridoxal phosphate showed a parallel recovery (greater than 90%) of activity and 428-nm absorptivity, and (d) reduction of the holoenzyme with NaBH4 resulted in complete inactivation, disappearance of a new absorption maximum at 333 nm. Strict specificity for glycine is shown but acetyl-CoA (100%), n-propionyl-CoA (127%), or n-butyryl-CoA (16%) is utilized in the condensation reaction. Apparent Km values for acetyl-CoA, n-propionyl-CoA, and glycine are 59 microM, 80 microM, and 12 mM, respectively; the pH optimum = 7.5. Added divalent metal ions or sulfhydryl compounds inhibited catalysis of the condensation reaction.

Identification and quantification of N alpha-acetylated Y. pestis fusion protein F1-V expressed in Escherichia coli using LCMS E.

Science.gov (United States)

Bariola, Pauline A; Russell, Brett A; Monahan, Steven J; Stroop, Steven D

2007-05-31

N-terminal acetylation in E coli is a rare event catalyzed by three known N-acetyl-transferases (NATs), each having a specific ribosomal protein substrate. Multiple, gram-scale lots of recombinant F1-V, a fusion protein constructed from Y. Pestis antigens, were expressed and purified from a single stably transformed E. coli cell bank. A variant form of F1-V with mass increased by 42-43 Da was detected in all purified lots by electrospray orthogonal acceleration time-of-flight mass spectrometry (MS). Peptide mapping LCMS localized the increased mass to an N-terminal Lys-C peptide, residues 1-24, and defined it as +42.0308+/-0.0231 Da using a LockSpray exact mass feature and a leucine enkaphalin mass standard. Sequencing of the variant 1-24 peptide by LCMS and high-energy collision induced dissociation (LCMS(E)) further localized the modification to the amino terminal tri-peptide ADL and identified the modification as N(alpha)-acetylation. The average content of N(alpha)-acetylated F1-V in five lots was 24.7+/-2.6% indicating that a stable acetylation activity for F1-V was established in the E. coli expression system. Alignment of the F1-V N-terminal sequence with those of other known N(alpha)-acetylated ectopic proteins expressed in E. coli reveals a substrate motif analogous to the eukaryote NatA' acetylation pathway and distinct from endogenous E. coli NAT substrates.

N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells.

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Ramesh B Badisa

Full Text Available Cocaine has a short half-life of only about an hour but its effects, predominantly on the central nervous system (CNS, are fairly long-lasting. Of all cells within the CNS, astrocytes may be the first to display cocaine toxicity owing to their relative abundance in the brain. Cocaine entry could trigger several early response changes that adversely affect their survival, and inhibiting these changes could conversely increase their rate of survival. In order to identify these changes and the minimal concentrations of cocaine that can elicit them in vitro, rat C6 astroglia-like cells were treated with cocaine (2-4 mM for 1h and assayed for alterations in gross cell morphology, cytoplasmic vacuolation, viability, reactive oxygen species (ROS generation, glutathione (GSH levels, cell membrane integrity, F-actin cytoskeleton, and histone methylation. We report here that all of the above identified features are significantly altered by cocaine, and may collectively represent the key pathology underlying acute toxicity-mediated death of astroglia-like cells. Pretreatment of the cells with the clinically available antioxidant N-acetyl cysteine (NAC, 5 mM for 30 min inhibited these changes during subsequent application of cocaine and mitigated cocaine-induced toxicity. Despite repeated cocaine exposure, NAC pretreated cells remained highly viable and post NAC treatment also increased viability of cocaine treated cells to a smaller yet significant level. We show further that this alleviation by NAC is mediated through an increase in GSH levels in the cells. These findings, coupled with the fact that astrocytes maintain neuronal integrity, suggest that compounds which target and mitigate these early toxic changes in astrocytes could have a potentially broad therapeutic role in cocaine-induced CNS damage.

Amino acid analogs for tumor imaging

International Nuclear Information System (INIS)

Goodman, M.M.; Shoup, T.

1998-01-01

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [ 18 F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid

ZnAl2O4@SiO2 nanocomposite catalyst for the acetylation of alcohols, phenols and amines with acetic anhydride under solvent-free conditions

Institute of Scientific and Technical Information of China (English)

Saeed Farhadi; Kosar Jahanara

2014-01-01

A ZnAl2O4@SiO2 nanocomposite was prepared from metal nitrates and tetraethyl orthosilicate by the sol-gel process, and characterized by X-ray diffraction, Fourier transform infrared, transmission electron microscopy, and N2 adsorption-desorption measurements. The nanocomposite was tested as a heterogeneous catalyst for the acetylation of alcohols, phenols, and amines under solvent-free conditions. Under optimized conditions, efficient acetylation of these substrates with acetic anhy-dride over the ZnAl2O4@SiO2 nanocomposite was obtained. Acetylation of anilines and primary aliphatic amines proceeded rapidly at room temperature, while the reaction time was longer for the acetylation of alcohols and phenols, showing that an amine NH2 group can be selectively acetylated in the presence of alcoholic or phenolic OH groups. The catalyst can be reused without obvious loss of catalytic activity. The catalytic activity of the ZnAl2O4@SiO2 nanocomposite was higher than that of pure ZnAl2O4. The method gives high yields, and is clean, cost effective, compatible with sub-strates having other functional groups and it is suitable for practical organic synthesis.

Toxicity of Phenol and Salt on the Phenol-Degrading Pseudomonas aeruginosa Bacterium

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Samaei

2016-08-01

Full Text Available Background Phenolic compounds, phenol and phenol derivatives are environmental contaminants in some industrial effluents. Entrance of such substances into the environment causes severe environmental pollution, especially pollution of water resources. Biological treatment is a method that uses the potential of microorganisms to clean up contaminated environments. Among microorganisms, bacteria play an important role in treating wastewater contaminated with phenol. Objectives This study aimed to examine the effects of Pseudomonas aeruginosa on degradation of phenol in wastewater contaminated with this pollutant. Methods In this method, the growth rate of P. aeruginosa bacteria was investigated using different concentrations of salt and phenol. This is an experimental study conducted as a pilot in a batch reactor with different concentrations of phenol (25, 50, 100, 150, 300 and 600 mg L-1 and salt (0%, 0.5%, 1%, 2.5% and 5% during 9, 12 and 15 hours. During three days, from 5 experimental and 3 control samples, 18 samples were taken a day forming a sample size of 54 samples for each phenol concentration. Given the number of phenol concentrations (n = 6, a total of 324 samples were analyzed using a spectrophotometer at a wavelength of 600 nm. Results The phenol concentration of 600 mg L-1 was toxic for P. aeruginosa. However, at a certain concentration, it acts as a carbon source for P. aeruginosa. During investigations, it was found that increasing the concentration of phenol increases the rate of bacteria growth. The highest bacteria growth rate occurred was at the salt concentration of zero and phenol concentration of 600 mg L-1. Conclusions The findings of the current study indicate that at high concentrations of salt, the growth of bacteria reduces so that it stops at a concentration of 50 mg L-1 (5%. Thus, the bacterium is halotolerant or halophilic. With an increase in phenol concentration, the growth rate increased. Phenol toxicity appears

In-source formation of N-acetyl-p-benzoquinone imine (NAPQI), the putatively toxic acetaminophen (paracetamol) metabolite, after derivatization with pentafluorobenzyl bromide and GC-ECNICI-MS analysis.

Science.gov (United States)

Tsikas, Dimitrios; Trettin, Arne; Zörner, Alexander A; Gutzki, Frank-Mathias

2011-05-15

Pentafluorobenzyl (PFB) bromide (PFB-Br) is a versatile derivatization reagent for numerous classes of compounds. Under electron-capture negative-ion chemical ionization (ECNICI) conditions PFB derivatives of acidic compounds readily and abundantly ionize to produce intense anions due to [M-PFB](-). In the present article we investigated the PFB-Br derivatization of unlabelled acetaminophen (N-acetyl-p-aminophenol, NAPAP-d(0); paracetamol; MW 151) and tetradeuterated acetaminophen (NAPAP-d(4); MW 155) in anhydrous acetonitrile and their GC-ECNICI-MS behavior using methane as the buffer gas. In addition to the expected anions [M-PFB](-) at m/z 150 from NAPAP-d(0) and m/z 154 from NAPAP-d(4), we observed highly reproducibly almost equally intense anions at m/z 149 and m/z 153, respectively. Selected ion monitoring of these ions is suitable for specific and sensitive quantification of acetaminophen in human plasma and urine. Detailed investigations suggest in-source formation of N-acetyl-p-benzoquinone imine (NAPQI; MW 149), the putatively toxic acetaminophen metabolite, from the PFB ether derivative of NAPAP. GC-ECNICI-MS of non-derivatized NAPAP did not produce NAPQI. The peak area ratio of m/z 149 to m/z 150 and of m/z 153 to m/z 154 decreased with increasing ion-source temperature in the range 100-250°C. Most likely, NAPQI formed in the ion-source captures secondary electrons to become negatively charged (i.e., [NAPQI](-)) and thus detectable. Formation of NAPQI was not observed under electron ionization (EI) conditions, i.e., by GC-EI-MS, from derivatized and non-derivatized NAPAP. NAPQI was not detectable in flow injection analysis LC-MS of native NAPAP in positive electrospray ionization (ESI) mode, whereas in negative ESI mode low extent NAPQI formation was observed (<5%). Our results suggest that oxidation of drug derivatives in the ion-sources of mass spectrometers may form intermediates that are produced from activated drugs in enzyme-catalyzed reactions

N,O6-partially acetylated chitosan nanoparticles hydrophobically-modified for controlled release of steroids and vitamin E

DEFF Research Database (Denmark)

Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen

2013-01-01

Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also character......Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also...

Neurotoxic Non-proteinogenic Amino Acid β-N-Methylamino-L-alanine and Its Role in Biological Systems.

Science.gov (United States)

Popova, A A; Koksharova, O A

2016-08-01

Secondary metabolites of photoautotrophic organisms have attracted considerable interest in recent years. In particular, molecules of non-proteinogenic amino acids participating in various physiological processes and capable of producing adverse ecological effects have been actively investigated. For example, the non-proteinogenic amino acid β-N-methylamino-L-alanine (BMAA) is neurotoxic to animals including humans. It is known that BMAA accumulation via the food chain can lead to development of neurodegenerative diseases in humans such as Alzheimer's and Parkinson's diseases as well as amyotrophic lateral sclerosis. Moreover, BMAA can be mistakenly incorporated into a protein molecule instead of serine. Natural sources of BMAA and methods for its detection are discussed in this review, as well as the role of BMAA in metabolism of its producers and possible mechanisms of toxicity of this amino acid in different living organisms.

A rapid phenol toxicity test based on photosynthesis and movement of the freshwater flagellate, Euglena agilis Carter

International Nuclear Information System (INIS)

Kottuparambil, Sreejith; Kim, Youn-Jung; Choi, Hoon; Kim, Mi-Sung; Park, Areum; Park, Jihae; Shin, Woongghi; Han, Taejun

2014-01-01

Highlights: • Rapid phenol toxicity tests (1 h) were developed based on Chl a fluorescence and the movement parameters of Euglena agilis. • Phenol significantly reduced F v /F m of PS II and rETRmax with EC50 values of 8.94 and 4.67 mM, respectively. • Among the movement parameters tested, velocity was the most sensitive biomarker with an EC50 of 3.17 mM. • The EC50 values for F v /F m , motility, and velocity appear to overlap the environmental permissible levels of phenol. - Abstract: Phenol, a monosubstituted aromatic hydrocarbon with various commercial uses, is a major organic constituent in industrial wastewaters. The ecotoxic action of phenol for aquatic environment is well known. In this study, rapid phenol toxicity tests (1 h) were developed based on chlorophyll a (Chl a) fluorescence and the movement parameters of the freshwater flagellate, Euglena agilis Carter. Phenol significantly reduced the maximum quantum yield (F v /F m ) of photosystem II (PS II) and the maximum photosynthetic electron transport rate (rETR max ) with median effective concentration (EC 50 ) values of 8.94 and 4.67 mM, respectively. Phenol reduced the motility and triggered change in the swimming velocity of the test organism. Among the parameters tested, velocity was the most sensitive biomarker with an EC 50 of 3.17 mM. The EC 50 values for F v /F m , motility, and velocity appear to overlap the permitted levels of phenol. In conclusion, the photosynthesis and movement of E. agilis can be fast and sensitive risk assessment parameters for the evaluation of phenol toxicity in municipal and industrial effluents

Protective Roles of N-acetyl Cysteine and/or Taurine against Sumatriptan-Induced Hepatotoxicity

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Javad Khalili Fard

2016-12-01

Full Text Available Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening. Results: It was revealed that liver toxicity induced by sumatriptan in in freshly isolated parenchymal hepatocytes is dose-dependent. Sumatriptan caused significant free radical generation followed by lipid peroxide formation, mitochondrial injury as well as lysosomal damage. Moreover, sumatriptan reduced cellular glutathione content. Taurine and N-acetyl cysteine were able to protect hepatocytes against sumatriptan-induced harmful effects. Conclusion: It is concluded that sumatriptan causes oxidative stress in hepatocytes and the decreased hepatocytes glutathione has a key role in the sumatriptan-induced harmful effects. Also, N-acetyl cysteine and/or taurine could be used as treatments in sumatriptan-induced side effects.

Cadmium-induced oxidative damage and protective effects of N-acetyl-L-cysteine against cadmium toxicity in Solanum nigrum L

International Nuclear Information System (INIS)

Deng Xiaopeng; Xia Yan; Hu Wei; Zhang Hongxiao; Shen Zhenguo

2010-01-01

The effects of cadmium (Cd) on the accumulation of hydrogen peroxide (H 2 O 2 ) and antioxidant enzyme activities in roots of Solanum nigrum L. and the role of N-acetyl-L-cysteine (NAC) as a cysteine (Cys) donor against Cd toxicity were investigated. Cd at 50 and 200 μM significantly increased the contents of thiobarbituric acid-reactive substances (TBARS), the production of H 2 O 2 and superoxide anion (O 2 · - ), and the activities of catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione peroxidase (GSH-Px), glutathione reductase, and superoxide dismutase. Experiments with diphenylene iodonium as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and NaN 3 as an inhibitor of peroxidase showed that the major source of Cd-induced reactive oxygen species in the roots may include plasma membrane-bound NADPH oxidase and peroxidase. In addition, the effects of NAC on plant growth, antioxidant enzyme activity, and non-protein thiol content were analyzed. Under Cd stress, the addition of 500 μM NAC decreased the contents of TBARS and production of H 2 O 2 and O 2 · - , but increased levels of Cys and reduced glutathione (GSH), phytochelatins, and activity of GSH-Px in roots. These results suggest that NAC could protect plants from oxidative stress damage, and this protection seems to be performed via increased GSH biosynthesis. Furthermore, NAC treatment also increased the contents of protein thiols in S. nigrum roots. By using size-exclusion chromatography, we found involvement of NAC in the Cd tolerance mechanism through increased biosynthesis of Cd-binding proteins.

A rapid phenol toxicity test based on photosynthesis and movement of the freshwater flagellate, Euglena agilis Carter

Energy Technology Data Exchange (ETDEWEB)

Kottuparambil, Sreejith [Institute of Green Environmental Research Center, Incheon National University, Incheon 406 840 (Korea, Republic of); Kim, Youn-Jung [Institute of Green Environmental Research Center, Incheon National University, Incheon 406 840 (Korea, Republic of); Department of Marine Science, Incheon National University, Incheon 406 840 (Korea, Republic of); Green-Pioneer (Ltd.), Incheon National University, Incheon 406 840 (Korea, Republic of); Choi, Hoon; Kim, Mi-Sung; Park, Areum; Park, Jihae [Institute of Green Environmental Research Center, Incheon National University, Incheon 406 840 (Korea, Republic of); Shin, Woongghi [Department of Biology, Chungnam University, Daejeon 306 764 (Korea, Republic of); Han, Taejun, E-mail: hanalgae@hanmail.net [Institute of Green Environmental Research Center, Incheon National University, Incheon 406 840 (Korea, Republic of); Department of Marine Science, Incheon National University, Incheon 406 840 (Korea, Republic of); Green-Pioneer (Ltd.), Incheon National University, Incheon 406 840 (Korea, Republic of)

2014-10-15

Highlights: • Rapid phenol toxicity tests (1 h) were developed based on Chl a fluorescence and the movement parameters of Euglena agilis. • Phenol significantly reduced F{sub v}/F{sub m} of PS II and rETRmax with EC50 values of 8.94 and 4.67 mM, respectively. • Among the movement parameters tested, velocity was the most sensitive biomarker with an EC50 of 3.17 mM. • The EC50 values for F{sub v}/F{sub m}, motility, and velocity appear to overlap the environmental permissible levels of phenol. - Abstract: Phenol, a monosubstituted aromatic hydrocarbon with various commercial uses, is a major organic constituent in industrial wastewaters. The ecotoxic action of phenol for aquatic environment is well known. In this study, rapid phenol toxicity tests (1 h) were developed based on chlorophyll a (Chl a) fluorescence and the movement parameters of the freshwater flagellate, Euglena agilis Carter. Phenol significantly reduced the maximum quantum yield (F{sub v}/F{sub m}) of photosystem II (PS II) and the maximum photosynthetic electron transport rate (rETR{sub max}) with median effective concentration (EC{sub 50}) values of 8.94 and 4.67 mM, respectively. Phenol reduced the motility and triggered change in the swimming velocity of the test organism. Among the parameters tested, velocity was the most sensitive biomarker with an EC{sub 50} of 3.17 mM. The EC{sub 50} values for F{sub v}/F{sub m}, motility, and velocity appear to overlap the permitted levels of phenol. In conclusion, the photosynthesis and movement of E. agilis can be fast and sensitive risk assessment parameters for the evaluation of phenol toxicity in municipal and industrial effluents.

Arsenic Metabolites, Including N-Acetyl-4-hydroxy-m-arsanilic Acid, in Chicken Litter from a Roxarsone-Feeding Study Involving 1600 Chickens.

Science.gov (United States)

Yang, Zonglin; Peng, Hanyong; Lu, Xiufen; Liu, Qingqing; Huang, Rongfu; Hu, Bin; Kachanoski, Gary; Zuidhof, Martin J; Le, X Chris

2016-07-05

The poultry industry has used organoarsenicals, such as 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, ROX), to prevent disease and to promote growth. Although previous studies have analyzed arsenic species in chicken litter after composting or after application to agricultural lands, it is not clear what arsenic species were excreted by chickens before biotransformation of arsenic species during composting. We describe here the identification and quantitation of arsenic species in chicken litter repeatedly collected on days 14, 24, 28, 30, and 35 of a Roxarsone-feeding study involving 1600 chickens of two strains. High performance liquid chromatography separation with simultaneous detection by both inductively coupled plasma mass spectrometry and electrospray ionization tandem mass spectrometry provided complementary information necessary for the identification and quantitation of arsenic species. A new metabolite, N-acetyl-4-hydroxy-m-arsanilic acid (N-AHAA), was identified, and it accounted for 3-12% of total arsenic. Speciation analyses of litter samples collected from ROX-fed chickens on days 14, 24, 28, 30, and 35 showed the presence of N-AHAA, 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), inorganic arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), and ROX. 3-AHPAA accounted for 3-19% of the total arsenic. Inorganic arsenicals (the sum of As(III) and As(V)) comprised 2-6% (mean 3.5%) of total arsenic. Our results on the detection of inorganic arsenicals, methylarsenicals, 3-AHPAA, and N-AHAA in the chicken litter support recent findings that ROX is actually metabolized by the chicken or its gut microbiome. The presence of the toxic metabolites in chicken litter is environmentally relevant as chicken litter is commonly used as fertilizer.

Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

Beta-endorphin and alpha-n-acetyl beta-endorphin; synthesis, conformation and binding parameter

Energy Technology Data Exchange (ETDEWEB)

Lovegren, E.S.

1986-01-01

Beta-endorphin (EP) is a 31-residue opioid peptide found in many tissues, including the pituitary, brain and reproductive tract. Alpha-amino-acetyl beta-endorphin (AcEP) was characterized spectroscopically by proton nuclear magnetic resonance (NMR) and circular dichroism in deuterated water and trifluoroethanol (TFE). Both EP and AcEP bind to neuroblastoma N2a cells. This binding was not mediated through opiate receptors, and both peptides seemed to bind at common sites. Ovarian immunoreactive-EP levels were determined for immature and mature rates. These levels were found to be responsive to exogenous gonadotropin treatment in immature animals. A large percentage of the immunoreactive-EP is present in follicular fluid, and most of the endorphin-like peptides were acetylated, as measured by radioimmunoassay. Chromatogaphic analysis suggested at least three EP-like species: EP, a carboxy-terminally cleaved and an amino-terminally acetylated EP.

Prey-induced changes in the accumulation of amino acids and phenolic metabolites in the leaves of Drosera capensis L.

Science.gov (United States)

Kováčik, Jozef; Klejdus, Bořivoj; Stork, František; Hedbavny, Josef

2012-04-01

Effect of prey feeding (ants Formica fusca) on the quantitative changes in the accumulation of free amino acids, soluble proteins, phenolic metabolites and mineral nutrients in the leaves of carnivorous plant Drosera capensis was studied. Arginine was the most abundant compound in Drosera leaves, while proline was abundant in ants. The amount of the majority of amino acids and their sum were elevated in the fed leaves after 3 and 21 days, and the same, but with further enhancement after 21 days, was observed in ants. Accumulation of amino acids also increased in young non-fed leaves of fed plants. Soluble proteins decreased in ants, but were not enhanced in fed leaves. This confirms the effectiveness of sundew's enzymatic machinery in digestion of prey and suggests that amino acids are not in situ deposited, but rather are allocated within the plant. The content of total soluble phenols, flavonoids and two selected flavonols (quercetin and kaempferol) was not affected by feeding in Drosera leaves, indicating that their high basal level was sufficient for the plant's metabolism and prey-induced changes were mainly N based. The prey also showed to be an important source of other nutrients besides N, and a stimulation of root uptake of some mineral nutrients is assumed (Mg, Cu, Zn). Accumulation of Ca and Na was not affected by feeding.

Catalytic Ozonation of Phenolic Wastewater: Identification and Toxicity of Intermediates

Directory of Open Access Journals (Sweden)

Mahdi Farzadkia

2014-01-01

Full Text Available A new strategy in catalytic ozonation removal method for degradation and detoxification of phenol from industrial wastewater was investigated. Magnetic carbon nanocomposite, as a novel catalyst, was synthesized and then used in the catalytic ozonation process (COP and the effects of operational conditions such as initial pH, reaction time, and initial concentration of phenol on the degradation efficiency and the toxicity assay have been investigated. The results showed that the highest catalytic potential was achieved at optimal neutral pH and the removal efficiency of phenol and COD is 98.5% and 69.8%, respectively. First-order modeling demonstrated that the reactions were dependent on the initial concentration of phenol, with kinetic constants varying from 0.038 min−1  ([phenol]o = 1500 mg/L to 1.273 min−1 ([phenol]o = 50 mg/L. Bioassay analysis showed that phenol was highly toxic to Daphnia magna (LC50 96 h=5.6 mg/L. Comparison of toxicity units (TU of row wastewater (36.01 and the treated effluent showed that TU value, after slightly increasing in the first steps of ozonation for construction of more toxic intermediates, severely reduced at the end of reaction (2.23. Thus, COP was able to effectively remove the toxicity of intermediates which were formed during the chemical oxidation of phenolic wastewaters.

Cadmium-induced oxidative damage and protective effects of N-acetyl-L-cysteine against cadmium toxicity in Solanum nigrum L

Energy Technology Data Exchange (ETDEWEB)

Deng Xiaopeng; Xia Yan; Hu Wei [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China); Zhang Hongxiao, E-mail: hxzhang@njau.edu.cn [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China); Shen Zhenguo, E-mail: zgshen@njau.edu.cn [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China)

2010-08-15

The effects of cadmium (Cd) on the accumulation of hydrogen peroxide (H{sub 2}O{sub 2}) and antioxidant enzyme activities in roots of Solanum nigrum L. and the role of N-acetyl-L-cysteine (NAC) as a cysteine (Cys) donor against Cd toxicity were investigated. Cd at 50 and 200 {mu}M significantly increased the contents of thiobarbituric acid-reactive substances (TBARS), the production of H{sub 2}O{sub 2} and superoxide anion (O{sub 2}{center_dot}{sup -}), and the activities of catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione peroxidase (GSH-Px), glutathione reductase, and superoxide dismutase. Experiments with diphenylene iodonium as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and NaN{sub 3} as an inhibitor of peroxidase showed that the major source of Cd-induced reactive oxygen species in the roots may include plasma membrane-bound NADPH oxidase and peroxidase. In addition, the effects of NAC on plant growth, antioxidant enzyme activity, and non-protein thiol content were analyzed. Under Cd stress, the addition of 500 {mu}M NAC decreased the contents of TBARS and production of H{sub 2}O{sub 2} and O{sub 2}{center_dot}{sup -}, but increased levels of Cys and reduced glutathione (GSH), phytochelatins, and activity of GSH-Px in roots. These results suggest that NAC could protect plants from oxidative stress damage, and this protection seems to be performed via increased GSH biosynthesis. Furthermore, NAC treatment also increased the contents of protein thiols in S. nigrum roots. By using size-exclusion chromatography, we found involvement of NAC in the Cd tolerance mechanism through increased biosynthesis of Cd-binding proteins.

Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

Science.gov (United States)

Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

2005-04-01

The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

Bacterial removal of toxic phenols from an industrial effluent

African Journals Online (AJOL)

STORAGESEVER

2008-07-04

Jul 4, 2008 ... Chlorinated phenols, widely used in industries, are of growing concern owing to their high toxicity, .... phenol-degradation ability of bacterial isolate at the high phenol .... ed virtually no decrease in the respiratory response over.

Fluorinated analogs of malachite green: synthesis and toxicity.

Science.gov (United States)

Kraus, George A; Jeon, Insik; Nilsen-Hamilton, Marit; Awad, Ahmed M; Banerjee, Jayeeta; Parvin, Bahram

2008-04-27

A series of fluorinated analogs of malachite green (MG) have been synthesized and their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell line examined. The toxicity profiles were found to be different for these two species. Two analogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem to be the most promising analogs because they showed the lowest toxicity to the human cells.

Preclinical evaluation of neurotensin(8-13) analog radiolabeled with 99mTc: in vitro and in vivo characterization

International Nuclear Information System (INIS)

Teodoro, Rodrigo

2010-01-01

The radiolabeling of receptor specific biomolecules with 99m Tc using bifunctional chelator agents represents a growing field in Nuclear Medicine, specially, regarding regulatory peptides, such as Neurotensin, which are important in several essential physiological functions, particularly in tumor growth. The aim of the study was the comparative radiolabeling evaluation of the double-stabilized NT(8-13) analog with 99m Tc, via the bifunctional chelating agents 6- hydrazinonicotinamide (HYNIC) and S-acetyl-mercaptoacetyltriglycine (MAG3) in MDA-MB-231 breast cancer cell line. High radiochemical yields (> 97%) and stability toward transchelant agents was observed for both radiolabeled analogs. Also, comparable in vitro behaviour regarding the percentage of plasma protein binding (nearby 22%), metabolic stability, receptor binding affinity (nM range), and internalization/externalization rates were obtained. The greater lipophilicity found for the analog radiolabeled via MAG 3 , reflected in the major differences in biodistribution studies. The in vivo metabolic stability studies suggested that the degradation observed in the later time point (90 min) for the conjugate radiolabeled via HYNIC, leads not only to lower tumor uptake accumulation (0,44±0,02% ID/g), but also to lower tumor-to-non-tumor ratios ( 3 had been confirmed in the present study, a structural re-design aiming the reduction of the high gastrointestinal uptake must be done in order to guarantee the potential applicability of MAG 3 -radio complex. (author)

Copper(II) Binding Sites in N-Terminally Acetylated α-Synuclein: A Theoretical Rationalization.

Science.gov (United States)

Ramis, Rafael; Ortega-Castro, Joaquín; Vilanova, Bartolomé; Adrover, Miquel; Frau, Juan

2017-08-03

The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121. However, in the N-terminally acetylated protein, present in vivo, the Met1 site is blocked. In this work, we simplify the representation of the protein by modeling each experimentally found binding site as a complex between an N-terminally acetylated α-synuclein dipeptide (or several independent residues) and a Cu(II) cation, and compare the results with a number of additional, structurally analogous sites not experimentally found. This way of representing the binding sites, although extremely simple, allows us to reproduce experimental results and to provide a theoretical rationale to explain the preference of Cu(II) for certain sites, as well as explicit geometrical structures for the complexes formed. These results are important to understand the interactions between α-synuclein and Cu(II), one of the factors inducing structural changes in the protein and leading to aggregated forms of it which may play a role in neurodegeneration.

Cytotoxicity of Phenol Red in Toxicity Assays for Carbon Nanoparticles

Directory of Open Access Journals (Sweden)

Chunhai Fan

2012-09-01

Full Text Available To explore the novel properties of carbon nanoparticles (CNPs in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium by multi-walled carbon nanotubes (MWNTs and three kinds of carbon blacks (CBs with nanosize, and its effects on cytotoxicity were studied. Results indicated that the phenol red adsorbed and delivered into cells by CBs was responsible for the toxicity to Hela cells in the medium without serum. The cellular uptake of phenol red was verified using 125I-labeling techniques. The size-dependent cytotoxicity of CBs was found to closely correlate to adsorption of phenol red, cellular uptake of phenol red-CB complexes and the amount of phenol red delivered into the cells by CBs. Although the CBs were either nontoxic or slightly toxic, as vehicles of phenol red, they played an essential role in the cytotoxicity induced by phenol red. However, MWNTs showed an intrinsic cytotoxicity independent of phenol red. The implications associated with these findings are discussed.

NetAcet: prediction of N-terminal acetylation sites

DEFF Research Database (Denmark)

Kiemer, Lars; Bendtsen, Jannick Dyrløv; Blom, Nikolaj

2005-01-01

Summary: We present here a neural network based method for prediction of N-terminal acetylation-by far the most abundant post-translational modification in eukaryotes. The method was developed on a yeast dataset for N-acetyltransferase A (NatA) acetylation, which is the type of N-acetylation for ......Summary: We present here a neural network based method for prediction of N-terminal acetylation-by far the most abundant post-translational modification in eukaryotes. The method was developed on a yeast dataset for N-acetyltransferase A (NatA) acetylation, which is the type of N...

Subcritical water extraction of amino acids from Mars analog soils.

Science.gov (United States)

Noell, Aaron C; Fisher, Anita M; Fors-Francis, Kisa; Sherrit, Stewart

2018-01-18

For decades, the Martian regolith has stymied robotic mission efforts to catalog the organic molecules present. Perchlorate salts, found widely throughout Mars, are the main culprit as they breakdown and react with organics liberated from the regolith during pyrolysis, the primary extraction technique attempted to date on Mars. This work further develops subcritical water extraction (SCWE) as a technique for extraction of amino acids on future missions. The effect of SCWE temperature (185, 200, and 215°C) and duration of extraction (10-120 min) on the total amount and distribution of amino acids recovered was explored for three Mars analog soils (JSC Mars-1A simulant, an Atacama desert soil, and an Antarctic Dry Valleys soil) and bovine serum albumin (as a control solution of known amino acid content). Total amounts of amino acids extracted increased with both time and temperature; however, the distribution shifted notably due to the destruction of the amino acids with charged or polar side chains at the higher temperatures. The pure bovine serum albumin solution and JSC Mars 1A also showed lower yields than the Atacama and Antarctic extractions suggesting that SCWE may be less effective at hydrolyzing large or aggregated proteins. Changing solvent from water to a dilute (10 mM) HCl solution allowed total extraction efficiencies comparable to the higher temperature/time combinations while using the lowest temperature/time (185°C/20 min). The dilute HCl extractions also did not lead to the shift in amino acid distribution observed at the higher temperatures. Additionally, adding sodium perchlorate salt to the extraction did not interfere with recoveries. Native magnetite in the JSC Mars-1A may have been responsible for destruction of glycine, as evidenced by its uncharacteristic decrease as the temperature/time of extraction increased. This work shows that SCWE can extract high yields of native amino acids out of Mars analog soils with minimal disruption of the

Biosynthesis and release of beta-endorphin-, N-acetyl beta-endorphin-, beta-endorphin-(1-27)-, and N-acetyl beta-endorphin-(1-27)-like peptides by rat pituitary neurointermediate lobe: beta-endorphin is not further processed by anterior lobe

International Nuclear Information System (INIS)

Liotta, A.S.; Yamaguchi, H.; Krieger, D.T.

1981-01-01

Continuous labeling and pulse-chase techniques were employed to study the synthesis and secretion of multiple forms of immunoreactive beta-endorphin by cultured dispersed rat anterior lobe cells and intact neurointermediate pituitary lobe. Intact neurointermediate lobes incorporated radiolabeled amino acids into four to six forms of immunoreactive beta-endorphin. Four of these forms were physicochemically similar to authentic beta-endorphin, N-acetylated beta-endorphin, beta-endorphin-(1-27), and N-acetylated beta-endorphin-(1-27). Pulse-chase studies indicated that a beta-lipotropin-like molecule served as a metabolic intermediate for a beta-endorphin-like molecule. As beta-endorphin-like material accumulated in the cell, some of it was N-acetylated (approximately 18% at 2 hr chase and approximately 65% at 18 hr chase). At later chase times, beta-endorphin-(1-27)- and N-acetylated beta-endorphin-(1-27)-like peptides were the predominant molecular species detected. All endorphin forms were detected in unlabeled tissue maintained in culture or tissue continuously labeled for 72 hr and were released into the medium under basal, stimulatory (10(-8) M norepinephrine), or inhibitory (10(-7) M dopamine) incubation conditions. In all cases, beta-endorphin-(1-27)-like species were the predominant forms (more than 70% of total) present in the cells and released into the medium. In contrast, approximately 90% of radiolabeled immunoreactive beta-endorphin extracted from anterior lobe cells and medium similarly incubated appeared to represent the authentic beta-endorphin molecule. Continuous labeling (72 hr) revealed the beta-lipotropin/beta-endorphin molar ratio to be approximately 4. We conclude that, in anterior lobe, most of the beta-endorphin is not processed further and is released intact, while in neurointermediate lobe, it serves as a biosynthetic intermediate

Acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase. Evidence for a transmembrane acetylation mechanism

International Nuclear Information System (INIS)

Bame, K.J.; Rome, L.H.

1985-01-01

The lysosomal membrane enzyme acetyl-CoA: alpha-glucosaminide N-acetyltransferase catalyzes the transfer of an acetyl group from acetyl-CoA to terminal alpha-linked glucosamine residues of heparan sulfate. The reaction mechanism was examined using highly purified lysosomal membranes from rat liver. The reaction was followed by measuring the acetylation of a monosaccharide acetyl acceptor, glucosamine. The enzyme reaction was optimal above pH 5.5, and a 2-3-fold stimulation of activity was observed when the membranes were assayed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicated that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. Further evidence to support this mechanism was provided by characterization of the enzyme half-reactions. Membranes incubated with acetyl-CoA and [ 3 H]CoA were found to produce acetyl-[ 3 H]CoA. This exchange was optimal at pH values above 7.0. Treating membranes with [ 3 H] acetyl-CoA resulted in the formation of an acetyl-enzyme intermediate. The acetyl group could then be transferred to glucosamine, forming [ 3 H]N-acetylglucosamine. The transfer of the acetyl group from the enzyme to glucosamine was optimal between pH 4 and 5. The results suggest that acetyl-CoA does not cross the lysosomal membrane. Instead, the enzyme is acetylated on the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate

Hypochlorite-mediated fragmentation of hyaluronan, chondroitin sulfates, and related N-acetyl glycosamines

DEFF Research Database (Denmark)

Rees, Martin D; Hawkins, Clare Louise; Davies, Michael Jonathan

2003-01-01

Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the presence of chloride ions to give hypochlorous acid. This oxidant has been implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and chondroitin sulfates. In this study it is shown that reaction...... processes. In the case of glycosaminoglycan-derived amidyl radicals, evidence has been obtained in studies with model glycosides that these radicals undergo rapid intramolecular abstraction reactions to give carbon-centered radicals at C-2 on the N-acetyl glycosamine rings (via a 1,2-hydrogen atom shift......) and at C-4 on the neighboring uronic acid residues (via 1,5-hydrogen atom shifts). The C-4 carbon-centered radicals, and analogous species derived from model glycosides, undergo pH-independent beta-scission reactions that result in glycosidic bond cleavage. With N-acetyl glucosamine C-1 alkyl glycosides...

Fluorinated Analogs of Malachite Green: Synthesis and Toxicity

Directory of Open Access Journals (Sweden)

Bahram Parvin

2008-04-01

Full Text Available A series of fluorinated analogs of malachite green (MG have been synthesizedand their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell lineexamined. The toxicity profiles were found to be different for these two species. Twoanalogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem tobe the most promising analogs because they showed the lowest toxicity to the human cells.

Sample preparation techniques for the determination of natural 15N/14N variations in amino acids by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS).

Science.gov (United States)

Hofmann, D; Gehre, M; Jung, K

2003-09-01

In order to identify natural nitrogen isotope variations of biologically important amino acids four derivatization reactions (t-butylmethylsilylation, esterification with subsequent trifluoroacetylation, acetylation and pivaloylation) were tested with standard mixtures of 17 proteinogenic amino acids and plant (moss) samples using GC-C-IRMS. The possible fractionation of the nitrogen isotopes, caused for instance by the formation of multiple reaction products, was investigated. For biological samples, the esterification of the amino acids with subsequent trifluoroacetylation is recommended for nitrogen isotope ratio analysis. A sample preparation technique is described for the isotope ratio mass spectrometric analysis of amino acids from the non-protein (NPN) fraction of terrestrial moss. 14N/15N ratios from moss (Scleropodium spec.) samples from different anthropogenically polluted areas were studied with respect to ecotoxicologal bioindication.

Annotating Enzymes of Uncertain Function: The Deacylation of d-Amino Acids by Members of the Amidohydrolase Superfamily

Energy Technology Data Exchange (ETDEWEB)

Cummings, J.; Fedorov, A; Xu, C; Brown, S; Fedorov, E; Babbitt, P; Almo, S; Raushel, F

2009-01-01

The catalytic activities of three members of the amidohydrolase superfamily were discovered using amino acid substrate libraries. Bb3285 from Bordetella bronchiseptica, Gox1177 from Gluconobacter oxidans, and Sco4986 from Streptomyces coelicolor are currently annotated as d-aminoacylases or N-acetyl-d-glutamate deacetylases. These three enzymes are 22-34% identical to one another in amino acid sequence. Substrate libraries containing nearly all combinations of N-formyl-d-Xaa, N-acetyl-d-Xaa, N-succinyl-d-Xaa, and l-Xaa-d-Xaa were used to establish the substrate profiles for these enzymes. It was demonstrated that Bb3285 is restricted to the hydrolysis of N-acyl-substituted derivatives of d-glutamate. The best substrates for this enzyme are N-formyl-d-glutamate (k{sub cat}/K{sub m} = 5.8 x 10{sup 6} M{sup -1} s{sup -1}), N-acetyl-d-glutamate (k{sub cat}/K{sub m} = 5.2 x 10{sup 6} M{sup -1} s{sup -1}), and l-methionine-d-glutamate (k{sub cat}/K{sub m} = 3.4 x 10{sup 5} M{sup -1} s{sup -1}). Gox1177 and Sco4986 preferentially hydrolyze N-acyl-substituted derivatives of hydrophobic d-amino acids. The best substrates for Gox1177 are N-acetyl-d-leucine (k{sub cat}/K{sub m} = 3.2 x 104 M{sup -1} s-1), N-acetyl-d-tryptophan (kcat/Km = 4.1 x 104 M-1 s-1), and l-tyrosine-d-leucine (kcat/Km = 1.5 x 104 M-1 s-1). A fourth protein, Bb2785 from B. bronchiseptica, did not have d-aminoacylase activity. The best substrates for Sco4986 are N-acetyl-d-phenylalanine and N-acetyl-d-tryptophan. The three-dimensional structures of Bb3285 in the presence of the product acetate or a potent mimic of the tetrahedral intermediate were determined by X-ray diffraction methods. The side chain of the d-glutamate moiety of the inhibitor is ion-paired to Arg-295, while the {alpha}-carboxylate is ion-paired with Lys-250 and Arg-376. These results have revealed the chemical and structural determinants for substrate specificity in this protein. Bioinformatic analyses of an additional {approx}250

Composition of amino acid using carbon monoxide. Amide carbonylation reaction

Energy Technology Data Exchange (ETDEWEB)

Izawa, Kunisuke (Ajinomoto Co., Inc., Tokyo (Japan))

1989-02-01

Amide carbonylation reaction is a method to compose N-acyl-{alpha}-amino acid from aldehyde, carboxylic acid amide, and carbon monoxide in a phase and with high yield. Unlike the conventional Strecker reaction, this method does not use HCN which is in question on public pollution and does not require hydrolysis. This amide carbonylation reaction was discovered by Wakamatsu and others of Ajinomoto Co.,Ltd. Present application examples of this method are the composition of N-acetyl amino acid from the aldehyde class, the composition of N-Acyl amino acid from olefin, the composition of N-acyl or acetyl amino acid from the raw material of alcohol and the halide class, the composition of N-acyl or acetyl amino acid via the isomerization of epoxide and allyl alcohol, the composition of amino dicarboxylic acid, applying deoxidation of ring acid anhydride, the composition of N-acyl amino acid from the raw material of the amine class, the stereoselective composition of -substitution ring-{alpha}-amino acid, and the composition of amino aldehyde. 24 refs., 2 figs., 2 tabs.

Comparative analysis of pharmacological treatments with N-acetyl-DL-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

Science.gov (United States)

Tighilet, Brahim; Leonard, Jacques; Bernard-Demanze, Laurence; Lacour, Michel

2015-12-15

Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only. Copyright © 2015 Elsevier B.V. All rights reserved.

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in food and related products is essential for understanding their nutritive importance. .... (prepared solution), with 0.1 M nitric acid in order to check the linearity. ..... Shahidi, F.; Naczk, M. Food Phenolics: An overview in Food Phenolics: Sources ...

Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

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Zhang, Yi; Tay, JooHwa

2015-04-09

Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of N-terminal acetylation on micelle-induced conformational changes and aggregation of α-Synuclein.

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David Ruzafa

Full Text Available The biological function of α-Synuclein has been related to binding to lipids and membranes but these interactions can also mediate α-Synuclein aggregation, which is associated to Parkinson's disease and other neuropathologies. In brain tissue α-Synuclein is constitutively N-acetylated, a modification that plays an important role in its conformational propensity, lipid and membrane binding, and aggregation propensity. We studied the interactions of the lipid-mimetic SDS with N-acetylated and non-acetylated α-Synuclein, as well as their early-onset Parkinson's disease variants A30P, E46K and A53T. At low SDS/protein ratios α-Synuclein forms oligomeric complexes with SDS micelles with relatively low α-helical structure. These micellar oligomers can efficiently nucleate aggregation of monomeric α-Synuclein, with successive formation of oligomers, protofibrils, curly fibrils and mature amyloid fibrils. N-acetylation reduces considerably the rate of aggregation of WT α-Synuclein. However, in presence of any of the early-onset Parkinson's disease mutations the protective effect of N-acetylation against micelle-induced aggregation becomes impaired. At higher SDS/protein ratios, N-acetylation favors another conformational transition, in which a second type of α-helix-rich, non-aggregating oligomers become stabilized. Once again, the Parkinson's disease mutations disconnect the influence of N-acetylation in promoting this transition. These results suggest a cooperative link between the N-terminus and the region of the mutations that may be important for α-Synuclein function.

40 CFR Table 2 to Subpart Ooo of... - Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins

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2010-07-01

... (HAP) From the Manufacture of Amino/Phenolic Resins 2 Table 2 to Subpart OOO of Part 63 Protection of... Pollutant Emissions: Manufacture of Amino/Phenolic Resins Pt. 63, Subpt. OOO, Table 2 Table 2 to Subpart OOO of Part 63—Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins...

Amino phenolics from the fruit of the argan tree Argania spinosa (Skeels L.).

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Klika, D; Khallouki, Farid; Owen, Robert W

2014-01-01

A new phenolic-type compound containing a nitrogenous, heterocyclic-fused ring from the fruit of the argan tree, Argania spinosa (Skeels L.), is described. This and another already known compound also isolated in the course of the work belong to an obscure and rare class of natural products, the amino phenolics.

Facile and Efficient Acetylation of Primary Alcohols and Phenols with Acetic Anhydride Catalyzed by Dried Sodium Bicarbonate

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Fulgentius Nelson Lugemwa

2013-12-01

Full Text Available A variety of primary alcohols and phenols were reacted with acetic anhydride at room temperature in the presence of sodium bicarbonate to produce corresponding esters in good to excellent yields. The acetylation of 4-nitrobenzyl alcohol was also carried out using other bicarbonates and carbonates. The reaction in the presence of cesium bicarbonate and lithium carbonate gave 4-nitrobenzyl acetate in excellent yield, while in the presence of Na2CO3, K2CO3, Cs2CO3, or KHCO3 the yield was in the range of 80%–95%. Calcium carbonate and cobaltous carbonate did not promote the acetylation of 4-ntirobenzyl alcohol using acetic anhydride. The acetylation of 4-nitrobenzyl alcohol was carried out using ethyl acetate, THF, toluene, diethyl ether, dichloromethane and acetonitrile, and gave good yields ranging from 75%–99%. Toluene was the best solvent for the reaction, while diethyl ether was the poorest.

Sesquiterpene amino ether and cytotoxic phenols from Dendrobium wardianum Warner.

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Zhang, Cong; Liu, Shou-Jin; Yang, Liu; Yuan, Ming-Yan; Li, Jin-Yu; Hou, Bo; Li, Hong-Mei; Yang, Xing-Zhi; Ding, Chang-Chun; Hu, Jiang-Miao

2017-10-01

A new bibenzyl derivative, dendrocandin V (1) and a new sesquiterpene amino ether, wardianumine A (2), together with eleven known compounds, including phenanthrenes (denbinobin (3), 9,10-dihydro-denbinobin (4), mostatin (5), loddigesiinols A (6)), bibenzyls (moscatilin (7), 5-hydroxy-3,4'-dimethoxybibenzyl (8), 3,4-dihydroxy-5,4'-dimethoxy bibenzyl (9), dendrocandin A (10), gigantol (11), dendrocandin U (12)) and an alkaloids (dihydroshihunine, 13) were isolated from the EtOH extraction of stems of Dendrobium wardianum Warner. Isolation of the new compound 2 indicated that N,N-dimethylethanolamine as the key adduction in the synthesis of dendroxine and its analogs in Dendrobium species. The hypothetical biosynthetic pathway of 2 was then postulated. Inspired by literature and traditional usage of the herbal medicine, some compounds were sent for cytotoxic activity and the results indicated that compounds 1, 3, 4, 5 showed cytotoxic activities against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW-480) with IC50 from 2.33-38.48μM. Among those compounds, 3 and 4 showed cell line selectivity with strong activity comparable to DDP. Copyright © 2017. Published by Elsevier B.V.

Acute Toxicity of a Recently Identified Phenol-based Synthetic ...

African Journals Online (AJOL)

This paper reports on the acute toxicity of a new phenol based synthetic tsetse fly repellent recently identified at the International Centre for Insect Physiology and Ecology (patent No. ... The repellent can be classified as being highly toxic with central nervous system (CNS) involvement and a mild skin and eye irritant.

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

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Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs.

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Lund, Kaleb C; Peterson, LaRae L; Wallace, Kendall B

2007-07-01

Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 microM; 2.7 and 13.4 microg/ml), didanosine (ddI) (10 and 50 microM; 2.4 and 11.8 microg/ml), and zalcitabine (ddC) (1 and 5 microM; 0.21 and 1.1 microg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 microg/ml; 1.3 microM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 microM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard.

N-Acetyl-4-aminophenol (paracetamol), N-acetyl-2-aminophenol and acetanilide in urine samples from the general population, individuals exposed to aniline and paracetamol users.

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Dierkes, Georg; Weiss, Tobias; Modick, Hendrik; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger M

2014-01-01

Epidemiological studies suggest associations between the use of N-acetyl-4-aminophenol (paracetamol) during pregnancy and increased risks of reproductive disorders in the male offspring. Previously we have reported a ubiquitous urinary excretion of N-acetyl-4-aminophenol in the general population. Possible sources are (1) direct intake of paracetamol through medication, (2) paracetamol residues in the food chain and (3) environmental exposure to aniline or related substances that are metabolized into N-acetyl-4-aminophenol. In order to elucidate the origins of the excretion of N-acetyl-4-aminophenol in urine and to contribute to the understanding of paracetamol and aniline metabolism in humans we developed a rapid, turbulent-flow HPLC-MS/MS method with isotope dilution for the simultaneous quantification of N-acetyl-4-aminophenol and two other aniline related metabolites, N-acetyl-2-aminophenol and acetanilide. We applied this method to three sets of urine samples: (1) individuals with no known exposure to aniline and also no recent paracetamol medication; (2) individuals after occupational exposure to aniline but no paracetamol medication and (3) paracetamol users. We confirmed the omnipresent excretion of N-acetyl-4-aminophenol. Additionally we revealed an omnipresent excretion of N-acetyl-2-aminophenol. In contrast, acetanilide was only found after occupational exposure to aniline, not in the general population or after paracetamol use. The results lead to four preliminary conclusions: (1) other sources than aniline seem to be responsible for the major part of urinary N-acetyl-4-aminophenol in the general population; (2) acetanilide is a metabolite of aniline in man and a valuable biomarker for aniline in occupational settings; (3) aniline baseline levels in the general population measured after chemical hydrolysis do not seem to originate from acetanilide and hence not from a direct exposure to aniline itself and (4) N-acetyl-2-aminophenol does not seem to be

A Biodistribution and Toxicity Study of Cobalt Dichloride-N-Acetyl Cysteine in an Implantable MRI Marker for Prostate Cancer Treatment

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Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Texas (United States); Johansen, Mary J. [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States); Martirosyan, Karen S. [Department of Physics and Astronomy, The University of Texas at Brownsville, Texas (United States); Gagea, Mihai; Van Pelt, Carolyn S.; Borne, Agatha [Department of Veterinary Medicine, Surgery, and Pathology, The University of Texas MD Anderson Cancer Center, Texas (United States); Carmazzi, Yudith; Madden, Timothy [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States)

2013-03-15

Purpose: C4, a cobalt dichloride-N-acetyl cysteine complex, is being developed as a positive-signal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating the systemic effects of potential leakage from C4 MRI markers within the prostate. Methods and Materials: 9-μL doses (equivalent to leakage from 120 markers in a human) of control solution (0.9% sodium chloride), 1% (proposed for clinical use), and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition in plasma, tissues, feces, and urine were evaluated. Results: No C4-related morbidity or mortality was observed in the biodistribution arm (60 rats). Biodistribution was measurable after 10% C4 injection: cobalt was cleared rapidly from periprostatic tissue; mean concentrations in prostate were 163 μg/g and 268 μg/g at 5 and 30 minutes but were undetectable by 60 minutes. Expected dual renal-hepatic elimination was observed, with percentages of injected dose recovered in tissues of 39.0 ± 5.6% (liver), >11.8 ± 6.5% (prostate), and >5.3 ± 0.9% (kidney), with low plasma concentrations detected up to 1 hour (1.40 μg/mL at 5-60 minutes). Excretion in urine was 13.1 ± 4.6%, with 3.1 ± 0.54% recovered in feces by 24 hours. In the toxicity arm, 3 animals died in the control group and 1 each in the 1% and 10% groups from surgical or anesthesia-related complications; all others survived to scheduled termination at 14 days. No C4-related adverse clinical signs or organ toxicity were observed. Conclusion: C4-related toxicity was not observed at exposures at least 10-fold the exposure proposed for use in humans. These data demonstrating lack of systemic toxicity with dual routes of elimination in the event of in situ rupture suggest that C4 warrants further investigation as an MRI marker for prostate

Plant phenolics and absorption features in vegetation reflectance spectra near 1.66 μm

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Kokaly, Raymond F.; Skidmore, Andrew K

2015-01-01

Past laboratory and field studies have quantified phenolic substances in vegetative matter from reflectance measurements for understanding plant response to herbivores and insect predation. Past remote sensing studies on phenolics have evaluated crop quality and vegetation patterns caused by bedrock geology and associated variations in soil geochemistry. We examined spectra of pure phenolic compounds, common plant biochemical constituents, dry leaves, fresh leaves, and plant canopies for direct evidence of absorption features attributable to plant phenolics. Using spectral feature analysis with continuum removal, we observed that a narrow feature at 1.66 μm is persistent in spectra of manzanita, sumac, red maple, sugar maple, tea, and other species. This feature was consistent with absorption caused by aromatic C-H bonds in the chemical structure of phenolic compounds and non-hydroxylated aromatics. Because of overlapping absorption by water, the feature was weaker in fresh leaf and canopy spectra compared to dry leaf measurements. Simple linear regressions of feature depth and feature area with polyphenol concentration in tea resulted in high correlations and low errors (% phenol by dry weight) at the dry leaf (r2 = 0.95, RMSE = 1.0%, n = 56), fresh leaf (r2 = 0.79, RMSE = 2.1%, n = 56), and canopy (r2 = 0.78, RMSE = 1.0%, n = 13) levels of measurement. Spectra of leaves, needles, and canopies of big sagebrush and evergreens exhibited a weak absorption feature centered near 1.63 μm, short ward of the phenolic compounds, possibly consistent with terpenes. This study demonstrates that subtle variation in vegetation spectra in the shortwave infrared can directly indicate biochemical constituents and be used to quantify them. Phenolics are of lesser abundance compared to the major plant constituents but, nonetheless, have important plant functions and ecological significance. Additional research is needed to advance our understanding of the

Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori.

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Owings, Joshua P; McNair, Nina N; Mui, Yiu Fung; Gustafsson, Tomas N; Holmgren, Arne; Contel, Maria; Goldberg, Joanna B; Mead, Jan R

2016-07-01

Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicate that auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as five auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and five gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro Auranofin completely inhibited bacterial growth at 1.2 μM. Purified H. pylori TrxR was inhibited by auranofin in a cell-free assay (IC50 ∼88 nM). The most active gold(I)-N-heterocyclic carbene compounds exhibited MICs comparable to auranofin against H. pylori (2 μM), while also exhibiting lower toxicities for human embryonic kidney cells (HEK-293T cells). Median toxic concentrations (TC50) were 13-20-fold higher compared to auranofin indicating that they were less cytotoxic. The N-heterocyclic carbene analogs maybe well tolerated, but further evaluation is needed in vivo Finally, auranofin was synergistic with the antibiotic amoxicillin, suggesting that targeting both the reductive enzyme TrxR and cell wall synthesis may be effective against H. pylori infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antimicrobial activity against Porphyromonas gingivalis and mechanism of action of the cationic octadecapeptide AmyI-1-18 and its amino acid-substituted analogs.

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Taniguchi, Masayuki; Ochiai, Akihito; Takahashi, Kiyoshi; Nakamichi, Shun-Ichi; Nomoto, Takafumi; Saitoh, Eiichi; Kato, Tetsuo; Tanaka, Takaaki

2016-12-01

The antimicrobial peptide AmyI-1-18 is a cationic α-helical octadecapeptide derived from α-amylase in rice (Oryza sativa L. japonica) that contains four cationic amino acid residues (two arginines and two lysines). To enhance the antibacterial activity of AmyI-1-18 against Porphyromonas gingivalis (a bacterium associated with periodontal disease), we synthesized 12 analogs bearing substitutions with alanine, leucine, and/or arginine that were designed based on helical wheel projections and investigated their antibacterial properties. The antibacterial properties of four analogs bearing substitution of a single arginine or lysine with alanine were almost similar to those of AmyI-1-18, suggesting that the antibacterial properties depend on the presence of three cationic amino acid residues. Of three single arginine-substituted analogs, AmyI-1-18(G12R) exhibited an antibacterial activity 2.8-fold higher [50% growth-inhibitory concentration (IC 50 ): 4.6 μM] than that of AmyI-1-18 (IC 50 : 13 μM). Likewise, the antibacterial properties of two single leucine-substituted analogs were significantly enhanced; in particular, AmyI-1-18(N3L) exhibited an antibacterial activity (IC 50 : 2.5 μM) 5.2-fold higher than that of AmyI-1-18. The hemolytic activity of AmyI-1-18(N3L) against mammalian red blood cells was low (2% at 50 μM). A membrane-depolarization assay using a membrane potential-sensitive fluorescent dye revealed that, similar to AmyI-1-18, the antibacterial activity of AmyI-1-18(N3L) was not dependent on its membrane-disrupting activity. Our results demonstrate that the antibacterial properties of AmyI-1-18 against P. gingivalis are significantly improved, without a significant increase in hemolytic activity, by replacing asparagine with leucine at position 3. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Toxicity of copper chelates of azomethines and amino acids for Chlorella pyrenoidosa

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Barashkov, G.K.; Rukhadze, E.G.; Talyzenkova, G.P.

1979-01-01

The authors have attempted to assess the toxicity of copper-containing compounds from the point of view of their interrelationship with the structural characteristics of the chelate compound and the structure of the ligand. The copper chelates of the azomethines tested may be provisionally divided into three types: A - complexes with N-alkly-azomethines; B - complexes with N-aryl-azomethines; C - binuclear complexes. Consideration was also given to chelates with aromatic and heterocyclic amino acids and to heteroligand chelates in which the copper atom coordinates azomethine and an amino acid simultaneously. Toxicity was determined by the method previously described and expressed as a critical concentration (C/sub cr/, mg Cu/liter) and in relative toxicity units (T/sub c/). The compounds investigated were obtained from the interaction between a bidentant ligand of an azomethine or anamino acid and copper acetate in a water-alcohol medium at pH 6-8. Since they are not very soluble in water, true solutions were obtained by using dimethyl sulfoxide.

Measuring urinary N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPMA3) as a potential biomarker of isoprene exposure.

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Alwis, K Udeni; Bailey, T Liz; Patel, Dhrusti; Wang, Liqun; Blount, Benjamin C

2016-10-19

Isoprene, the 2-methyl analog of 1,3-butadiene, is identified as a possible human carcinogen by the International Agency for Research on Cancer (IARC). Isoprene is ubiquitous in the environment with numerous natural and anthropogenic sources. Tobacco smoke is the main exogenous source of isoprene exposure in indoor environments. Among smoke constituents, isoprene is thought to contribute significantly to cancer risk; however, no selective urinary biomarkers of isoprene exposure have been identified for humans. In this manuscript, we measured the minor isoprene metabolite IPMA1 (mixture of N-acetyl-S-(1-[hydroxymethyl]-2-methyl-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-methyl-3-buten-1-yl)-L-cysteine), and we identified IPMA3 (N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine) as a major isoprene metabolite and novel isoprene exposure biomarker for humans. Urinary isoprene metabolites were measured using ultra high performance liquid chromatography coupled with electrospray ionization triple quad tandem mass spectrometry (UPLC/ESI-MSMS). The detection rates of IPMA1 and IPMA3 are <20% and 82%, respectively. The selectivity and abundance of IPMA3 make it a useful urinary biomarker of isoprene exposure. The limit of detection of IPMA3 in urine was 0.5 ng mL -1 . IPMA3 was stable under different storage temperatures and following ten freeze-thaw cycles. The average recovery of urine spiked with IPMA3 at three different levels was 99%. IPMA3 was measured in urine samples received from 75 anonymous subjects; the median (25th percentile, 75th percentile) IPMA3 level in smokers was 36.2 (18.2, 56.8) ng mL -1 and non-smokers 2.31 (2.31, 4.38) ng mL -1 . Application of this method to large population studies will help to characterize isoprene exposure and assess potential health impact. Published by Elsevier B.V.

Synthesis of some labelled non-proteinogenic amino acids

International Nuclear Information System (INIS)

Adrianens, P.; Vanderhaeghe, H.

1987-01-01

The literature on the synthesis of labeled non-proteinogenic amino acids contains approximately 300 papers, whereas syntheses of labeled proteinogenic amino acids are dealt with in some 800-1000 publications. However, most of the methods described in this paper for the synthesis of non-proteinogenic amino acids are also used for the preparation of the essential amino acids addition, the first category also contains β, γ...amino acids, seleno amino acids, N-methyl and α-methyl amino acids and sometimes have atoms or groups which are not present in the protein building blocks. Furthermore the latter group is more easily available so that methods for synthesis of non-proteinogenic amino acids are more needed

Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits

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Bioassay-guided isolation and purification of the ethyl acetate extract of Moringa oleifera fruits yielded three new phenolic glycosides; 4-[(2'-O-acetyl-a-L-rhamnosyloxy) benzyl]isothiocyanate (1), 4-[(3'-O-acetyl-a-L-rhamnosyloxy)benzyl]isothiocyanate (2), and S-methyl-N-{4-[(a-L-rhamnosyloxy)benz...

21 CFR 172.372 - N-Acetyl-L-methionine.

Science.gov (United States)

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.372 N-Acetyl-L-methionine. The food additive N-acetyl-L...

Radiosynthesis and in vitro evaluation of 2-(N-alkyl-N-1'-11C-propyl)amino-5-hydroxytetralin analogs as high affinity agonists for dopamine D-2 receptors

International Nuclear Information System (INIS)

Shi Bingzhi; Narayanan, Tanjore K.; Yang, Z.-Y.; Christian, Bradley T.; Mukherjee, Jogeshwar

1999-01-01

We have developed radiotracers based on agonists that may potentially allow the in vivo assessment of the high affinity (HA) state of the dopamine D-2 receptors. The population of HA state, which is likely the functional state of the receptor, may be altered in certain diseases. We carried out radiosyntheses and evaluated the binding affinities, lipophilicity, and in vitro autoradiographic binding characteristics of three dopamine D-2 receptor agonists: (±)-2-(N,N-dipropyl)amino-5-hydroxytetralin (5-OH-DPAT), (±)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), and (±)-2-(N-cyclohexylethyl-N-propyl)amino-5-hydroxytetralin (ZYY-339). In 3 H-spiperone assays using rat striata, ZYY-339 exhibited subnanomolar affinity for D-2 receptor sites ( IC 50 =0.010 nM), PPHT was somewhat weaker ( IC 50 =0.65 nM), and 5-OH-DPAT exhibited the weakest affinity ( IC 50 =2.5 nM) of the three compounds. Radiosynthesis of these derivatives, 2-(N-propyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-5-OH-DPAT), 2-(N-phenethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-PPHT), and 2-(N-cyclohexylethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-ZYY-339) was achieved by first synthesizing 11 C-1-propionyl chloride and subsequent coupling with the appropriate secondary amine precursor to form the respective amide, which was then reduced to provide the desired tertiary amine products. The final products were obtained by reverse-phase high performance liquid chromatography (HPLC) purification in radiochemical yields of 5-10% after 60-75 min from the end of 11 CO 2 trapping and with specific activities in the range of 250-1,000 Ci/mmol. In vitro autoradiographs in rat brain slices with 11 C-5-OH-DPAT, 11 C-PPHT, and 11 C-ZYY-339 revealed selective binding of the three radiotracers to the dopamine D-2 receptors in the striata

Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates.

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Lui, Matthew Y; Yuen, Alexander K L; Masters, Anthony F; Maschmeyer, Thomas

2016-09-08

An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural, kinetic and proteomic characterization of acetyl phosphate-dependent bacterial protein acetylation.

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Misty L Kuhn

Full Text Available The emerging view of Nε-lysine acetylation in eukaryotes is of a relatively abundant post-translational modification (PTM that has a major impact on the function, structure, stability and/or location of thousands of proteins involved in diverse cellular processes. This PTM is typically considered to arise by the donation of the acetyl group from acetyl-coenzyme A (acCoA to the ε-amino group of a lysine residue that is reversibly catalyzed by lysine acetyltransferases and deacetylases. Here, we provide genetic, mass spectrometric, biochemical and structural evidence that Nε-lysine acetylation is an equally abundant and important PTM in bacteria. Applying a recently developed, label-free and global mass spectrometric approach to an isogenic set of mutants, we detected acetylation of thousands of lysine residues on hundreds of Escherichia coli proteins that participate in diverse and often essential cellular processes, including translation, transcription and central metabolism. Many of these acetylations were regulated in an acetyl phosphate (acP-dependent manner, providing compelling evidence for a recently reported mechanism of bacterial Nε-lysine acetylation. These mass spectrometric data, coupled with observations made by crystallography, biochemistry, and additional mass spectrometry showed that this acP-dependent acetylation is both non-enzymatic and specific, with specificity determined by the accessibility, reactivity and three-dimensional microenvironment of the target lysine. Crystallographic evidence shows acP can bind to proteins in active sites and cofactor binding sites, but also potentially anywhere molecules with a phosphate moiety could bind. Finally, we provide evidence that acP-dependent acetylation can impact the function of critical enzymes, including glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase, and RNA polymerase.

Effect of acetylator genotype on the levels of carcinogen-DNA adducts in inbred hamsters treated with 2-aminofluorene

International Nuclear Information System (INIS)

Flammang, T.J.; Yerokun, T.; Hein, D.W.; Talaska, G.; Kirlin, W.G.; Ogolla, F.; Ferguson, R.J.

1990-01-01

A genetic polymorphism in N-acetyltransferase has been described previously in humans and in animal models that is known to affect an individual's susceptibility to certain drug toxicities and diseases including bladder cancer. In hamsters, the polymorphism is known to regulate the conversion of carcinogenic 2-aminofluorene to its amide and of N-hydroxy-2-aminofluorene to a reactive electrophile that forms a covalently-bound adduct with DNA; an event thought to initiate the tumorigenic process. A single dose of 2-aminofluorene (60 mg/kg body wt., i.p) was administered to homozygous rapid- (rr) and homozygous slow-acetylator (ss) hamsters, and the levels of aminofluorene-DNA adducts in bladder and liver were evaluated by a 32 P-postlabeling assay. Only a non-acetylated aminofluorene-DNA adduct was detected in the DNA samples. In this study, no differences were detected between the levels of hepatic 2-aminofluorene-DNA adducts in males or females or between the rr or ss hamsters. In contrast, the levels of 2-amino-fluorene-adducts in bladder DNA were 5-fold higher in the male rr than in the ss hamsters, and were 2-fold higher in the male rr than in the female rr animals

Preliminary observations and clinical value of N-acetyl resonances in ovarian tumours using in-vivo proton MR spectroscopy at 3T

Energy Technology Data Exchange (ETDEWEB)

Takeuchi, Mayumi; Matsuzaki, Kenji; Harada, Masafumi [University of Tokushima, Department of Radiology, Tokushima (Japan)

2011-12-15

To retrospectively evaluate the clinical significance of N-acetyl resonances at 2 ppm in in-vivo proton magnetic resonance (MR) spectroscopy for distinguishing mucinous and non-mucinous tumours in patients with ovarian masses. MR spectroscopy was performed in patients with pathologically diagnosed ovarian tumours at 3T-MR imaging. Single-voxel MR spectroscopy data were collected from a single square volume of interest that encompassed the ovarian masses. The metabolite resonance peak areas at 2 ppm were quantified relative to unsuppressed water using a software package (LCModel). A total of 32 ovarian lesions in 32 patients were evaluated in this study. High metabolite peak at 2 ppm was observed in all nine mucinous tumours (9.71 +/- 7.46 mM), whereas low peak was observed in 14 of 23 non-mucinous tumours (3.12 +/- 1.42 mM) (p < 0.001). Using a cut off value of 4.45 mM for mucinous tumours had a sensitivity of 89%, specificity of 86%, PPV of 80%, and NPV of 92%. Proton MR spectroscopy with quantitative evaluation of the metabolite at 2 ppm concentration, which may suggest the presence of mucinous material containing N-acetyl mucinous compounds, can provide helpful information in distinguishing mucinous and non-mucinous ovarian tumours. (orig.)

N-Acetyl-S-(n-Propyl)-L-Cysteine in Urine from Workers Exposed to 1-Bromopropane in Foam Cushion Spray Adhesives

Science.gov (United States)

Hanley, Kevin W.; Petersen, Martin R.; Cheever, Kenneth L.; Luo, Lian

2009-01-01

1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br(−)] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br(−) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers. PMID:19706636

Sulphur-containing Amino Acids: Protective Role Against Free Radicals and Heavy Metals.

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Colovic, Mirjana B; Vasic, Vesna M; Djuric, Dragan M; Krstic, Danijela Z

2018-01-30

Sulphur is an abundant element in biological systems, which plays an important role in processes essential for life as a constituent of proteins, vitamins and other crucial biomolecules. The major source of sulphur for humans is plants being able to use inorganic sulphur in the purpose of sulphur-containing amino acids synthesis. Sulphur-containing amino acids include methionine, cysteine, homocysteine, and taurine. Methionine and cysteine are classified as proteinogenic, canonic amino acids incorporated in protein structure. Sulphur amino acids are involved in the synthesis of intracellular antioxidants such as glutathione and N-acetyl cysteine. Moreover, naturally occurring sulphur-containing ligands are effective and safe detoxifying agents, often used in order to prevent toxic metal ions effects and their accumulation in human body. Literature search for peer-reviewed articles was performed using PubMed and Scopus databases, and utilizing appropriate keywords. This review is focused on sulphur-containing amino acids - methionine, cysteine, taurine, and their derivatives - glutathione and N-acetylcysteine, and their defense effects as antioxidant agents against free radicals. Additionally, the protective effects of sulphur-containing ligands against the toxic effects of heavy and transition metal ions, and their reactivation role towards the enzyme inhibition are described. Sulphur-containing amino acids represent a powerful part of cell antioxidant system. Thus, they are essential in the maintenance of normal cellular functions and health. In addition to their worthy antioxidant action, sulphur-containing amino acids may offer a chelating site for heavy metals. Accordingly, they may be supplemented during chelating therapy, providing beneficial effects in eliminating toxic metals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Capillary electrophoretic determination of selected phenolic compounds in humic substances of well waters and fertilizers.

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Chen, Mei-Ying; Chang, Yan-Zin; Lu, Fung-Jou; Chen, Jian-Lian

2010-01-01

Humic substances (HS) from well waters, fertilizers, and synthetic phenolic polymers were characterized by elemental and UV-VIS spectroscopic analyses. Capillary zone electrophoresis (CZE) with UV absorption detection was used to analyze the lignin-derived phenolic distribution in the degradation residues after alkaline CuO oxidation of HS samples. Eleven phenols with p-acetyl, vanillyl and syringyl substituents were selected to optimize the CZE parameters. For well waters and fertilizers, the content of phenolic fragments was in agreement with the findings of the elemental and spectroscopic measurements. Additionally, parameters derived from the vanillic acid/vanilline, syringyl acid/syringaldehyde, p-hydroxyl/vanillyl and syringyl/vanillyl ratios matched analogous studies on dissolved organic matter from natural waters and on humic acids from terrestrial substances. The amount of phenolic monomer bonded within two synthetic HS polymers was found to be 25.9% protocatechuic acid and 71.3% gallic acid.

N-acetyl-l-cysteine and Mn2+ attenuate Cd2+-induced disturbance of the intracellular free calcium homeostasis in cultured cerebellar granule neurons.

Science.gov (United States)

Isaev, Nickolay K; Avilkina, Svetlana; Golyshev, Sergey A; Genrikhs, Elisaveta E; Alexandrova, Olga P; Kapkaeva, Marina R; Stelmashook, Elena V

2018-01-15

Cadmium is a highly toxic heavy metal that is capable of accumulating in the body via direct exposure or through the alimentary and respiratory tract, leading to neurodegeneration. In this article, we show that the application of CdCl 2 (0.001-0.005mM) for 48h induced high dose-dependent death rate of cultured cerebellar granule neurons (CGNs). Unlike Trolox or vitamin E, antioxidant N-acetyl-l-cysteine (NAC, 1mM) and Mn 2+ (0.0025-0.005mM) significantly protected CGNs from this toxic effect. Using Fluo-4 AM, measurements of intracellular calcium ions demonstrated that 24h-exposure to Cd 2+ induced intensive increase of Fluo-4 fluorescence in neurons accompanied by mitochondria swelling. These data imply that the cadmium-induced Ca 2+ increase is an important element in the death of neurons due to toxic effect of cadmium and the mechanism of protective action of manganese and NAC is mediated by the prevention of increase in calcium levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Phosphorylation and Acetylation of Acyl-CoA Synthetase- I

DEFF Research Database (Denmark)

Frahm, Jennifer L; Li, Lei O; Grevengoed, Trisha J

2011-01-01

Long chain acyl-CoA synthetase 1 (ACSL1) contributes 50 to 90% of total ACSL activity in liver, adipose tissue, and heart and appears to direct the use of long chain fatty acids for energy. Although the functional importance of ACSL1 is becoming clear, little is understood about its post...... and acetylated amino acids by mass spectrometry. We then compared these results to the post-translational modifications observed in vivo in liver and brown adipose tissue after mice were fasted or exposed to a cold environment. We identified universal N-terminal acetylation, 15 acetylated lysines, and 25...

Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin.

Science.gov (United States)

Xiong, Jian; Bhaskar, Ujjwal; Li, Guoyun; Fu, Li; Li, Lingyun; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

2013-09-10

Heparin is a critically important anticoagulant drug that is prepared from pig intestine. In 2007-2008, there was a crisis in the heparin market when the raw material was adulterated with the toxic polysaccharide, oversulfated chondroitin sulfate, which was associated with 100 deaths in the U.S. alone. As the result of this crisis, our laboratory and others have been actively pursuing alternative sources for this critical drug, including synthetic heparins and bioengineered heparin. In assessing the bioengineering processing costs it has become clear that the use of both enzyme-catalyzed cofactor recycling and enzyme immobilization will be needed for commercialization. In the current study, we examine the use of immobilization of C₅-epimerase and 2-O-sulfotransferase involved in the first enzymatic step in the bioengineered heparin process, as well as arylsulfotransferase-IV involved in cofactor recycling in all three enzymatic steps. We report the successful immobilization of all three enzymes and their use in converting N-sulfo, N-acetyl heparosan into N-sulfo, N-acetyl 2-O-sulfo heparin. Copyright © 2013 Elsevier B.V. All rights reserved.

Highly-sensitive electrocatalytic determination for toxic phenols based on coupled cMWCNT/cyclodextrin edge-functionalized graphene composite

Energy Technology Data Exchange (ETDEWEB)

Gao, Juanjuan; Liu, Maoxiang [School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Song, Haiou, E-mail: songhaiou2011@126.com [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Zhang, Shupeng, E-mail: shupeng_2006@126.com [School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Qian, Yueyue [School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Li, Aimin, E-mail: liaimin@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

2016-11-15

Highlights: • Phenol detection based on coupled cMWCNT/CD edge-functionalized graphene composite. • Increased conductivity can inspire enhancement of electrocatalytic performance. • The synergistic combination of the trace amounts of CDs and cMWCNT is a pivotal. • GN-CD-cMWCNT shows an excellent electrocatalytic and anti-interference ability. - Abstract: Highly-sensitive electrocatalytic determination of toxic phenol compounds is of significance in environmental monitoring due to their low degradation and high toxicity to the environment and humans. In this paper, a rapid and sensitive electrochemical sensor based on coupled carboxyl-multi-walled carbon nanotube (cMWCNT) and cyclodextrin (CD) edge-functionalized graphene composite was successfully employed towards trace detection of three typical phenols (4-aminophenol, 4-AP; 4-chlorophenol, 4-CP; 4-nitrophenol, 4-NP). The morphology studies from scanning electron microscope and transmission electron microscope analysis revealed that cMWCNTs as conductive bridges were successfully incorporated into CD edge-functionalized graphene layers. Further, The electrocatalytic detection performance of the 3D simultaneously reduced and self-assembled sensing architecture (GN-CD-cMWCNT) with trace amounts of CDs was evaluated. The electrochemical studies demonstrated that GN-CD-cMWCNT displays excellent electrocatalytic activity, high sensitivity and stability. Under optimal conditions, the current responses of 4-AP, 4-CP and 4-NP are linear to concentrations over two different ranges, with low detection limit of 0.019, 0.017 and 0.027 μM (S/N = 3), respectively. And, GN-CD-cMWCNT shows an excellent anti-interference ability against electroactive species and metal ions. In addition, validation of the applicability of the presented sensor was also performed for the determination of three phenols in tap water sample with satisfactory results.

Highly-sensitive electrocatalytic determination for toxic phenols based on coupled cMWCNT/cyclodextrin edge-functionalized graphene composite

International Nuclear Information System (INIS)

Gao, Juanjuan; Liu, Maoxiang; Song, Haiou; Zhang, Shupeng; Qian, Yueyue; Li, Aimin

2016-01-01

Highlights: • Phenol detection based on coupled cMWCNT/CD edge-functionalized graphene composite. • Increased conductivity can inspire enhancement of electrocatalytic performance. • The synergistic combination of the trace amounts of CDs and cMWCNT is a pivotal. • GN-CD-cMWCNT shows an excellent electrocatalytic and anti-interference ability. - Abstract: Highly-sensitive electrocatalytic determination of toxic phenol compounds is of significance in environmental monitoring due to their low degradation and high toxicity to the environment and humans. In this paper, a rapid and sensitive electrochemical sensor based on coupled carboxyl-multi-walled carbon nanotube (cMWCNT) and cyclodextrin (CD) edge-functionalized graphene composite was successfully employed towards trace detection of three typical phenols (4-aminophenol, 4-AP; 4-chlorophenol, 4-CP; 4-nitrophenol, 4-NP). The morphology studies from scanning electron microscope and transmission electron microscope analysis revealed that cMWCNTs as conductive bridges were successfully incorporated into CD edge-functionalized graphene layers. Further, The electrocatalytic detection performance of the 3D simultaneously reduced and self-assembled sensing architecture (GN-CD-cMWCNT) with trace amounts of CDs was evaluated. The electrochemical studies demonstrated that GN-CD-cMWCNT displays excellent electrocatalytic activity, high sensitivity and stability. Under optimal conditions, the current responses of 4-AP, 4-CP and 4-NP are linear to concentrations over two different ranges, with low detection limit of 0.019, 0.017 and 0.027 μM (S/N = 3), respectively. And, GN-CD-cMWCNT shows an excellent anti-interference ability against electroactive species and metal ions. In addition, validation of the applicability of the presented sensor was also performed for the determination of three phenols in tap water sample with satisfactory results.

Identification and characterization of phenol hydroxylase from phenol-degrading Candida tropicalis strain JH8.

Science.gov (United States)

Long, Yan; Yang, Sheng; Xie, Zhixiong; Cheng, Li

2014-09-01

The gene phhY encoding phenol hydroxylase from Candida tropicalis JH8 was cloned, sequenced, and expressed in Escherichia coli. The gene phhY contained an open reading frame of 2130 bp encoding a polypeptide of 709 amino acid residues. From its sequence analysis, it is a member of a family of flavin-containing aromatic hydroxylases and shares 41% amino acid identity with phenol hydroxylase from Trichosporon cutaneum. The recombinant phenol hydroxylase exists as a homotetramer structure with a native molecular mass of 320 kDa. Recombinant phenol hydroxylase was insensitive to pH treatment; its optimum pH was at 7.6. The optimum temperature for the enzyme was 30 °C, and its activity was rapidly lost at temperatures above 60 °C. Under the optimal conditions with phenol as substrate, the K(m) and V(max) of recombinant phenol hydroxylase were 0.21 mmol·L(-1) and 0.077 μmol·L(-1)·min(-1), respectively. This is the first paper presenting the cloning and expression in E. coli of the phenol hydroxylase gene from C. tropicalis and the characterization of the recombinant phenol hydroxylase.

Recovery of Pyruvic Acid using Tri-n-butylamine Dissolved in Non-Toxic Diluent (Rice Bran Oil)

Science.gov (United States)

Pal, Dharm; Keshav, Amit

2016-04-01

An attempt has been made to investigate the effectiveness of the vegetable oil based biocompatible solvent for the separation of pyruvic acid from fermentation broth, by using rice bran oil as natural, non-toxic diluent. Reactive extraction of pyruvic acid (0.1-0.5 k mol/m3) from aqueous solutions has been studied using tri-n-butylamine (TBA; 10-70 %) as an extractant dissolved in non toxic rice bran oil at T = 30 ± 1 °C. Results were presented in terms of distribution coefficient (Kd), extraction efficiency (E %), loading ratio (Z), and complexation constant (\\varphi_{α β }). Extraction equilibrium was interpreted using mass action modeling approach. Based on the extent of loading (Z < 0.5) only (1:1), pyruvic acid: TBA complex was proposed. Equilibrium complexation constant was evaluated to 1.22 m3/k mol. Results obtained are useful in understanding the extraction mechanism.

Amino modified multi-walled carbon nanotubes/polydimethylsiloxane coated stir bar sorptive extraction coupled to high performance liquid chromatography-ultraviolet detection for the determination of phenols in environmental samples.

Science.gov (United States)

Hu, Cong; Chen, Beibei; He, Man; Hu, Bin

2013-07-26

In this work, amino modified multi-walled carbon nanotubes/polydimethylsiloxane (multi-walled carbon nanotubes-4,4'-diaminodiphenylmethane/polydimethylsiloxane, MWCNTs-DDM/PDMS) was synthesized, and utilized as a novel coating for stir bar sorptive extraction (SBSE) of seven phenols (phenol, 2-chlorophenol, 2-nitrophenol, 4-nitrophenol, 2,4-dimethylphenol, p-choro-m-cresol and 2,4,6-trichlorphenol) in environmental water and soil samples, followed by high performance liquid chromatography-ultraviolet detection (HPLC-UV). The prepared MWCNTs-DDM/PDMS coated stir bar was characterized and good preparation reproducibility was obtained with the relative standard deviations (RSDs) ranging from 4.7% to 11.3% (n=9) in one batch, and from 4.8% to 13.9% (n=8) among different batches. Several parameters affecting the extraction of seven target phenols by MWCNTs-DDM/PDMS-SBSE including extraction time, stirring rate, pH, ionic strength, desorption solvent and desorption time were investigated. Under the optimal experimental conditions, the limits of detection (LODs, S/N=3) were found to be in the range of 0.14μg/L (2-nitrophenol) to 1.76μg/L (phenol) and the limits of quantification (LOQs, S/N=10) were found to be in the range of 0.46μg/L (2-nitrophenol) to 5.8μg/L (phenol). The linear range was 5-1000μg/L for phenol and 4-nitrophenol, 1-1000μg/L for 2-nitrophenol and 2-1000μg/L for other phenols, respectively. The RSDs of the developed method were in the range of 6.2-11.6% (n=8, c=10μg/L) and the enrichment factors were from 6.5 to 62.8-fold (theoretical enrichment factor was 100-fold). The proposed method was successfully applied to the analysis of phenols in environmental water and soil samples, and good recoveries were obtained for the spiked samples. The proposed method is simple, highly sensitive and suitable for the analysis of trace phenols in environmental samples with complex matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni

Science.gov (United States)

Bahrami, Yadollah; Franco, Christopher M. M.

2015-01-01

Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins. PMID:25603350

N-Acetyl-Cysteine as Effective and Safe Chelating Agent in Metal-on-Metal Hip-Implanted Patients: Two Cases

Directory of Open Access Journals (Sweden)

Andrea Giampreti

2016-01-01

Full Text Available Systemic toxicity associated with cobalt (Co and chromium (Cr containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014. After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable.

Copper(II) sulfate pentahydrate (CuSO4.5H2O): a green catalyst for solventless acetylation of alcohols and phenols with acetic anhydride

OpenAIRE

Heravi,Majid M.; Behbahani,Farahnaz K.; Zadsirjan,Vahideh; Oskooie,Hossien A.

2006-01-01

Alcohols and phenols were efficiently acetylated with acetic anhydride in the presence of copper (II) sulfate at room temperature in high yields. Álcoois e fenóis foram acetilados eficientemente com anidrido acético na presença de sulfato de cobre (II) em temperatura ambiente, com altos rendimentos.

PCI-GC-MS-MS approach for identification of non-amino organic acid and amino acid profiles.

Science.gov (United States)

Luan, Hemi; Yang, Lin; Ji, Fenfen; Cai, Zongwei

2017-03-15

Alkyl chloroformate have been wildly used for the fast derivatization of metabolites with amino and/or carboxyl groups, coupling of powerful separation and detection systems, such as GC-MS, which allows the comprehensive analysis of non-amino organic acids and amino acids. The reagents involving n-alkyl chloroformate and n-alcohol are generally employed for providing symmetric labeling terminal alkyl chain with the same length. Here, we developed an asymmetric labeling strategy and positive chemical ionization gas chromatography-tandem mass spectrometry (PCI-GC-MS-MS) approach for determination of non-amino organic acids and amino acids, as well as the short chain fatty acids. Carboxylic and amino groups could be selectively labelled by propyl and ethyl groups, respectively. The specific neutral loss of C 3 H 8 O (60Da), C 3 H 5 O 2 (74Da) and C 4 H 8 O 2 (88Da) were useful in the selective identification for qualitative analysis of organic acids and amino acid derivatives. PCI-GC-MS-MS using multiple reaction monitoring (MRM) was applied for semi-quantification of typical non-amino organic acids and amino acids. This method exhibited a wide range of linear range, good regression coefficient (R 2 ) and repeatability. The relative standard deviation (RSD) of targeted metabolites showed excellent intra- and inter-day precision (chloroformate derivatization. Copyright © 2016 Elsevier B.V. All rights reserved.

sup. alpha. N-acetyl derivatives of. beta. -endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice

Energy Technology Data Exchange (ETDEWEB)

Garzon, J.; Sanchez-Blazquez, P. (Cajal Institute, Madrid (Spain))

1991-01-01

{sup {alpha}}N-acetyl human {beta}-endorphin(1-31) injected icv to mice antagonized the analgesic activity of {beta}-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) was partially retained by the shorter peptide {sup {alpha}}N-acetyl human {beta}-endorphin-(1-27) and to a lesser extent by {beta}-endorphin-(1-27), {beta}-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated {beta}-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM ({sup 125}I)-Tyr{sup 27} human {beta}-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC{sub 50} of 0.35 nM, and the rest with an IC{sub 50} of 200 nM. It is suggested that {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins G{sub i}/G{sub 0}.

Co-occurrence of non-toxic (cyanopeptolin) and toxic (microcystin) peptides in a bloom of Microcystis sp. from a Chilean lake.

Science.gov (United States)

Neumann, U; Campos, V; Cantarero, S; Urrutia, H; Heinze, R; Weckesser, J; Erhard, M

2000-06-01

A cyanobacterial bloom occurring in 1998 in lake Tres Pascualas (Concepción/Chile) was found to be dominated by Microcystis sp. The bloom contained both non-toxic (cyanopeptolin-type) and hepatotoxic (microcystin-type) peptides. Cyanopeptolin structure of the non-toxic peptides (called cyanopeptolin VW-1 and VW-2, respectively) was revealed by matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS) of whole cells, showing dominant molecular ions at m/z = 975 and m/z 995, respectively. On post source decay (PSD), both cyanopeptolins showed fragments deriving from Ahp-Phe-MTyr (3-amino-6-hydroxy-2-piperidone), the characteristic partial structure of cyanopeptolins. The amounts of each of the two cyanopeptolins could only roughly be estimated to be >0.1% of bloom material dry weight. In addition the blooms contained microcystins (20 microg/g bloom dry weight as determined by RP-HPLC, 13 microg/g according to ELISA determination). MALDI-TOF-MS revealed several structural variants of microcystin: MCYST-RR (microcystin with Arg and Arg, indicated by m/z 1,038 and confirmed by PSD revealing a m/z = 135 fragment deriving from the Adda side chain, MCYST-FR (microcystin with Phe and Arg, indicated by m/z = 1,015). The presence of [Asp(3)]-MCYST-LR (microcystin with Leu and Arg, Asp non-methylated, indicated by m/z 981), and [Asp(3)]-MCYST-YR (microcystin with Tyr and Arg, Asp non-methylated, indicated by m/z 1,031) were likely. The relative amounts of the peptides varied between February, April, and May. Whole cell extracts from the bloom material revealed specific enzyme inhibitory activities. The serin-proteases trypsin, plasmin, elastase were inhibited, assumable due to the cyanopeptolins found. Elastase and the cysteine-protease papain were not inhibited, inhibitions of protein kinase and glutathione S-transferase (GST) were low. Strong inhibition was observed with protein-phosphatase-1, likely due to the microcystins present in the samples.

Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni

Directory of Open Access Journals (Sweden)

Yadollah Bahrami

2015-01-01

Full Text Available Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core, and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins.

Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination.

Science.gov (United States)

Alkholifi, Faisal K; Albers, David S

2015-10-05

There is accumulating evidence that supports the involvement of reactive oxygen species (ROS), mitochondrial dysfunction and inflammation in the pathogenesis of neurodegenerative diseases. Thus, it is plausible that a multi-targeted therapeutic approach may be a more effective strategy to retard or even potentially halt the progression of the disease. Taurine is an organic acid that has a role in the regulation of oxidative stress and promoting mitochondrial normal functions, and N-Acetyl cysteine (NAC) is a well-known anti-oxidant and glutathione precursor. The main purpose of this study was to examine the cytoprotective effects of taurine alone or in combination with NAC against rotenone-induced toxicity in the SH-SY5Y neuroblastoma cell line. Taurine treatment produced a concentration-dependent reduction in rotenone-induced cell death. From this, we tested sub-effective concentrations of taurine in combination with low, sub-effective concentrations of NAC against rotenone toxicity, and found the combined treatment afforded greater cytoprotection than either treatment alone. The combined taurine/NAC treatment also attenuated rotenone-induced reductions in aconitase activity suggesting the cytoprotection afforded by the combined treatment may be associated with anti-oxidative mechanisms. Together, our data suggest that a multi-targeted approach may yield new avenues of research exploring the utility of combining therapeutic agents with different mechanisms of actions at concentrations lower than previously tested and shown to be cytoprotective. Copyright © 2015 Elsevier B.V. All rights reserved.

N-acetyl Aspartate Levels in Adolescents With Bipolar and/or Cannabis Use Disorders

Science.gov (United States)

Bitter, Samantha M.; Weber, Wade A.; Chu, Wen-Jang; Adler, Caleb M.; Eliassen, James C.; Strakowski, Stephen M.; DelBello, Melissa P.

2014-01-01

Objective Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among: adolescents with bipolar disorder (bipolar group; n=14), adolescents with a cannabis use disorder (cannabis use group, n=13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group, n=25), and healthy adolescents (healthy controls, n=15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups, and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups. Methods N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using Proton Magnetic Resonance Spectroscopy. Results Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post-hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p=0.0002 and p=0.0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations. Conclusions Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder. PMID:24729763

Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

International Nuclear Information System (INIS)

Bame, K.J.

1986-01-01

Acetyl-CoA:α-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal α-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The binding of acetyl-CoA to the enzyme is measured by exchange label from [ 3 H]CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with [ 3 H]acetyl-CoA. The acetyl group can be transferred to glucosamine, forming [ 3 H]N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism

Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast

Directory of Open Access Journals (Sweden)

Kozmin Stanislav G

2005-06-01

Full Text Available Abstract Background N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP and 2-amino-6-hydroxylaminopurine (AHA, are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast. Results We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism. Conclusion We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA.

Synthesis of some glycoside analogs and related compounds from 9-amino-6-(methylthio)-9H-purine.

Science.gov (United States)

Temple, C; Kussner, C L; Montgomery, J A

1975-12-01

Additional information on the anticancer activity of 9-amino-9H-purine-6(1H)-thione and its derivatives was sought by the synthesis of some 9-(substituted amino)-6-(methylthio)-9H-purines in which the 9-substituent contained functional groups capable of either reversible or irreversible binding with an enzymatic site. Condensation of 9-amino-6-(methylthio)-9H-purine (1) with some carbonyl compounds followed by hydride reduction of the azomethine linkage in the intermediates leads to the 2-pyrrolylmethyl (8), 2,3,4-trihydroxybutyl (10), and the 1,5-dihydroxy-2- and 3-pentyl (11 and 12) compounds. A 4-hydroxybutyl derivative (13) was obtained by alkylation of 18, the 9-acetyl derivative of 1, with 4-chlorobutyl acetate followed by saponification. The cyclization of 13 and 11 with a sulfonyl chloride gave the 9-pyrrolidin-1-yl (27) and the 9-[2-(tosyloxymethyl)pyrrolidin-1-yl] (28), respectively. Acylation of 1 with ethyl L-2-pyrrolidine-5-carboxylate and ethyl 1-methyl-5-pyrrolidone-3-carboxylate, respectively, in Me2SO containing NaH gave the corresponding amides 15 and 17. Alkylation of 18 with 1-bromo-2-chloroethane and epichlorohydrin gave the N-(2-chloroethyl) and N-(1,2-epoxy-3-propyl) derivatives 19 and 20. The chloro group of the chlorobutyl derivative of 18 was displaced with KSCN and NaN3, respectively, to give the thiocyanate and azido derivatives 23 and 24. Hydrogenation of the latter gave the amine (25), which was acylated with ethyl chloroformate to give the (ethoxycarbonyl)amino compound 26. None of these compounds showed activity against L1210 leukemia cells implanted ip in mice on a single-dose schedule, suggesting that the activity observed in the simpler 9-aminopurines resulted from cleavage of the hydrazino linkage to give pH-purine-6(1H)-thione.

Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

DEFF Research Database (Denmark)

Savelyeva, I.; Dobbelstein, M.

2011-01-01

to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

Utilization by the isolated perfused rat liver of N-acetyl-D-(1-/sup 14/C)galactosamine and N-brace/sup 3/H)-acetyl-D-galactosamine for the biosynthesis of glycoproteins

Energy Technology Data Exchange (ETDEWEB)

MacNicoll, A D; Wusteman, F S; Powell, G M; Curtis, C G [University Coll., Cardiff (UK)

1978-08-15

The isolated perfused rat liver system has been used to monitor the utilization of N-(/sup 3/H)acetyl-D-galactosamine and N-acetyl-D-(1-/sup 14/C)galactosamine for the biosynthesis of radiolabeled glycoproteins, which are subsequently secreted into the plasma. Both radiolabels appear in a number of different glycoproteins, predominantly as sialic acid and N-acetylglucosamine. The ratio of labelled sialic acid to labelled N-acetylglucosamine varies for different glycoproteins, but the bulk of N-acetyl-D-galactosamine is incorporated without deacetylation.

Acetyl Phosphate as a Primordial Energy Currency at the Origin of Life

Science.gov (United States)

Whicher, Alexandra; Camprubi, Eloi; Pinna, Silvana; Herschy, Barry; Lane, Nick

2018-03-01

Metabolism is primed through the formation of thioesters via acetyl CoA and the phosphorylation of substrates by ATP. Prebiotic equivalents such as methyl thioacetate and acetyl phosphate have been proposed to catalyse analogous reactions at the origin of life, but their propensity to hydrolyse challenges this view. Here we show that acetyl phosphate (AcP) can be synthesised in water within minutes from thioacetate (but not methyl thioacetate) under ambient conditions. AcP is stable over hours, depending on temperature, pH and cation content, giving it an ideal poise between stability and reactivity. We show that AcP can phosphorylate nucleotide precursors such as ribose to ribose-5-phosphate and adenosine to adenosine monophosphate, at modest ( 2%) yield in water, and at a range of pH. AcP can also phosphorylate ADP to ATP in water over several hours at 50 °C. But AcP did not promote polymerization of either glycine or AMP. The amino group of glycine was preferentially acetylated by AcP, especially at alkaline pH, hindering the formation of polypeptides. AMP formed small stacks of up to 7 monomers, but these did not polymerise in the presence of AcP in aqueous solution. We conclude that AcP can phosphorylate biologically meaningful substrates in a manner analogous to ATP, promoting the origins of metabolism, but is unlikely to have driven polymerization of macromolecules such as polypeptides or RNA in free solution. This is consistent with the idea that a period of monomer (cofactor) catalysis preceded the emergence of polymeric enzymes or ribozymes at the origin of life.

Hydroxychavicol: a new anti-nitrosating phenolic compound from betel leaf.

Science.gov (United States)

Nagabhushan, M; Amonkar, A J; Nair, U J; D'Souza, A V; Bhide, S V

1989-05-01

Hydroxychavicol and eugenol are the phenolic compounds isolated from betel leaf (piper betel). The modulation of nitrosation of methylurea by sodium nitrite at pH 3.6 and 30 degrees C was studied. The formation of mutagenic N-nitrosomethylurea was monitored by checking the mutagenicity of reaction mixture in Salmonella typhimurium strain TA100 and TA1535 without S9 mix. Hydroxychavicol and eugenol exhibit dose-dependent suppression of nitrosation in vitro without affecting the survival of the bacteria. Pre- or post-treatment of bacterial cells from S. typhimurium strains TA100 and TA1535 with phenolics did not modify the mutagenicity of nitrosomethylurea. The blocking of hydroxy group(s) in the benzene ring by acetylation abolishes the anti-nitrosating activity of the molecule(s). The nitrosation inhibition by hydroxychavicol is through scavenging of nitrite ions in the media, thus making them non-available for the nitrosation of methylurea.

The chemical nature of phenolic compounds determines their toxicity and induces distinct physiological responses in Saccharomyces cerevisiae in lignocellulose hydrolysates

Science.gov (United States)

2014-01-01

We investigated the severity of the inhibitory effects of 13 phenolic compounds usually found in spruce hydrolysates (4-hydroxy-3-methoxycinnamaldehyde, homovanilyl alcohol, vanillin, syringic acid, vanillic acid, gallic acid, dihydroferulic acid, p-coumaric acid, hydroquinone, ferulic acid, homovanillic acid, 4-hydroxybenzoic acid and vanillylidenacetone). The effects of the selected compounds on cell growth, biomass yield and ethanol yield were studied and the toxic concentration threshold was defined for each compound. Using Ethanol Red, the popular industrial strain of Saccharomyces cerevisiae, we found the most toxic compound to be 4-hydroxy-3-methoxycinnamaldehyde which inhibited growth at a concentration of 1.8 mM. We also observed that toxicity did not generally follow a trend based on the aldehyde, acid, ketone or alcohol classification of phenolic compounds, but rather that other structural properties such as additional functional groups attached to the compound may determine its toxicity. Three distinctive growth patterns that effectively clustered all the compounds involved in the screening into three categories. We suggest that the compounds have different cellular targets, and that. We suggest that the compounds have different cellular targets and inhibitory mechanisms in the cells, also compounds who share similar pattern on cell growth may have similar inhibitory effect and mechanisms of inhibition. PMID:24949277

Efficient acetylation of primary amines and amino acids in ...

Indian Academy of Sciences (India)

This effort represents the first efficient use of this most reactive but cheap acetylating agent to acetylate amines in excellent yields in aqueous medium. This is a potentially useful green chemical transformation where reaction takes place in environment-friendly brine solution leading to easy work-up and isolation of the ...

Specific lysosomal transport of small neutral amino acids

International Nuclear Information System (INIS)

Pisoni, R.L.; Flickinger, K.S.; Thoene, J.G.; Christensen, H.N.

1986-01-01

Studies of amino acid exodus from lysosomes have allowed us previously to describe transport systems specific for cystine and another for cationic amino acids in fibroblast lysosomes. They are now able to study amino acid uptake into highly purified fibroblast lysosomes obtained by separating crude granular fraction on gradients formed by centrifugation in 35% isoosmotic Percoll solutions. Analog inhibition and saturation studies indicate that L-[ 14 C]proline (50 μM) uptake by fibroblast lysosomes at 37 0 C in 50 mM citrate/tris pH 7.0 buffer containing 0.25 M sucrose is mediated by two transport systems, one largely specific for L-proline and the other for which transport is shared with small neutral amino acids such as alanine, serine and threonine. At 7 mM, L-proline inhibits L-[ 14 C]proline uptake almost completely, whereas ala, ser, val, thr, gly, N-methylalanine and sarcosine inhibit proline uptake by 50-65%. The system shared by alanine, serine and threonine is further characterized by these amino acids strongly inhibiting the uptakes of each other. Lysosomal proline transport is selective for the L-isomer of the amino acid, and is scarcely inhibited by 7 mM arg, glu, asp, leu, phe, his, met, (methylamino) isobutyrate, betaine or N,N-dimethylglycine. Cis or trans-4-hydroxy-L-proline inhibit proline uptake only slightly. In sharp contrast to the fibroblast plasma membrane in which Na + is required for most proline and alanine transport, lysosomal uptake of these amino acids occurs independently of Na +

N-acetylation and phosphorylation of Sec complex subunits in the ER membrane

Directory of Open Access Journals (Sweden)

Soromani Christina

2012-12-01

Full Text Available Abstract Background Covalent modifications of proteins provide a mechanism to control protein function. Here, we have investigated modifications of the heptameric Sec complex which is responsible for post-translational protein import into the endoplasmic reticulum (ER. It consists of the Sec61 complex (Sec61p, Sbh1p, Sss1p which on its own mediates cotranslational protein import into the ER and the Sec63 complex (Sec63p, Sec62p, Sec71p, Sec72p. Little is known about the biogenesis and regulation of individual Sec complex subunits. Results We show that Sbh1p when it is part of the Sec61 complex is phosphorylated on T5 which is flanked by proline residues. The phosphorylation site is conserved in mammalian Sec61ß, but only partially in birds, and not in other vertebrates or unicellular eukaryotes, suggesting convergent evolution. Mutation of T5 to A did not affect the ability of mutant Sbh1p to complement the growth defect in a Δsbh1Δsbh2 strain, and did not result in a hypophosphorylated protein which shows that alternate sites can be used by the T5 kinase. A survey of yeast phosphoproteome data shows that Sbh1p can be phosphorylated on multiple sites which are organized in two patches, one at the N-terminus of its cytosolic domain, the other proximal to the transmembrane domain. Surprisingly, although N-acetylation has been shown to interfere with ER targeting, we found that both Sbh1p and Sec62p are cotranslationally N-acetylated by NatA, and N-acetyl-proteome data indicate that Sec61p is modified by the same enzyme. Mutation of the N-acetylation site, however, did not affect Sec62p function in posttranslational protein import into the ER. Disabling NatA resulted in growth retardation, but not in co- or posttranslational translocation defects or instability of Sec62p or Sbh1p. Conclusions We conclude that N-acetylation of transmembrane and tail-anchored proteins does not interfere with their ER-targeting, and that Sbh1p phosphorylation on T5

The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

Directory of Open Access Journals (Sweden)

Sang Il Gum

2013-01-01

Full Text Available Previously, we found that Korean red ginseng suppressed acetaminophen (APAP-induced hepatotoxicity via alteration of its metabolic profile involving GSTA2 induction and that ginsenoside Rg3 was a major component of this gene induction. In the present study, therefore, we assessed the protective effect of Rg3 against N-acetyl-p-benzoquinone imine (NAPQI, a toxic metabolic intermediate of APAP. Excess NAPQI resulted in GSH depletion with increases in the ALT and AST activities in H4IIE cells. Rg3 pretreatment reversed GSH depletion by NAPQI. Rg3 resulted in increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase (GCL, the rate-limiting steps in GSH synthesis and subsequently increased GSH content. Rg3 increased levels of nuclear Nrf2, an essential transcriptional factor of these genes. The knockdown or knockout of the Nrf2 gene abrogated the inductions of mRNA and protein by Rg3. Abolishment of the reversal of GSH depletion by Rg3 against NAPQI was observed in Nrf2-deficient cells. Rg3 induced multidrug resistance-associated protein (Mrp 1 and Mrp3 mRNA levels, but not in Nrf2-deficient cells. Taken together, these results demonstrate that Rg3 is efficacious in protecting hepatocytes against NAPQI insult, due to GSH repletion and coordinated gene regulations of GSH synthesis and Mrp family genes by Nrf2.

Amino sugars in suspended particulate matter from the Bay of Bengal during the summer monsoon of 2001

Digital Repository Service at National Institute of Oceanography (India)

Fernandes, L.; De; Matondkar, S.G.P.; Bhosle, N.B.

and pseudopeptidoglycan (Brock et al 1994). AS are also important con- stituents of many biopolymers such as polysac- charides, glycoproteins and glycolipids (Sharon 1965). Moreover, chitin, a polymer of amino sugar, N-acetyl glucosamine (Muzzarelli 1977; Benner.../F glass fibre filters (0.7?m pore size) for the analysis of particu- late organic carbon (POC), particulate nitrogen (PN) and amino sugars (AS) concentration and composition. 2.3 Analysis of samples The SPM samples were de-carbonated overnight using fuming...

Response of nitrogen metabolism to boron toxicity in tomato plants.

Science.gov (United States)

Cervilla, L M; Blasco, B; Ríos, J J; Rosales, M A; Rubio-Wilhelmi, M M; Sánchez-Rodríguez, E; Romero, L; Ruiz, J M

2009-09-01

Boron (B) toxicity has become important in areas close to the Mediterranean Sea where intensive agriculture has been developed. The objective of this research was to study the effects of B toxicity (0.5 mM and 2.0 mM B) on nitrogen (N) assimilation of two tomato cultivars that are often used in these areas. Leaf biomass, relative leaf growth rate (RGR(L)), concentration of B, nitrate (NO(3) (-)), ammonium (NH(4) (+)), organic N, amino acids and soluble proteins, as well as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthase (GS), glutamate synthetase (GOGAT) and glutamate dehydrogenase (GDH) activities were analysed in leaves. Boron toxicity significantly decreased leaf biomass, RGR(L), organic N, soluble proteins, and NR and NiR activities. The lowest NO(3) (-) and NH(4) (+) concentration in leaves was recorded when plants were supplied with 2.0 mM B in the root medium. Total B, amino acids, activities of GS, GOGAT and GDH increased under B toxicity. Data from the present study prove that B toxicity causes inhibition of NO(3) (-) reduction and increases NH(4) (+) assimilation in tomato plants.

Structural studies on 4-O-acetyl-α-N-acetylneuraminyl-(2→3)-lactose, the main oligosaccharide in echidna milk

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Kamerling, J.P.; Dorland, L.; Halbeek, H. van; Messer, M.; Schauer, R.

1982-01-01

The main oligosaccharide (50%) in the milk of the Australian echidna (Tachyglossus aculeatus) has been identified unequivocally as 4-O-acetyl-α-N-acetylneur-aminyl-(2→3)-lactose. The 4-O-acetyl substituent of the sialic acid residue was characterised by g.l.c.-m.s. of the isolated (after mild, acid

The effect of N-acetylated DL-penicillamin and DL-homocysteine thiolactone on the mercury distribution in adult rats, rat foetuses and macaca monkeys after exposure to methyl mercuric chloride

International Nuclear Information System (INIS)

Aaseth, J.; Wannag, A.; Norseth, T.; Institute of Occupational Health, Oslo, Norway)

1976-01-01

The distribution and excretion of mercury was studied in pregnant rats, given a single intravenous dose of 2 μmol/kg of CH 3 203 HgCl on the 13th day of pregnancy. Oral treatment for one week with N-acetyl-DL-penicillamine (4 mmol/kg per day) increased the mercury excretion in faces (from 45 to 120 nmol) and urine (from 9 to 160 nmol). Such treatment mobilized mercury from all the organs tested and the foetal and maternal brain levels of mercury were decreased to 1/5 and 1/3 of the controls, respectively. A four-day period of treatment with N-acetyl-DL-penicillamine started three days after the injection of methyl mercury reduced the foetal and maternal brain levels to 1/2 and 2/3 of the controls, respectively. The rapid removal of metal deposits following treatment with N-acetyl-DL-penicillamine is attributed to a free penetration of the complexing thiol into the tissue cells in question. No signs of toxicity were detected in monkeys given an effective daily dose of the agent (4 mmol/kg) for 6 days. In contrast N-acetyl-DL-homocysteine thiolactone was found to be toxic in the monkeys. In addition, the latter agent was ineffective in increasing the mercury elimination from the brains of monkeys, rats and rat foetuses. (author)

Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

International Nuclear Information System (INIS)

Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang Luoping

2009-01-01

Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As III ). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As III through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As III and to its more toxic metabolite monomethylarsonous acid (MMA III ) at doses relevant to high environmental human exposures. In addition, both As III and MMA III treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

Synthesis and in vitro toxicity of new dodecaborate-containing amino acids

International Nuclear Information System (INIS)

Slepukhina, Irina; Gabel, Detlef

2006-01-01

Two unnatural, boron-containing amino acids were synthesized by alkylation of S-(2-cyanoethyl)-thio-undecahydro-closo-dodecaborate(2-). S-(2-amino-2-carboxylpropyl)-thio-undecahydro-closo-dodecaborate (2-), containing a quaternary carbon atom, and O-(5-amino-5-carboxylpentyl)-oxy-undecahydro-closo-dodecaborate(2-) were evaluated for in vitro toxicity using V 79 Chinese hamster cells. (author)

Testing the toxicity of metals, phenol, effluents, and receiving waters by root elongation in Lactuca sativa L.

Science.gov (United States)

Lyu, Jie; Park, Jihae; Kumar Pandey, Lalit; Choi, Soyeon; Lee, Hojun; De Saeger, Jonas; Depuydt, Stephen; Han, Taejun

2018-03-01

Phytotoxicity tests using higher plants are among the most simple, sensitive, and cost-effective of the methods available for ecotoxicity testing. In the present study, a hydroponic-based phytotoxicity test using seeds of Lactuca sativa was used to evaluate the water quality of receiving waters and effluents near two industrial sites (Soyo and Daejon) in Korea with respect to the toxicity of 10 metals (As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, Zn) and phenol, and of the receiving waters and effluents themselves. First, the L. sativa hydroponic bioassay was used to determine whether the receiving water or effluents were toxic; then, the responsible toxicant was identified. The results obtained with the L. sativa bioassay ranked the EC 50 toxicities of the investigated metal ions and phenol as: Cd > Ni > Cu > Zn > Hg > phenol > As > Mn > Cr > Pb > Fe. We found that Zn was the toxicant principally responsible for toxicity in Daejeon effluents. The Daejeon field effluent had a higher Zn concentration than permitted by the effluent discharge criteria of the Ministry of Environment of Korea. Our conclusion on the importance of Zn toxicity was supported by the results of the L. sativa hydroponic assay, which showed that the concentration of Zn required to inhibit root elongation in L. sativa by 50% (EC 50 ) was higher in the Daejeon field effluent than that of pure Zn. More importantly, we proved that the L. sativa hydroponic test method can be applied not only as an alternative tool for determining whether a given waste is acceptable for discharge into public water bodies, but also as an alternative method for measuring the safety of aquatic environments using EC 20 values, with respect to the water pollutants investigated (i.e., Cd, Cr, Cu, Pb, Mn, Hg, Ni, Zn, and phenol). Copyright © 2017. Published by Elsevier Inc.

Selenite modulates the level of phenolics and nutrient element to alleviate the toxicity of arsenite in rice (Oryza sativa L.).

Science.gov (United States)

Chauhan, Reshu; Awasthi, Surabhi; Tripathi, Preeti; Mishra, Seema; Dwivedi, Sanjay; Niranjan, Abhishek; Mallick, Shekhar; Tripathi, Pratibha; Pande, Veena; Tripathi, Rudra Deo

2017-04-01

Arsenic (As) contamination of paddy rice is a serious threat all over the world particularly in South East Asia. Selenium (Se) plays important role in protection of plants against various abiotic stresses including heavy metals. Moreover, arsenite (AsIII) and selenite (SeIV) can be biologically antagonistic due to similar electronic configuration and sharing the common transporter for their uptake in plant. In the present study, the response of oxidative stress, phenolic compounds and nutrient elements was analyzed to investigate Se mediated As tolerance in rice seedlings during AsIII and SeIV exposure in hydroponics. Selenite (25µM) significantly decreased As accumulation in plant than As (25µM) alone treated plants. Level of oxidative stress related parameters viz., reactive oxygen species (ROS), lipid peroxidation, electrical conductivity, nitric oxide and pro-oxidant enzyme (NADPH oxidase), were in the order of As>As+Se>control>Se. Selenium ameliorated As phytotoxicity by increased level of phenolic compounds particularly gallic acid, protocatechuic acid, ferulic acid and rutin and thiol metabolism related enzymes viz., serine acetyl transferase (SAT) and cysteine synthase (CS). Selenium supplementation enhanced the uptake of nutrient elements viz., Fe, Mn, Co, Cu, Zn, Mo, and improved plant growth. The results concluded that Se addition in As contaminated environment might be an important strategy to reduce As uptake and associated phytotoxicity in rice plant by modulation of phenolic compounds and increased uptake of nutrient elements. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhibition of translation by 7-methyl guanosine (m7G) nucleotide cap analogs with derivatized 5'-monophosphates

International Nuclear Information System (INIS)

Tahara, S.M.; Darzynkiewicz, E.; Ekiel, I.

1986-01-01

Recognition of the 5'-m 7 GpppN (cap) structure of eukaryote mRNA is an important step of translation initiation as shown by the potent inhibitory effect of m 7 G nucleotides on this process. A comparison of cap analogs as competitive inhibitors of initiation has allowed the authors to map probable protein-ligand contact points between the cap and cognate cap binding proteins (CBPs). Recently, several new derivatives of m 7 GMP (1) with modified phosphates were synthesized: m 7 G 5'-phosphite (2), m 7 G 5'-phosphoramidate (3), m 7 G 5'-methylphosphonate (4), and m 7 G 5'-phosphate-O-methyl ester (5). In addition, 7,8-dimethyl GMP (6) and 7-methyl 8-amino GMP (7) were synthesized. 6 and7 are primarily syn and anti respectively, relative to the glycosidic bond as shown by solution NMR studies. Inhibition by analogs on total translation in reticulocyte lysate and binding of mRNA to rabbit reticulocyte ribosomes was found to be: 1 = 3 > 5 > 4 > 2. The inhibitory activity of 3 was unexpected since it is isosteric with 4, however it suggested that electron configuration and/or the ability to form a hydrogen bond between protein and the phosphate moiety might be important for ligand binding. 7 was more inhibitory than 6. The latter two are isosteric therefore differences in electron delocalization and/or syn-anti conformation are likely to be the reason(s) for the observed difference

Fragrance material review on acetyl cedrene.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Politano, V T; Api, A M

2013-12-01

A toxicologic and dermatologic review of acetyl cedrene when used as a fragrance ingredient is presented. Acetyl cedrene is a member of the fragrance structural group Alkyl Cyclic Ketones. The generic formula for this group can be represented as (R1)(R2)CO. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for acetyl cedrene were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (2013) (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients. Submitted with this manuscript.) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013. Published by Elsevier Ltd.

Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites

Directory of Open Access Journals (Sweden)

Hotta C.T.

2003-01-01

Full Text Available The duration of the intraerythrocytic cycle of Plasmodium is a key factor in the pathogenicity of this parasite. The simultaneous attack of the host red blood cells by the parasites depends on the synchronicity of their development. Unraveling the signals at the basis of this synchronicity represents a challenging biological question and may be very important to develop alternative strategies for therapeutic approaches. Recently, we reported that the synchrony of Plasmodium is modulated by melatonin, a host hormone that is synthesized only during the dark phases. Here we report that N-acetyl-serotonin, a melatonin precursor, also releases Ca2+ from isolated P. chabaudi parasites at micro- and nanomolar concentrations and that the release is blocked by 250 mM luzindole, an antagonist of melatonin receptors, and 20 mM U73122, a phospholipase C inhibitor. On the basis of confocal microscopy, we also report the ability of 0.1 µM melatonin and 0.1 µM N-acetyl-serotonin to cross the red blood cell membrane and to mobilize intracellular calcium in parasites previously loaded with the fluorescent calcium indicator Fluo-3 AM. The present data represent a step forward into the understanding of the signal transduction process in the host-parasite relationship by supporting the idea that the host hormone melatonin and N-acetyl-serotonin generate IP3 and therefore mobilize intracellular Ca2+ in Plasmodium inside red blood cells.

Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells.

Science.gov (United States)

Banijamali, Mahsan; Rabbani-Chadegani, Azra; Shahhoseini, Maryam

2016-07-01

Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Phylogenetic diversity of bacteria associated with toxic and non-toxic ...

African Journals Online (AJOL)

Phylogenetic diversity of bacteria associated with toxic and non-toxic strains of Alexandrium minutum. L Palacios, B Reguera, J Franco, I Marín. Abstract. Marine planktonic dinoflagellates are usually associated with bacteria, some of which seem to have a symbiotic relation with the dinoflagellate cells. The role of bacteria in ...

The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants

DEFF Research Database (Denmark)

Behrendt, N; Rønne, E; Ploug, M

1990-01-01

-PA. The purified protein shows a single 55-60 kDa band after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. It is a heavily glycosylated protein, the deglycosylated polypeptide chain comprising only 35 kDa. The glycosylated protein contains N-acetyl-D-glucosamine and sialic acid......, but no N-acetyl-D-galactosamine. Glycosylation is responsible for substantial heterogeneity in the receptor on phorbol ester-stimulated U937 cells, and also for molecular weight variations among various cell lines. The amino acid composition and the NH2-terminal amino acid sequence are reported...

Mechanistic studies on the conjugation of methyl isocyanate with N-Acetyl-Cysteine in rats

International Nuclear Information System (INIS)

Hu, P.; Davis, M.R.; Baillie, T.A.

1996-01-01

In order to investigate the utility of selected thiols as scavengers of MIC, we first assessed the chemical stability of SMG, AMCC and SMC by measuring their rates of reaction in vitro with thiorphan. The initial rates of carbamoylation of thiorpan (0.5 mM) by the above conjugates (0.5 mM) in aqeous buffer at pH 7.4 and 37 deg C were 2.51, 0.76 and 8.47 μmol L -1 min -1 , repectively, indicating that the mercapturate AMCC was the most stable of the three MIC conjugates. In light of these results, studies were conducted to examine the effect of pretreatment with N-acetyl-L-cysteine (L-NAC; 500 mg kg -1 , i.p.) on the urinary elimination of AMCC in rats dosed with MIC (15 mg kg -1 , i.p.). In separate experiments, groups of rats were pretreated with either N-acetyl-D-cysteine (D-NAC) or N-trideuteroacetyl-L-cysteine (d 3 -L-NAC) in order to explore the mechanism by which MIC undergoes conjugation to AMCC in vivo. The results indicated that exogenous NAC effectively enhancess the urinary excretion of MIC in the form of AMCC, and that it does so lagerly by direct conjugation with the isocyanate, rather than via biosynthesis to GSH. (author). 9 refs., 5 figs

Production of Nα-acetyl Tα1-HSA through in vitro acetylation by RimJ.

Science.gov (United States)

Chen, Jing; Li, Haibin; Wang, Tao; Sun, Shuyang; Liu, Jia; Chen, Jianhua

2017-11-10

Thymosin alpha 1 (Tα1) is an important immunomodulating agent with various clinical applications. The natural form of Tα1 is N α -acetylated, which was supposed to be related to in vivo stability of the hormone. In this study, fusion protein Tα1-HSA was constructed and expressed in Pichia pastoris . RimJ, a N α -acetyltransferase from E.coli , was also overexpressed and purified to homogeneity. In vitro acetylation of Tα1-HSA in the presence of RimJ and acetyl coenzyme A resulted in N α -acetyl Tα1-HSA. The N α -acetylation was determined by LC-MS/MS. Kinetic assay indicated that RimJ had a higher affinity to desacetyl Tα1 than to Tα1-HSA. Bioactivity assay revealed fully retained activity of Tα1 when the hormone was connected to the N-terminus of the fusion protein, while the activity was compromised in our previously constructed HSA-Tα1. With fully retained activity and N-terminal acetylation, N α -acetyl Tα1-HSA was expected to be a more promising pharmaceutical agent than Tα1.

Toxicity of nickel and silver to Nostoc muscorum: interaction with ascorbic acid, glutathione, and sulfur-containing amino acids.

Science.gov (United States)

Rai, L C; Raizada, M

1987-08-01

Exposure of Nostoc muscorum to different concentrations of Ni and Ag brought about reduction in growth, carbon fixation, heterocyst production, and nitrogenase activity and increase in the loss of ions (K+, Na+). In an attempt to ameliorate the toxicity of test metals by ascorbic acid, glutathione, and sulfur-containing amino acids (L-cysteine and L-methionine), it was found that the level of protection by ascorbic acid and glutathione was more for Ag than Ni. However, metal-induced inhibition of growth and carbon fixation was equally ameliorated by methionine. But the level of protection by cysteine was quite different, i.e., 27% for Ni and 22% for Ag. Protection of metal toxicity in N. muscorum by amino acids lends further support to self-detoxifying ability of cyanobacteria because they are known to synthesize all essential amino acids.

Kinetics of the transformation of n-propyl gallate and structural analogs in the perfused rat liver

International Nuclear Information System (INIS)

Eler, Gabrielle Jacklin; Santos, Israel Souza; Giaretta de Moraes, Amarilis; Mito, Márcio Shigueaki; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

2013-01-01

n-Propyl gallate and its analogs are used in foods and other products to prevent oxidation. In the liver the compound exerts several harmful effects, especially gluconeogenesis inhibition. The mode of transport and distribution of n-propyl gallate and its kinetics of biotransformation have not yet been investigated. To fill this gap the transformation, transport and distribution of n-propyl gallate and two analogs were investigated in the rat liver. Isolated perfused rat liver was used. n-Propyl gallate, methyl gallate, n-octyl gallate and transformation products were quantified by high pressure-liquid chromatography coupled to fluorescence detection. The interactions of n-propyl gallate and analogs with the liver presented three main characteristics: (1) the hydrolytic release of gallic acid from n-propyl gallate and methyl gallate was very fast compared with the subsequent transformations of the gallic acid moiety; (2) transport of the esters was very fast and flow-limited in contrast to the slow and barrier-limited transport of gallic acid; (3) the apparent distribution volume of n-propyl gallate, but probably also of methyl gallate and n-octyl gallate, greatly exceeded the water space in the liver, contrary to the gallic acid space which is smaller than the water space. It can be concluded that at low portal concentrations (< 50 μM) the gallic acid esters are 100% extracted during a single passage through the liver, releasing mainly gallic acid into the systemic circulation. For the latter a considerable time is required until complete biotransformation. The exposure of the liver to the esters, however, is quite prolonged due to extensive intracellular binding. - Highlights: • The liver binds very strongly n-propyl gallate and releases basically gallic acid. • n-propyl gallate and analogs undergo concentrative flow-limited distribution. • Gallic acid undergoes barrier-limited distribution and is slowly transformed. • The long residence time of n

Kinetics of the transformation of n-propyl gallate and structural analogs in the perfused rat liver

Energy Technology Data Exchange (ETDEWEB)

Eler, Gabrielle Jacklin; Santos, Israel Souza; Giaretta de Moraes, Amarilis; Mito, Márcio Shigueaki; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar, E-mail: adebracht@uol.com.br

2013-11-15

n-Propyl gallate and its analogs are used in foods and other products to prevent oxidation. In the liver the compound exerts several harmful effects, especially gluconeogenesis inhibition. The mode of transport and distribution of n-propyl gallate and its kinetics of biotransformation have not yet been investigated. To fill this gap the transformation, transport and distribution of n-propyl gallate and two analogs were investigated in the rat liver. Isolated perfused rat liver was used. n-Propyl gallate, methyl gallate, n-octyl gallate and transformation products were quantified by high pressure-liquid chromatography coupled to fluorescence detection. The interactions of n-propyl gallate and analogs with the liver presented three main characteristics: (1) the hydrolytic release of gallic acid from n-propyl gallate and methyl gallate was very fast compared with the subsequent transformations of the gallic acid moiety; (2) transport of the esters was very fast and flow-limited in contrast to the slow and barrier-limited transport of gallic acid; (3) the apparent distribution volume of n-propyl gallate, but probably also of methyl gallate and n-octyl gallate, greatly exceeded the water space in the liver, contrary to the gallic acid space which is smaller than the water space. It can be concluded that at low portal concentrations (< 50 μM) the gallic acid esters are 100% extracted during a single passage through the liver, releasing mainly gallic acid into the systemic circulation. For the latter a considerable time is required until complete biotransformation. The exposure of the liver to the esters, however, is quite prolonged due to extensive intracellular binding. - Highlights: • The liver binds very strongly n-propyl gallate and releases basically gallic acid. • n-propyl gallate and analogs undergo concentrative flow-limited distribution. • Gallic acid undergoes barrier-limited distribution and is slowly transformed. • The long residence time of n

Topical effects of N-acetyl-L-hydroxyproline on ceramide synthesis and alleviation of pruritus

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Hashizume E

2013-02-01

Full Text Available Erika Hashizume,1 Tetsuo Nakano,2 Ayako Kamimura,1 Koji Morishita31Healthcare Products Development Center, Kyowa Hakko Bio, Tsukuba, Ibaraki, 2Technical Research Laboratories, Kyowa Hakko Bio, Hofu, Yamaguchi, 3Technology Development and Research Department, Kyowa Hakko Bio, Tokyo, JapanPurpose: N-acetyl-l-hydroxyproline (AHYP is an acetylated form of l-hydroxyproline that is used to treat skin ulcers and porphyria cutanea tarda. Its other biological and physiological effects on the skin have not been elucidated. We investigated the effects of AHYP on the skin-barrier function, focusing on ceramide synthesis and the effects of topical AHYP on atopic dermatitis.Materials and methods: AHYP was applied to a three-dimensional cultured skin model. Ceramides were quantified by high-performance thin-layer chromatography. Serine palmitoyltransferase (SPT is the rate-limiting enzyme in de novo ceramide synthesis, and the mRNA of its long-chain base subunit 1 (SPTLC1 was evaluated by quantitative reverse-transcription polymerase chain reaction. A clinical trial in the form of an intraindividual, comparative, double-blind, randomized, vehicle-controlled test involving 15 female subjects suffering from slight atopic dermatitis was performed. Subjects applied 1% (w/w AHYP cream to one forearm and a control cream to the other forearm twice daily for 4 weeks. Skin condition was evaluated by measuring transepidermal water loss (TEWL. Dermatological observations were made by a dermatologist, and subjects evaluated their own pruritus intensity before beginning treatment and 4 weeks after the start of treatment.Results: SPTLC1 expression and ceramide synthesis were significantly increased in an AHYP-treated skin model (P < 0.05. In the clinical trial, no adverse effects were observed in any subjects. TEWL was increased in the control-treated region of the forearm (P < 0.05 after 4 weeks' application, whereas there was no change in the AHYP-treated region of the

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor1[S

OpenAIRE

Zhang, Hao; Jing, Xigang; Shi, Yang; Xu, Hao; Du, Jianhai; Guan, Tongju; Weihrauch, Dorothee; Jones, Deron W.; Wang, Weiling; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

2013-01-01

Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (⩽4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HO...

A non-toxic fluorogenic dye for mitochondria labeling.

Science.gov (United States)

Han, Junyan; Han, Myung Shin; Tung, Ching-Hsuan

2013-11-01

Mitochondria, powerhouses of cells, are responsible for many critical cellular functions, such as cell energy metabolism, reactive oxygen species production, and apoptosis regulation. Monitoring mitochondria morphology in live cells temporally and spatially could help with the understanding of the mechanisms of mitochondrial functional regulation and the pathogenesis of mitochondria-related diseases. A novel non-cytotoxic fluorogenic compound, AcQCy7, was developed as a mitochondria-specific dye. AcQCy7 emitted no fluorescent signal outside of cells, but it became fluorescent after intracellular hydrolysis of the acetyl group. The hydrolyzed fluorescent product was well retained in mitochondria, enabling long-lasting fluorescence imaging of mitochondria without cell washing. A 2-day culture study using AcQCy7 showed no sign of cytotoxicity, whereas a commonly used mitochondria-staining probe, Mitochondria Tracker Green, caused significant cell death even at a much lower concentration. Apoptosis-causing mitochondria fission was monitored clearly in real time by AcQCy7. A simple add-and-read mitochondria specific dye AcQCy7 has been validated in various cell models. Bright mitochondria specific fluorescent signal in treated cells lasted several days without noticeable toxicity. The probe AcQCy7 has been proofed to be a non-toxic agent for long-term mitochondria imaging. © 2013.

Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

KAUST Repository

Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

2015-01-01

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

KAUST Repository

Jin, Peng

2015-10-27

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

Efficient 1H-NMR Quantitation and Investigation of N-Acetyl-D-glucosamine (GlcNAc and N,N'-Diacetylchitobiose (GlcNAc2 from Chitin

Directory of Open Access Journals (Sweden)

Huey-Lang Yang

2011-09-01

Full Text Available A quantitative determination method of N-acetyl-D-glucosamine (GlcNAc and N,N'-diacetylchitobiose (GlcNAc2 is proposed using a proton nuclear magnetic resonance experiment. N-acetyl groups of GlcNAc and (GlcNAc2 are chosen as target signals, and the deconvolution technique is used to determine the concentration of the corresponding compound. Compared to the HPLC method, 1H-NMR spectroscopy is simple and fast. The method can be used for the analysis of chitin hydrolyzed products with real-time analysis, and for quantifying the content of products using internal standards without calibration curves. This method can be used to quickly evaluate chitinase activity. The temperature dependence of 1H-NMR spectra (VT-NMR is studied to monitor the chemical shift variation of acetyl peak. The acetyl groups of products are involved in intramolecular H-bonding with the OH group on anomeric sites. The rotation of the acetyl group is closely related to the intramolecular hydrogen bonding pattern, as suggested by the theoretical data (molecular modeling.

N-Acetyl-L-Leucine Accelerates Vestibular Compensation after Unilateral Labyrinthectomy by Action in the Cerebellum and Thalamus

Science.gov (United States)

Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

2015-01-01

An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus. PMID:25803613

Neutral and stereospecific Tc-99m complexes: [99mTc]N-benzyl-3,4-di-(N-2-mercaptoethyl)-amino-pyrrolidines (P-BAT)

International Nuclear Information System (INIS)

Zhuang Zhiping; Ploessl, Karl; Kung Meiping; Mu Mu; Kung, Hank F.

1999-01-01

Technetium-99m-labeled radiopharmaceuticals are currently the most commonly used agents in nuclear medicine. To prepare binding site-specific small molecules containing a Tc-99m complexing core, it is important to consider a ligand system, which selectively forms only one stereoisomer. A novel series of bisaminoethanethiol (BAT) derivatives as a model system were prepared. Stereoisomers of N-benzyl-3,4-di-(N-2-mercaptoethyl)-amino pyrrolidines (P-BAT): (3R,4R)-P-BAT (R,R-4) and (3,4)meso-P-BAT (8), the trans and meso isomer, respectively, as a chelating group were prepared successfully. The desired Tc-99m P-BAT complexes were obtained by using Sn(II)/glucoheptonate as the reducing agent for [ 99m Tc]pertechnetate. As predicted, after complexation with [ 99m Tc]Tc v O, the trans isomer, (3R,4R)-P-BAT (R,R-4), showed only one isomer; whereas the corresponding meso isomer, (3,4)meso-P-BAT (8), produced two distinctive complexes isolated readily by high performance liquid chromatography (HPLC). The [ 99m Tc](R,S)meso-P-BAT (8) isomers showed a different lipophilicity (partition coefficient [P.C.]=54.3 and 55.4 for peak A and peak B, respectively), as compared with that of the corresponding [ 99m Tc](3R,4R)-P-BAT (R,R-4), trans isomer ( P.C.=163). Results of the biodistribution study in rats of these isomers show different heart and brain uptake, suggesting that the intrinsic differences in biodistribution are due to structural and stereospecific factors. Examples in this report confirm that it is possible to design stereospecific Tc-99m complexes based on the bisaminoethanethiol (N 2 S 2 , BAT) ligand system. Consideration on stereoselectivity of site-specific agents labeled with Tc-99m is likely an essential requirement on developing binding-site specific radiopharmaceuticals

Biomedical Activity of Chitin/Chitosan Based Materials—Influence of Physicochemical Properties Apart from Molecular Weight and Degree of N-Acetylation

Directory of Open Access Journals (Sweden)

Mirko X. Weinhold

2011-11-01

Full Text Available The physicochemical nature of chitin and chitosan, which influences the biomedical activity of these compounds, is strongly related to the source of chitin and the conditions of the chitin/chitosan production process. Apart from widely described key factors such as weight-averaged molecular weight (MW and degree of N-acetylation (DA, other physicochemical parameters like polydispersity (MW/MN, crystallinity or the pattern of acetylation (PA have to be taken into consideration. From the biological point of view, these parameters affect a very important factor—the solubility of chitin and chitosan in water and organic solvents. The physicochemical properties of chitosan solutions can be controlled by manipulating solution conditions (temperature, pH, ionic strength, concentration, solvent. The degree of substitution of the hydroxyl and the amino groups or the degree of quaternization of the amino groups also influence the mechanical and biological properties of chitosan samples. Finally, a considerable research effort has been directed towards developing safe and efficient chitin/chitosan-based products because many factors, like the size of nanoparticles, can determine the biomedical characteristics of medicinal products. The influence of these factors on the biomedical activity of chitin/chitosan-based products is presented in this report in more detail.

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

Directory of Open Access Journals (Sweden)

Tomohiro Osaki

2015-08-01

Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

Structure Activity Relationships of N-linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids

Directory of Open Access Journals (Sweden)

Makanjuola Ogunsina

2013-12-01

Full Text Available 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl-sn-glycerol (1 was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice and was inactive against breast tumor xenografts in mice. This inactivity was attributed to hydrolysis of the glycosidic linkage by glycosidases. Here three N-linked (glycosylamide analogs 2–4, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and 7 with different stereochemistry at the C2-position of the glycerol moiety were synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB-231, pancreas (MiaPaCa2 and prostrate (DU145, PC3 cancer cell lines was determined. The diglycosylated analogs 1-O-hexadecyl-2(R-, 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl-sn-glycerol (7 and the 1:1 diastereomeric mixture of 1-O-hexadecyl-2(R/S, 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl-sn-glycerol (6 showed the most potent cytotoxic activity at CC50 values of 17.5 µM against PC3 cell lines. The replacement of the O-glycosidic linkage by a glycosylamide or a glycosyltriazole linkage showed little or no activity at highest concentration tested (30 µM, whereas the replacement of the glycerol moiety by triazole resulted in CC50 values in the range of 20 to 30 µM. In conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic linkage or triazole-linkage resulted in about a two to three fold loss in activity, whereas the replacement of the methoxy group on the glycerol backbone by a second glucosamine moiety did not improve the activity. The stereochemistry at the C2-position of the glycero backbone has minimal effect on the anticancer activities of these diglycosylated analogs.

Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B.

Science.gov (United States)

Shiozaki, Hiroki; Miyahara, Masayoshi; Otsuka, Kazunori; Miyako, Kei; Honda, Akito; Takasaki, Yuichi; Takamizawa, Satoshi; Tukada, Hideyuki; Ishikawa, Yuichi; Sakai, Ryuichi; Oikawa, Masato

2018-05-23

A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.

Indirect flow injection determination of N-acetyl-L-cysteine using cerium(IV) and ferroin

International Nuclear Information System (INIS)

Vieira, Heberth Juliano; Fatibello-Filho, Orlando

2005-01-01

An indirect flow injection spectrophotometric procedure is proposed for the determination of N-acetyl-L-cysteine in pharmaceutical formulations. In this system, ferroin ([Fe(II)-(fen) 2 ] 2+ ) in excess, with a strong absorption at 500 nm, is oxidized by cerium(IV) yielding cerium(III) and [Fe(III)-(fen) 2 ] 3+ (colorless), thus producing a baseline. When N-acetyl-L-cysteine solution is introduced into the flow injection system, it reacts with cerium(IV) increasing the analytical signal in proportion to the drug concentration. Under optimal experimental conditions, the linearity of the analytical curve for N-acetyl-L-cysteine ranged from 6.5x10 -6 to 1.3x10 -4 mol L -1 . The detection limit was 5.0x10 -6 mol L -1 and recoveries between 98.0 and 106% were obtained. The sampling frequency was 60 determinations per hour and the RSD was smaller than 1.4% for 2.2x10 -5 mol L -1 N-acetyl-L-cysteine. (author)

Potential of Annona muricata L. seed oil: phytochemical and nutritional characterization associated with non-toxicity

Directory of Open Access Journals (Sweden)

L. C. Pinto

2018-03-01

Full Text Available The aim of this study was to evaluate the nutritional quality, phenolic compounds, fatty acid and antioxidant activity in vitro as well as a toxicological screening of A. muricata seed oil in vivo. The chemical composition and quantification of phenolic compounds were determined by the Adolfo Lutz Institute normative. The antioxidant activity was evaluated by DPPH, FRAP and ABTS methods. The oil was extracted by chloroform/ methanol and precipitated crude (AmPtO and supernatant oils (AmSO were obtained. The fatty acid profile was evaluated by gas chromatography and total compounds by HPLC-DAD. BALB/C mice received AmPtO and AmSO (0.5 and 1.0mL·Kg-1 for 14 days. Toxicity parameters were assessed. The major fatty acids in the oil were oleic (39.2% and linoleic (33%. HPLC-DAD suggested the presence of acetogenins (annonacin: 595 [M-H]-, with a greater presence in AmPtO. The AmPtO group showed toxicity, which may be related to the acetogenin content in AmPtO. The AmSO group showed no toxicity and this oil has potential for food or medicinal use.

Piper betle leaves: profiling phenolic compounds by HPLC/DAD-ESI/MS(n) and anti-cholinesterase activity.

Science.gov (United States)

Ferreres, Federico; Oliveira, Andreia P; Gil-Izquierdo, Angel; Valentão, Patrícia; Andrade, Paula B

2014-01-01

Piper betle L. is a widely distributed plant in the tropical and subtropical regions, its leaves being largely consumed as a masticator and mouth freshener. The purposes of this work were to characterise the phenolic profile of this species and to improve knowledge of its anti-cholinesterase properties. The phenolic composition of P. betle leaf aqueous and ethanol extracts was characterised by HPLC coupled with a diode-array detector and combined with electrospray ionisation tandem MS, and in vitro cholinesterase inhibitory capacity of both extracts was assessed by spectrophotometric microassays. The effect on neuronal cells (SH-SY5Y) viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage. Twelve phenolic compounds, comprising a phenylpropanoid, five cinnamoyl and six flavonoids derivatives were identified in P. betle leaves. Hydroxychavicol was the major compound in both extracts; however, the aqueous extract presented a greater diversity of compounds. Both extracts showed strong activity against both acetyl- and butyrylcholinesterase, which can be due, at least partially, to the phenolic composition. Furthermore, the aqueous extract proved to be cytotoxic to human neuroblastoma cells at concentrations higher than 500 µg/mL. The results suggest that the consumption of P. betle leaves as an infusion can have a positive impact in the prevention and treatment of neurodegenerative diseases. Apigenin and luteolin derivatives are reported for the first time in this species. Copyright © 2014 John Wiley & Sons, Ltd.

Non-analog Monte Carlo estimators for radiation momentum deposition

International Nuclear Information System (INIS)

Hykes, Joshua M.; Densmore, Jeffery D.

2009-01-01

The standard method for calculating radiation momentum deposition in Monte Carlo simulations is the analog estimator, which tallies the change in a particle's momentum at each interaction with the matter. Unfortunately, the analog estimator can suffer from large amounts of statistical error. In this paper, we present three new non-analog techniques for estimating momentum deposition. Specifically, we use absorption, collision, and track-length estimators to evaluate a simple integral expression for momentum deposition that does not contain terms that can cause large amounts of statistical error in the analog scheme. We compare our new non-analog estimators to the analog estimator with a set of test problems that encompass a wide range of material properties and both isotropic and anisotropic scattering. In nearly all cases, the new non-analog estimators outperform the analog estimator. The track-length estimator consistently yields the highest performance gains, improving upon the analog-estimator figure of merit by factors of up to two orders of magnitude.

Histones of Chlamydomonas reinhardtii. Synthesis, acetylation, and methylation

International Nuclear Information System (INIS)

Waterborg, J.H.; Robertson, A.J.; Tatar, D.L.; Borza, C.M.; Davie, J.R.

1995-01-01

Histones of the green alga Chlamydomonas reinhardtii were prepared by a new method and fractionated by reversed-phase high-performance liquid chromatography. Acid-urea-Triton gel analysis and tritiated acetate labeling demonstrated high levels of steady-state acetylation for the single histone H3 protein, in contrast to low levels on histones H4 and H2B. Twenty percent of histone H3 is subject to dynamic acetylation with, on average, three acetylated lysine residues per protein molecule. Histone synthesis in light-dark-synchronized cultures was biphasic with pattern differences between two histone H1 variants, between two H2A variants, and between H2B and ubiquitinated H2B. Automated protein sequence analysis of histone H3 demonstrated a site-specific pattern of steady-state acetylation between 7 and 17% at five of the six amino-terminal lysines and of monomethylation between 5 and 81% at five of the eight amino-terminal lysines in a pattern that may limit dynamic acetylation. An algal histone H3 sequence was confirmed by protein sequencing with a since threonine as residue 28 instead of the serine(28)-alanine(29) sequence, present in all other known plant and animal H3 histones

Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

Energy Technology Data Exchange (ETDEWEB)

Yang, Xiupei, E-mail: xiupeiyang@163.com [Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, Nanchong 637000 (China); College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China); Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan [College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China)

2015-06-15

Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH{sub 3}{sup +} moiety of doxorubicin and the −COO{sup −} moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum.

Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

International Nuclear Information System (INIS)

Yang, Xiupei; Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan

2015-01-01

Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH 3 + moiety of doxorubicin and the −COO − moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum

The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis

International Nuclear Information System (INIS)

Mu, J.-J.; Tsay, Y.-G.; Juan, L.-J.; Fu, T.-F.; Huang, W.-H.; Chen, D.-S.; Chen, P.-J.

2004-01-01

Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg is required for viral assembly. In this study, we demonstrated that HDAg are acetylated proteins. Metabolic labeling with [ 3 H]acetate revealed that both forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT) domain of cellular acetyltransferase p300 could acetylate the full-length and the N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication

Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

International Nuclear Information System (INIS)

Toyooka, Tatsushi; Shinmen, Takuya; Aarts, Jac M.M.J.G.; Ibuki, Yuko

2012-01-01

A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.

A proteome-scale study on in vivo protein N(α)-acetylation using an optimized method

DEFF Research Database (Denmark)

Zhang, Xumin; Engholm-Keller, Kasper; Højrup, Peter

2011-01-01

Protein N-terminal acetylation (N(α)-acetylation) is among the most common modifications in eukaryotes. We previously described a simple method to enrich N(α)-modified peptides using CNBr-activated Sepharose resin. A limitation of this method is that an optimal ratio of sample to resin had to be ...

Synthesis of N-Acylated Amino Acid Surfactant from L-Proline and Palmitoyl Chloride

International Nuclear Information System (INIS)

Meutia Fadhilah Hasibuan; Mohd Wahid Samsudin; Rahimi Mohd Yusop; Suria Ramli

2015-01-01

A biodegradable, less toxic and environmentally friendly N-acylated amino acid surfactant was prepared from the amino acid L-proline and palmitoyl chloride through acylation reaction using the Schotten-Baumann reaction condition. The reaction result was a white flake form and the percentage of the crude yield was 72 % with melting point in range of 52 - 58 degree Celsius. Functional group of amide which was detected using Fourier Transform Infrared method showed the presence of N-palmitoyl proline. The purity analysis using High Performance Liquid Chromatography and Thin Layer Chromatography showed the result was a mixture compound. (author)

NON-RACEMIC AMINO ACID PRODUCTION BY ULTRAVIOLET IRRADIATION OF ACHIRAL INTERSTELLAR ICE ANALOGS WITH CIRCULARLY POLARIZED LIGHT

International Nuclear Information System (INIS)

De Marcellus, Pierre; Nuevo, Michel; Danger, Gregoire; Deboffle, Dominique; Le Sergeant d'Hendecourt, Louis; Meinert, Cornelia; Filippi, Jean-Jacques; Meierhenrich, Uwe J.; Nahon, Laurent

2011-01-01

The delivery of organic matter to the primitive Earth via comets and meteorites has long been hypothesized to be an important source for prebiotic compounds such as amino acids or their chemical precursors that contributed to the development of prebiotic chemistry leading, on Earth, to the emergence of life. Photochemistry of inter/circumstellar ices around protostellar objects is a potential process leading to complex organic species, although difficult to establish from limited infrared observations only. Here we report the first abiotic cosmic ice simulation experiments that produce species with enantiomeric excesses (e.e.'s). Circularly polarized ultraviolet light (UV-CPL) from a synchrotron source induces asymmetric photochemistry on initially achiral inter/circumstellar ice analogs. Enantioselective multidimensional gas chromatography measurements show significant e.e.'s of up to 1.34% for ( 13 C)-alanine, for which the signs and absolute values are related to the helicity and number of CPL photons per deposited molecule. This result, directly comparable with some L excesses measured in meteorites, supports a scenario in which exogenous delivery of organics displaying a slight L excess, produced in an extraterrestrial environment by an asymmetric astrophysical process, is at the origin of biomolecular asymmetry on Earth. As a consequence, a fraction of the meteoritic organic material consisting of non-racemic compounds may well have been formed outside the solar system. Finally, following this hypothesis, we support the idea that the protosolar nebula has indeed been formed in a region of massive star formation, regions where UV-CPL of the same helicity is actually observed over large spatial areas.

In Salmonella enterica, the Gcn5-Related Acetyltransferase MddA (Formerly YncA) Acetylates Methionine Sulfoximine and Methionine Sulfone, Blocking Their Toxic Effects

Science.gov (United States)

Hentchel, Kristy L.

2014-01-01

Protein and small-molecule acylation reactions are widespread in nature. Many of the enzymes catalyzing acylation reactions belong to the Gcn5-related N-acetyltransferase (GNAT; PF00583) family, named after the yeast Gcn5 protein. The genome of Salmonella enterica serovar Typhimurium LT2 encodes 26 GNATs, 11 of which have no known physiological role. Here, we provide in vivo and in vitro evidence for the role of the MddA (methionine derivative detoxifier; formerly YncA) GNAT in the detoxification of oxidized forms of methionine, including methionine sulfoximine (MSX) and methionine sulfone (MSO). MSX and MSO inhibited the growth of an S. enterica ΔmddA strain unless glutamine or methionine was present in the medium. We used an in vitro spectrophotometric assay and mass spectrometry to show that MddA acetylated MSX and MSO. An mddA+ strain displayed biphasic growth kinetics in the presence of MSX and glutamine. Deletion of two amino acid transporters (GlnHPQ and MetNIQ) in a ΔmddA strain restored growth in the presence of MSX. Notably, MSO was transported by GlnHPQ but not by MetNIQ. In summary, MddA is the mechanism used by S. enterica to respond to oxidized forms of methionine, which MddA detoxifies by acetyl coenzyme A-dependent acetylation. PMID:25368301

HPLC-DAD-ESI/MS(n) analysis of phenolic compounds for quality control of Grindelia robusta Nutt. and bioactivities.

Science.gov (United States)

Ferreres, Federico; Grosso, Clara; Gil-Izquierdo, Angel; Valentão, Patrícia; Azevedo, Carolina; Andrade, Paula B

2014-06-01

The phenolic composition of herbal tea (HT) and hydromethanolic extract (HME) obtained from Grindelia robusta Nutt. was studied by HPLC-DAD-ESI/MS(n). Thirty six flavonoids and hydroxycinnamic acids were detected, from which thirty are described for the first time in this species. Quantification by HPLC-DAD showed that diosmetin-7-O-glucuronide-3'-O-pentoside+apigenin-7-O-glucuronide-4'-O-pentoside, apigenin-7-O-glucuronide+diosmetin-7-O-glucuronide and 3,5-dicaffeoylquinic acid+3,4-dicaffeoylquinic acid were the major compounds. Since the health-promoting effects of natural phenolic compounds against brain disorders is of increasing interest, HT and HME were also tested against oxygen and nitrogen reactive species and against enzymes related with Alzheimer's disease and depression. Extracts displayed strong in vitro scavenging activity and monoamine oxidase-A (MAO-A) inhibitory activity. The anti-MAO-A capacity was observed at non-toxic concentrations for SH-SY5Y human neuroblastoma cell line, reinforcing the benefits of G. robusta HT. However, no protection against hydrogen peroxide treatment was observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical structure of the adducts formed by the oxidation of benzidine in the presence of phenols

International Nuclear Information System (INIS)

Josephy, P.D.; Mason, R.P.; Eling, T.

1982-01-01

Bioactivation of carcinogens by peroxidases has received increasing attention since the discovery of the oxidation of carcinogens by prostaglandin hydroperoxidase. Benzidine and 3,5,3',5'-tetramethylbenzidine are oxidized by horseradish peroxidase and prostaglandin synthase to two-electron oxidation products (di-imines). Di-imines readily react with the phenolic anti-oxidant butylated hydroxyanisole to form adducts. In this paper, we have studied the oxidation of benzidine by horseradish peroxidase in the presence of phenolic compounds and characterized the resultant benzidine/phenol adducts. A benzidine/2,6-dimethylphenol adduct was isolated and characterized by mass spectrometry and high field n.m.r. The reaction of [ 14 C]benzidine in the presence of horseradish peroxidase and phenol yielded only the benzidine/phenol adduct. Our results indicate that the benzidine/phenol adducts are analogous to the indoaniline dyes, differing only in substitution of a biphenyl group for a benzene ring. The reaction of benzidine di-imine with endogenous phenols may represent a new pathway for detoxication, removing potentially harmful metabolites of benzidine

Optimization of microwave-assisted extraction and pressurized liquid extraction of phenolic compounds from Moringa oleifera leaves by multiresponse surface methodology.

Science.gov (United States)

Rodríguez-Pérez, Celia; Gilbert-López, Bienvenida; Mendiola, Jose Antonio; Quirantes-Piné, Rosa; Segura-Carretero, Antonio; Ibáñez, Elena

2016-07-01

This work aims at studying the optimization of microwave-assisted extraction (MAE) and pressurized liquid extraction (PLE) by multi-response surface methodology (RSM) to test their efficiency towards the extraction of phenolic compounds from Moringa oleifera (M. oleifera) leaves. The extraction yield, total phenolic content (TPC), total flavonoid content (TF), DPPH scavenging method and trolox equivalent antioxidant capacity (TEAC) assay were considered as response variables while effects of extraction time, percentage of ethanol, and temperature were studied. Extraction time of 20 min, 42% ethanol and 158°C were the MAE optimum conditions for achieving extraction yield of 26 ± 2%, EC50 15 ± 2 μg/mL, 16 ± 1 Eq Trolox/100 g dry leaf, 5.2 ± 0.5 mg Eq quercetin/g dry leaf, and 86 ± 4 mg GAE/g dry leaf. Regarding PLE, the optimum conditions that allowed extraction yield of 56 ± 2%, EC50 21 ± 3 μg/mL, 12 ± 2 mmol Eq Trolox/100 g dry leaf, 6.5 ± 0.2 mg Eq quercetin/g dry leaf, and 59 ± 6 mg GAE/g dry leaf were 128°C, 35% of ethanol, and 20 min. PLE enabled the extraction of phenolic compounds with a higher number of hydroxyl-type substituents such as kaempferol diglycoside and its acetyl derivatives and those that are sensitive to high temperatures (glucosinolates or amino acids) while MAE allowed better recoveries of kaempferol, quercetin, and their glucosides derivatives. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum-induced spatial memory deficit in rats.

Science.gov (United States)

Fernandes, Joylee; Mudgal, Jayesh; Rao, Chamallamudi Mallikarjuna; Arora, Devinder; Basu Mallik, Sanchari; Pai, K S R; Nampoothiri, Madhavan

2018-06-01

Neuroinflammation plays an important role in the pathophysiology of Alzheimer's disease. Neurokinin substance P is a key mediator which modulates neuroinflammation through neurokinin receptor. Involvement of substance P in Alzheimer's disease is still plausible and various controversies exist in this hypothesis. Preventing the deleterious effects of substance P using N-acetyl-L-tryptophan, a substance P antagonist could be a promising therapeutic strategy. This study was aimed to evaluate the effect of N-acetyl-L-tryptophan on aluminum induced spatial memory alterations in rats. Memory impairment was induced using aluminum chloride (AlCl 3 ) at a dose of 10 mg/kg for 42 d. After induction of dementia, rats were exposed to 30 and 50 mg/kg of N-acetyl-L-tryptophan for 28 d. Spatial memory alterations were measured using Morris water maze. Acetylcholinesterase activity and antioxidant enzyme glutathione level were assessed in hippocampus, frontal cortex and striatum. The higher dose of N-acetyl-L-tryptophan (50 mg/kg) significantly improved the aluminum induced memory alterations. N-acetyl-L-tryptophan exposure resulted in significant increase in acetylcholinesterase activity and glutathione level in hippocampus. The neuroprotective effect of N-acetyl-L-tryptophan could be due to its ability to block substance P mediated neuroinflammation, reduction in oxidative stress and anti-apoptotic properties. To conclude, N-acetyl-L-tryptophan may be considered as a novel neuroprotective therapy in Alzheimer's disease.

Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages.

Directory of Open Access Journals (Sweden)

Tomokazu Ohnishi

Full Text Available N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

Science.gov (United States)

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Thyroid cancer in toxic and non-toxic multinodular goiter

Directory of Open Access Journals (Sweden)

Cerci C

2007-01-01

Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

Fragrance material review on acetyl carene.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of acetyl carene when used as a fragrance ingredient is presented. Acetyl carene is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for acetyl carene were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013A Toxicologic and dermatologic assessment of alkyl cyclic ketones when used as fragrance ingredients. (submitted for publication).) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013. Published by Elsevier Ltd.

Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

Science.gov (United States)

Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

2011-12-01

In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Improve the biodegradability of post-hydrothermal liquefaction wastewater with ozone: conversion of phenols and N-heterocyclic compounds.

Science.gov (United States)

Yang, Libin; Si, Buchun; Martins, Marcio Arêdes; Watson, Jamison; Chu, Huaqiang; Zhang, Yuanhui; Tan, Xiaobo; Zhou, Xuefei; Zhang, Yalei

2017-04-01

Hydrothermal liquefaction is a promising technology to convert wet biomass into bio-oil. However, post-hydrothermal liquefaction wastewater (PHWW) is also produced during the process. This wastewater contains a high concentration of organic compounds, including phenols and N-heterocyclic compounds which are two main inhibitors for biological treatment. Thus, proper treatment is required. In this work, ozone was used to convert phenols and N-heterocyclic compounds with a dosage range of 0-4.64 mg O 3 /mL PHWW. After ozone treatment, the phenols were fully converted, and acids were produced. However, N-heterocyclic compounds were found to have a low conversion rate (21.7%). The kinetic analysis for the degradation of phenols and N-heterocyclic compounds showed that the substitute played an important role in determining the priority of ozone reactions. The OH moiety in the ring compounds (phenols and pyridinol) may form hydroxyl radical, which lead to an efficient reaction. A substantial improved biodegradability of PHWW was observed after ozone treatment. The ratio of BOD 5 /COD was increased by about 32.36%, and reached a maximum of 0.41. The improved biodegradability of PHWW was justified by the conversion of phenols and N-heterocyclic compounds.

Pharmacokinetics and N-acetylation metabolism of S-methyl-l-cysteine and trans-S-1-propenyl-l-cysteine in rats and dogs.

Science.gov (United States)

Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

2016-11-01

1. Pharmacokinetics and N-acetylation metabolism of S-methyl-L-cysteine (SMC) and trans-S-1-propenyl-L-cysteine (S1PC) were examined in rats and dogs. SMC and S1PC (2-5 mg/kg) were well absorbed in both species with high bioavailability (88-100%). 2. SMC and S1PC were excreted only to a small extent in the urine of rats and dogs. The small renal clearance values (l/h/kg) indicated the extensive renal reabsorption of SMC and S1PC, which potentially contributed to their long elimination half-lives (>5 h) in dogs. 3. S1PC, but not SMC, underwent N-acetylation extensively in vivo, which can be explained by the relative activities of N-acetylation of S1PC/SMC and deacetylation of their N-acetylated forms, N-acetyl-S1PC/N-acetyl-SMC, in the liver and kidney in vitro. The activities for S1PC N-acetylation were similar to or higher than those for N-acetyl-S1PC deacetylation in liver S9 fractions of rat and dog, whereas liver and kidney S9 fractions of rat and dog had little activity for SMC N-acetylation or considerably higher activities for N-acetyl-SMC deacetylation. 4. Our study demonstrated that the pharmacokinetics of SMC and S1PC in rats and dogs was characterized by high bioavailability and extensive renal reabsorption; however, the extent of undergoing the N-acetylation metabolism was extremely different between SMC and S1PC.

Non-natural and photo-reactive amino acids as biochemical probes of immune function.

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Marta Gómez-Nuñez

Full Text Available Wilms tumor protein (WT1 is a transcription factor selectively overexpressed in leukemias and cancers; clinical trials are underway that use altered WT1 peptide sequences as vaccines. Here we report a strategy to study peptide-MHC interactions by incorporating non-natural and photo-reactive amino acids into the sequence of WT1 peptides. Thirteen WT1 peptides sequences were synthesized with chemically modified amino acids (via fluorination and photo-reactive group additions at MHC and T cell receptor binding positions. Certain new non-natural peptide analogs could stabilize MHC class I molecules better than the native sequences and were also able to elicit specific T-cell responses and sometimes cytotoxicity to leukemia cells. Two photo-reactive peptides, also modified with a biotin handle for pull-down studies, formed covalent interactions with MHC molecules on live cells and provided kinetic data showing the rapid clearance of the peptide-MHC complex. Despite "infinite affinity" provided by the covalent peptide bonding to the MHC, immunogenicity was not enhanced by these peptides because the peptide presentation on the surface was dominated by catabolism of the complex and only a small percentage of peptide molecules covalently bound to the MHC molecules. This study shows that non-natural amino acids can be successfully incorporated into T cell epitopes to provide novel immunological, biochemical and kinetic information.

Another Look at Pyrroloiminoquinone Alkaloids—Perspectives on Their Therapeutic Potential from Known Structures and Semisynthetic Analogues

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Sheng Lin

2017-03-01

Full Text Available This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid carcinoma (PANC-1 cell line IC50 data was obtained for 16 compounds and two therapeutic standards. These results along with data gleaned from the literature provided useful structure activity relationship conclusions. Three structural motifs proved to be important in maximizing potency against PANC-1: (i conjugation within the core of the ABC-ring; (ii the presence of a positive charge in the C-ring; and (iii inclusion of a 4-ethyl phenol or 4-ethyl phenol acetate substituent off the B-ring. Two compounds, makaluvamine J (9 and 15-O-acetyl makaluvamine J (15, contained all three of these frameworks and exhibited the best potency with IC50 values of 54 nM and 81 nM, respectively. These two most potent analogs were then tested against the OVCAR-5 cell line and the presence of the acetyl group increased the potency 14-fold from that of 9 whose IC50 = 120 nM vs. that of 15 having IC50 = 8.6 nM.

Non-specific activities of the major herbicide-resistance gene BAR.

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Christ, Bastien; Hochstrasser, Ramon; Guyer, Luzia; Francisco, Rita; Aubry, Sylvain; Hörtensteiner, Stefan; Weng, Jing-Ke

2017-12-01

Bialaphos resistance (BAR) and phosphinothricin acetyltransferase (PAT) genes, which convey resistance to the broad-spectrum herbicide phosphinothricin (also known as glufosinate) via N-acetylation, have been globally used in basic plant research and genetically engineered crops 1-4 . Although early in vitro enzyme assays showed that recombinant BAR and PAT exhibit substrate preference toward phosphinothricin over the 20 proteinogenic amino acids 1 , indirect effects of BAR-containing transgenes in planta, including modified amino acid levels, have been seen but without the identification of their direct causes 5,6 . Combining metabolomics, plant genetics and biochemical approaches, we show that transgenic BAR indeed converts two plant endogenous amino acids, aminoadipate and tryptophan, to their respective N-acetylated products in several plant species. We report the crystal structures of BAR, and further delineate structural basis for its substrate selectivity and catalytic mechanism. Through structure-guided protein engineering, we generated several BAR variants that display significantly reduced non-specific activities compared with its wild-type counterpart in vivo. The transgenic expression of enzymes can result in unintended off-target metabolism arising from enzyme promiscuity. Understanding such phenomena at the mechanistic level can facilitate the design of maximally insulated systems featuring heterologously expressed enzymes.

Impact of high glucose concentration on aspirin-induced acetylation of human serum albumin: An in vitro study

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Francesco Finamore

2014-06-01

Full Text Available Aspirin (ASA plays a key role in protecting high risk cardiovascular patients from ischaemic events. The modifications underlying its effects are the results of the trans-acetylation that occurs between ASA and the amino groups made up of lysine and N-terminal residues. ASA's effects have also been demonstrated on several plasma proteins, including human serum albumin (HSA. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair ASA's acetylation process. Using immunoblotting and mass spectrometry, this study characterized the degree of HSA acetylation mediated by ASA in vitro, as well as the impact of high glucose concentrations. Glycation's influence on HSA acetylation might impair the latter's biological functions, leading to a potential failure of ASA to prevent cardiovascular complications in diabetes.

The reactivity of phenolic and non-phenolic residual kraft lignin model compounds with Mn(II)-peroxidase from Lentinula edodes.

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Crestini, C; D'Annibale, A; Sermanni, G G; Saladino, R

2000-02-01

Three phenolic model compounds representing bonding patterns of residual kraft lignin were incubated with manganese peroxidase from Lentinula edodes. Extensive degradation of all the phenolic models, mainly occurring via side-chain benzylic oxidation, was observed. Among the tested model compounds the diphenylmethane alpha-5 phenolic model was found to be the most reactive, yielding several products showing oxidation and fragmentation at the bridging position. The non-phenolic 5-5' biphenyl and 5-5' diphenylmethane models were found unreactive.

Efficient acetylation of primary amines and amino acids in ...

Indian Academy of Sciences (India)

bDepartment of Clinical and Experimental Pharmacology, School of Tropical Medicine ... As a result ... methods of acetylation of amines are known using ace- ... vents we report here, environmentally benign, eco- ... It was filtered under suction,.

Dual Effect of Phenolic Nectar on Three Floral Visitors of Elsholtzia rugulosa (Lamiaceae) in SW China.

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Zhang, Feng-Ping; Yang, Qiu-Yun; Zhang, Shi-Bao

2016-01-01

Some plants secrete toxic nectar to appeal to most effective pollinators and deter non-pollinators or nectar thieves; however available information about ecological function of toxic nectar remains scarce. Elsholtzia rugulosa stands out as a plant with toxic nectar recorded in SW China. We focused on the functional significance of the phenolic compound that imparts toxic to the nectar of E. rugulosa. The effects of phenolic nectar were studied in three visitors of the flowers of the winter-blooming E. rugulosa Hemsl. (Lamiaceae) in SW China. The pollinating species Apis cerana Fabricius (Apidae; Asian honey bee) and two occasional visitors, Vespa velutina Lepeletier (Vespidae; yellow-legged Asian hornet) and Bombus eximius Smith (Apidae; a bumble bee) were tested for their preferences for low and high concentrations of 4-hydroxybenzoic acid in hexose and sucrose solutions. The pollinator is important for the plant, which is dependent on pollinator visits to attain a higher seed production and it is most likely that the combination of phenolic toxic nectar and the adaptation to phenolic nectar by A. cerana delivers an evolutionary advantage to both actors. The low and high concentrations of the phenolic acid were nearly totally refused by both occasional visitors V. velutina and B. eximius and were preferred by the pollinator A. cerana. E. rugulosa gains by having a much higher seed production and the pollinating honey bee by having an exclusive and reliable food source during the winter season at high altitudes in SW China. We found that the function of the toxic phenolic compound has dual roles by appealing to legitimate pollinators and deterring non-pollinators of E. rugulosa.

Dual Effect of Phenolic Nectar on Three Floral Visitors of Elsholtzia rugulosa (Lamiaceae in SW China.

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Feng-Ping Zhang

Full Text Available Some plants secrete toxic nectar to appeal to most effective pollinators and deter non-pollinators or nectar thieves; however available information about ecological function of toxic nectar remains scarce. Elsholtzia rugulosa stands out as a plant with toxic nectar recorded in SW China. We focused on the functional significance of the phenolic compound that imparts toxic to the nectar of E. rugulosa. The effects of phenolic nectar were studied in three visitors of the flowers of the winter-blooming E. rugulosa Hemsl. (Lamiaceae in SW China. The pollinating species Apis cerana Fabricius (Apidae; Asian honey bee and two occasional visitors, Vespa velutina Lepeletier (Vespidae; yellow-legged Asian hornet and Bombus eximius Smith (Apidae; a bumble bee were tested for their preferences for low and high concentrations of 4-hydroxybenzoic acid in hexose and sucrose solutions. The pollinator is important for the plant, which is dependent on pollinator visits to attain a higher seed production and it is most likely that the combination of phenolic toxic nectar and the adaptation to phenolic nectar by A. cerana delivers an evolutionary advantage to both actors. The low and high concentrations of the phenolic acid were nearly totally refused by both occasional visitors V. velutina and B. eximius and were preferred by the pollinator A. cerana. E. rugulosa gains by having a much higher seed production and the pollinating honey bee by having an exclusive and reliable food source during the winter season at high altitudes in SW China. We found that the function of the toxic phenolic compound has dual roles by appealing to legitimate pollinators and deterring non-pollinators of E. rugulosa.

Alkoxyl- and carbon-centered radicals as primary agents for degrading non-phenolic lignin-substructure model compounds.

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Ohashi, Yasunori; Uno, Yukiko; Amirta, Rudianto; Watanabe, Takahito; Honda, Yoichi; Watanabe, Takashi

2011-04-07

Lignin degradation by white-rot fungi proceeds via free radical reaction catalyzed by oxidative enzymes and metabolites. Basidiomycetes called selective white-rot fungi degrade both phenolic and non-phenolic lignin substructures without penetration of extracellular enzymes into the cell wall. Extracellular lipid peroxidation has been proposed as a possible ligninolytic mechanism, and radical species degrading the recalcitrant non-phenolic lignin substructures have been discussed. Reactions between the non-phenolic lignin model compounds and radicals produced from azo compounds in air have previously been analysed, and peroxyl radical (PR) is postulated to be responsible for lignin degradation (Kapich et al., FEBS Lett., 1999, 461, 115-119). However, because the thermolysis of azo compounds in air generates both a carbon-centred radical (CR) and a peroxyl radical (PR), we re-examined the reactivity of the three radicals alkoxyl radical (AR), CR and PR towards non-phenolic monomeric and dimeric lignin model compounds. The dimeric lignin model compound is degraded by CR produced by reaction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which under N(2) atmosphere cleaves the α-β bond in 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol to yield 4-ethoxy-3-methoxybenzaldehyde. However, it is not degraded by the PR produced by reaction of Ce(4+)/tert-BuOOH. In addition, it is degraded by AR produced by reaction of Ti(3+)/tert-BuOOH. PR and AR are generated in the presence and absence of veratryl alcohol, respectively. Rapid-flow ESR analysis of the radical species demonstrates that AR but not PR reacts with the lignin model compound. Thus, AR and CR are primary agents for the degradation of non-phenolic lignin substructures.

Structural Characterization of Amadori Rearrangement Product of Glucosylated Nα-Acetyl-Lysine by Nuclear Magnetic Resonance Spectroscopy

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Chuanjiang Li

2014-01-01

Full Text Available Maillard reaction is a nonenzymatic reaction between reducing sugars and free amino acid moieties, which is known as one of the most important modifications in food science. It is essential to characterize the structure of Amadori rearrangement products (ARPs formed in the early stage of Maillard reaction. In the present study, the Nα-acetyl-lysine-glucose model had been successfully set up to produce ARP, Nα-acetyl-lysine-glucose. After HPLC purification, ARP had been identified by ESI-MS with intense [M+H]+ ion at 351 m/z and the purity of ARP was confirmed to be over 90% by the relative intensity of [M+H]+ ion. Further structural characterization of the ARP was accomplished by using nuclear magnetic resonance (NMR spectroscopy, including 1D 1H NMR and 13C NMR, the distortionless enhancement by polarization transfer (DEPT-135 and 2D 1H-1H and 13C-1H correlation spectroscopy (COSY and 2D nuclear overhauser enhancement spectroscopy (NOESY. The complexity of 1D 1H NMR and 13C NMR was observed due to the presence of isomers in glucose moiety of ARP. However, DEPT-135 and 2D NMR techniques provided more structural information to assign the 1H and 13C resonances of ARP. 2D NOESY had successfully confirmed the glycosylated site between 10-N in Nα-acetyl-lysine and 7′-C in glucose.

Synthesis and Biological Activity of Novel Amino Acid-(N'-Benzoyl Hydrazide and Amino Acid-(N'-Nicotinoyl Hydrazide Derivatives

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Sherine N. Khattab

2005-09-01

Full Text Available The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N`-benzoyl- and N- Boc-amino acid-(N`-nicotinoyl hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N`-benzoyl hydrazide hydrochloride salts (7a-7e and amino acid-(N`- nicotinoyl hydrazide hydrochloride salts (8a-8e. These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.

Evaluation of toxicity and biodegradability of cholinium amino acids ionic liquids.

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Xue-Dan Hou

Full Text Available Cholinium amino acid ionic liquids ([Ch][AA] ILs, which are wholly composed of renewable biomaterials, have recently been demonstrated to have very promising properties for applications in organic synthesis and biomass pretreatment. In this work, the toxicity of these ILs toward enzymes and bacteria was assessed, and the effect of the anion on these properties is discussed. The inhibitory potentials of this type of ILs to acetylcholinesterase were weaker approximately an order of magnitude than the traditional IL 1-butyl-3-methylimidazolium tetrafluoroborate. Additionally, the [Ch][AA] ILs displayed low toxicity toward the bacteria tested. Furthermore, the biodegradability of the [Ch][AA] ILs was evaluated via the closed bottle and CO(2 headspace tests using wastewater microorganisms. All the ILs were classified as 'readily biodegradable' based on their high levels of mineralization (62-87%. The presence of extra carboxyl or amide groups on the amino acid side chain rendered the ILs significantly more susceptible to microbial breakdown. In addition, for most of the [Ch][AA] ILs, low toxicity correlated with good biodegradability. The low toxicity and high biodegradability of these novel [Ch][AA] make them promising candidates for use as environmentally friendly solvents in large-scale applications.

Reactivity of Biliatresone, a Natural Biliary Toxin, with Glutathione, Histamine, and Amino Acids.

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Koo, Kyung A; Waisbourd-Zinman, Orith; Wells, Rebecca G; Pack, Michael; Porter, John R

2016-02-15

In our previous work, we identified a natural toxin, biliatresone, from Dysphania glomulifera and D. littoralis, endemic plants associated with outbreaks of biliary atresia in Australian neonatal livestock. Biliatresone is a very rare isoflavonoid with an α-methylene ketone between two phenyls, 1,2-diaryl-2-propenone, along with methylenedioxy, dimethoxyl, and hydroxyl functional groups, that causes extrahepatic biliary toxicity in zebrafish. The toxic core of biliatresone is a methylene in the α-position relative to the ketone of 1,2-diaryl-2-propenone that serves as an electrophilic Michael acceptor. The α-methylene of biliatresone spontaneously conjugated with water and methanol (MeOH), respectively, via Michael addition in a reverse phase high-performance liquid chromatography (RP-HPLC) analysis. We here report the reactivity of biliatresone toward glutathione (GSH), several amino acids, and other thiol- or imidazole-containing biomolecules. LC-MS and HPLC analysis of the conjugation reaction showed the reactivity of biliatresone to be in the order histidine > N-acetyl-d-cysteine (D-NAC) = N-acetyl-l-cysteine (L-NAC) > histamine > glutathione ≥ cysteine ≫ glycine > glutamate > phenylalanine, while serine and adenine had no reactivity due to intramolecular hydrogen bonding in the protic solvents. The reactivity of ethyl vinyl ketone (EVK, 1-penten-3-one), an example of a highly reactive α,ß-unsaturated ketone, toward GSH gave a 6.7-fold lower reaction rate constant than that of biliatresone. The reaction rate constant of synthetic 1,2-diaryl-2-propen-1-one (DP), a core structure of the toxic molecule, was 10-fold and 1.5-fold weaker in potency compared to the reaction rate constants of biliatresone and EVK, respectively. These results demostrated that the methylenedioxy, dimethoxyl, and hydroxyl functional groups of biliatresone contribute to the stronger reactivity of the Michael acceptor α-methylene ketone toward nucleophiles compared to that of DP

Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate.

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Zhao, Gengxiang; Jin, Zhongmin; Allewell, Norma M; Tuchman, Mendel; Shi, Dashuang

2015-01-01

Structures of the catalytic N-acetyltransferase (NAT) domain of the bifunctional N-acetyl-L-glutamate synthase/kinase (NAGS/K) from Xylella fastidiosa bound to N-acetyl-L-glutamate (NAG) with and without an N-terminal His tag have been solved and refined at 1.7 and 1.4 Å resolution, respectively. The NAT domain with an N-terminal His tag crystallized in space group P4(1)2(1)2, with unit-cell parameters a=b=51.72, c=242.31 Å. Two subunits form a molecular dimer in the asymmetric unit, which contains ∼41% solvent. The NAT domain without an N-terminal His tag crystallized in space group P21, with unit-cell parameters a=63.48, b=122.34, c=75.88 Å, β=107.6°. Eight subunits, which form four molecular dimers, were identified in the asymmetric unit, which contains ∼38% solvent. The structures with and without the N-terminal His tag provide an opportunity to evaluate how the His tag affects structure and function. Furthermore, multiple subunits in different packing environments allow an assessment of the plasticity of the NAG binding site, which might be relevant to substrate binding and product release. The dimeric structure of the X. fastidiosa N-acetytransferase (xfNAT) domain is very similar to that of human N-acetyltransferase (hNAT), reinforcing the notion that mammalian NAGS is evolutionally derived from bifunctional bacterial NAGS/K.

A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents.

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Patil, Pravin C; Satam, Vijay; Lee, Moses

2015-01-01

The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, the intensity in the design, synthesis, and development of novel analogs of the duocarmycins has continued. Accordingly, in this review, which covers a period from the 1990s through the present time, the design and synthesis of duocarmycin SA are described along with the synthesis of novel and highly cytotoxic analogs that lack the chiral center. Examples of achiral analogs of duocarmycin SA described in this review include seco-DUMSA (39 and 40), seco-amino-CBI-TMI (13, Centanamycin), and seco-hydroxy-CBI-TMI (14). In addition, another novel class of biologically active duocarmycin SA analogs that contained the seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) DNA alkylating submit was also designed and synthesized. The synthesis of seco-iso-CFI-TMI (10, Tafuramycin A) and seco-CFQ-TMI (11, Tafuramycin B) is included in this review.

An allostatic mechanism for M2 pyruvate kinase as an amino-acid sensor.

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Yuan, Meng; McNae, Iain W; Chen, Yiyuan; Blackburn, Elizabeth A; Wear, Martin A; Michels, Paul A M; Fothergill-Gilmore, Linda A; Hupp, Ted; Walkinshaw, Malcolm D

2018-05-10

We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer-monomer dissociation K d is estimated to be ~0.9 µM with a slow dissociation rate (t 1/2 ~ 15 min). X-ray structures of M2PYK complexes with alanine, phenylalanine, and tryptophan show the M2PYK locked in an inactive T-state conformation, while activators lock the M2PYK tetramer in the active R-state conformation. Amino-acid binding in the allosteric pocket triggers rigid body rotations (11°) stabilising either T or R-states. The opposing inhibitory and activating effects of the non-essential amino acids serine and alanine suggest that M2PYK could act as a rapid-response nutrient sensor to rebalance cellular metabolism. This competition at a single allosteric site between activators and inhibitors provides a novel regulatory mechanism by which M2PYK activity is finely tuned by the relative (but not absolute) concentrations of activator and inhibitor amino acids. Such 'allostatic' regulation may be important in metabolic reprogramming and influencing cell fate. ©2018 The Author(s).

Synthesis of Poly(N-vinyl-2-pyrrolidone-co-methyl methacrylate by Maghnite-H+ a Non-toxic Catalyst

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Mohamed Benadda

2014-10-01

Full Text Available In the present work poly (N-vinyl-2-pyrrolidone-co-methyl methacrylate copolymers were prepared successfully and cleanly by a one step process via cationic copolymerization of N-vinyl-2-pyrrolidone (NVP with methyl methacrylate (MMA, in heterogeneous phase using “Maghnite-H+” (Mag-H+ as catalyst in bulk, Maghnite is a montmorillonite sheet silicate clay exchanged with protons to produce Maghnite-H+. Temperature is varied between 20 and 80 °C. The effects of reaction temperature, amount of Mag-H+ on the yield and the intrinsic viscosity (η were investigated. A typical reaction product of poly (NVP-co- MMA was analyzed by infra red spectroscopy (FTIR and 1H-NMR, 13C-NMR spectroscopy as well as by viscosimetry. © 2014 BCREC UNDIP. All rights reservedReceived: 24th November 2013; Revised: 30th June 2014; Accepted: 8th July 2014How to Cite: Benadda, M., Ferrahi, M.I., Belbachir, M. (2014. Synthesis of Poly(N-vinyl-2-pyrrolidone-co-methyl methacrylate by Maghnite-H+ a Non-toxic Catalyst. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (3: 201-206. (doi: 10.9767/bcrec.9.3.5743.201-206Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.3.5743.201-206

Effect of [L-Carnitine] on acetyl-L-carnitine production by heart mitochondria

International Nuclear Information System (INIS)

Bieber, L.L.; Lilly, K.; Lysiak, W.

1986-01-01

The authors recently reported a large efflux of acetyl-L-carnitine from rat heart mitochondria during state 3 respiration with pyruvate as substrate both in the presence and absence of malate. In this series of experiments, the effect of the concentration of L-carnitine on the efflux of acetyl-L-carnitine and on the production of 14 CO 2 from 2- 14 C-pyruvate was determined. Maximum acetylcarnitine production (approximately 25 n moles/min/mg protein) was obtained at 3-5 mM L-carnitine in the absence of added malate. 14 CO 2 production decreased as the concentration of L-carnitine increased; it plateaued at 3-5 mM L-carnitine. These data indicate carnitine can stimulate flux of pyruvate through pyruvate dehydrogenase and can reduce flux of acetyl CoA through the Krebs cycle by acting as an acceptor of the acetyl moieties of acetyl CoA generated by pyruvate dehydrogenase

2-Acetylthiamin pyrophosphate (acetyl-TPP) pH-rate profile for hydrolysis of acetyl-TPP and isolation of acetyl-TPP as a transient species in pyruvate dehydrogenase catalyzed reactions

International Nuclear Information System (INIS)

Gruys, K.J.; Datta, A.; Frey, P.A.

1989-01-01

Rate constants for the hydrolysis of acetyl-TPP were measured pH values of 2.5 and 7.5 and plotted as log k obs versus pH. The pH-rate profile defined two legs, each with a slope of +1 but separated by a region of decreased slope between pH 4 and pH 6. The rates were insensitive to buffer concentrations. Each leg of the profile reflected specific-base-catalyzed hydrolysis of acetyl-TPP, analogous to the hydrolysis of 2-acetyl-3,4-dimethylthiazolium ion. The separation of the two legs of this profile has been shown to be caused by the ionization of a group exhibiting a pK a of 4.73 within acetyl-TPP that is remote from the acetyl group, the aminopyrimidine ring, which is promoted below pH 4.73. The protonation level of this ring has been shown to control the equilibrium partitioning of acetyl-TPP among its carbinolamine, keto, and hydrate forms. The differential partitioning of these species is a major factor causing the separation between the two legs of the pH-rate profile. The characteristic pH-rate profile and the availability of synthetic acetyl-TPP have facilitated the isolation and identification of [1- 14 C]acetyl-TPP from acid-quenched enymatic reaction mixtures at steady states. [1- 14 C]Acetyl-TPP was identified as a transient species in reactions catalyzed by the PDH complex or the pyruvate dehydrogenase component of the complex (E 1 ). The pH-rate profile for hydrolysis of [1- 14 C]-acetyl-TPP, isolated from enzymatic reactions was found to be indistinguishable from that for authentic acetyl-TPP, which constituted positive identification of the 14 C-labeled enzymic species

Synthesis, crystal and supramolecular structure of rac-N-acetyl-2- thiohydantoin-asparagine

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Gerzon E. Delgado

2014-05-01

Full Text Available The title compound, C7H9N3O3S, also known as rac-N-acetyl-5-propionamide-2-thioxo-imidazolidin-4-one, crystallize in the monoclinic system with space group P21/n (Nº14, Z=4, and unit cell parameters a= 9.338 (7 Å, b= 7.545 (5 Å, c= 13.212 (10 Å, E= 97.10 (2°, V= 932.8 (12 Å3. The acetyl group and the mean plane of the ureido group form an angle of 81.0 (2°. In the supramolecular structure, the molecules are joined by N--H···O hydrogen bonds into cyclic structures with graph-set R2 2(14 and R2 2(16, forming a three-dimensional network.

Synthesis and dyeing performance of bisazo disperse dyes based on 3-[4-(4-amino-2-chlorophenoxyanilino]phenol

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Rajesh H. Parab

2016-09-01

Full Text Available The present communication aims to develop bisazo disperse dyes based on 3-[4-(4-amino-2-chlorophenoxyanilino]phenol (DAP both as a coupling component as well as a diazonium salt. Coupling reaction of DAP was carried out with a diazonium salt of 4-aminoacetanilide to yield a monoazo disperse dye, and then it was further used as a diazonium salt and coupled with a different aromatic phenol to synthesize bisazo disperse dyes. All the disperse dyes were characterized by elemental analysis, IR, NMR and UV–Visible spectral studies with a view to determine their chemical structure. The dyeing ability of these bisazo disperse dyes has been evaluated in terms of their dyeing behavior and fastness properties on different fabrics.

The experience of the Use of Essential Amino Acids and Their Keto-analogs in Children with Chronic Kidney Disease

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S.V. Kushnirenko

2013-02-01

Full Text Available This article explored the possibility of prolonged use of low-protein diet, 0.8 g/kg/day in combination with essential keto-analogs of amino acids in children with chronic kidney disease stage 4 to maximize the predialysis period. Long-term low-protein diet in combination with amino acids keto-analogs hadn’t negative impact on laboratory indices of the nutritional status, as well as had favorable effect on the correction of metabolic acidosis and disorders of calcium-phosphorus metabolism. During intake of amino acids keto-analogs there had been marked a distinct tendency to preserve the level of creatinine and significant reduction in the level of urea in the blood serum, which helped to keep the current level of azotemia in 18 patients (90 %. In 2 patients (10 % dialysis program had been started. In the control group by the end of the study period, the need for renal replacement therapy occurred in 4 patients (23.5 %. Dynamics of glomerular filtration rate in the two treatment groups showed a decrease in this indicator in an average of 2 ml/min per year in patients treated with low-protein diet in combination with Ketosteril, and 6 ml/min per year in the control group.

Introdução ao método de pesquisa das paixões "tóxicas": do raciocínio por analogia à semiologia psicanalítica Introduction to the research method of 'toxic' passions: from reasoning by analogy to psychoanalitical semiology

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Victor Eduardo Silva Bento

2009-01-01

Full Text Available Tratou-se de pesquisa de revisão crítica da literatura no campo da epistemologia. Partiu-se da hipótese das paixões "tóxicas", isto é, de que existe uma analogia funcional entre as paixões e as toxicomanias devido à função do excesso narcísico, semelhante, mas não idêntica, em ambas. O objetivo foi introduzir os fundamentos teóricos dos métodos de pesquisa qualitativa desta hipótese, partindo-se do raciocínio por analogia na direção da semiologia psicanalítica. Mais precisamente, pretendeu-se discutir, em nível introdutório, alguns fundamentos teóricos destes métodos vistos como análogos, com dupla finalidade: equacionar uma formulação da hipótese das paixões "tóxicas" de acordo com estes métodos; e estruturar um plano de estudo teórico de caráter psicanalítico, em debate interdisciplinar, adequado a esta formulação, a ser executado em outras investigações a partir da aplicação destes métodos na pesquisa desta hipótese.We have made a search of critical revision about the literature in epistemology. We started from the "toxic" passions hypothesis, that is, from the assumption according to which there is a functional analogy between passions and toxicomanias: the function of the excess of narcissism, similar, but not identical, in both of them. The objective was to introduce the theoretical basis of the qualitative search method of this hypothesis, starting from the analogical reasoning to psychoanalytical semiology. More exactly, we intended to introduce the discussion about the theoretical foundations of these methods, which we consider analogous, with a double purpose: 1st- to formulate the "toxic" passions hypothesis according to these methods; and 2nd- to make a theoretical plan of study in psychoanalysis, result of discussions among other interdisciplinary approaches. Such a plan, elaborated according to this formulation, could be executed later through the application of these methods to the search

[Role of the vitamin factor in preventing phenol poisoning].

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Skvortsova, R I; Pozniakovskiĭ, V M; Agarkova, I A

1981-01-01

Experiments on rats were made to examine the effect of vitamin B1, pantothenic and ascorbic acids on the acetylation system and some characteristics of protein metabolism under chronic exposure to phenol. Inhibition of phenol vapours led to inhibition of the acetylation on the 105th day of the experiment, to accumulation of pyruvic acid by the blood and diurnal urine, to elevation of cholesterol content in the blood serum. The total content of protein and protein fractions in the blood serum remained unchanged. Additional vitaminization of the animals with thiamine (150 micrograms), calcium pantothenate (650 micrograms) or with their mixture containing ascorbic acid (2 mg) resulted in normalization of the test characteristics of carbohydrate and fat metabolism. The data obtained and the clinical trials carried out by the authors suggest introduction of the physiological doses of thiamine, calcium pantothenate and ascorbic acid into the diet of the workers in order to prevent phenol poisonings more effectively.

Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

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Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

2017-06-01

With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Biophysical characterization of the strong stabilization of the RNA triplex poly(U•poly(A*poly(U by 9-O-(ω-amino alkyl ether berberine analogs.

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Debipreeta Bhowmik

Full Text Available Binding of two 9-O-(ω-amino alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U(•poly(A(*poly(U was studied by various biophysical techniques.Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5 °C compared to a 17.5 °C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain.Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena.

Various methods for determination of the degree of N-acetylation of chitin and chitosan: a review.

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Kasaai, Mohammad R

2009-03-11

Chitin, chitosan, and their derivatives have been identified as versatile biopolymers for a broad range of agriculture and food applications. Up to now, several methods have been developed to determine degree of N-acetylation, DA, for chitin and chitosan. In this article, an effort has been made to review the available literature information on the DA determination. These methods are classified into three categories: (1) spectroscopy (IR, (1)H NMR, (13)C NMR, (15)N NMR, and UV); (2) conventional (various types of titration, conductometry, potentiometry, ninhydrin assay, adsorption of free amino groups of chitosan by pictric acid); (3) destructive (elemental analysis, acid or enzymatic hydrolysis of chitin/chitosan and followed by the DA measurement by colorimetry or high performance liquid chromatography, pyrolysis-gas chromatography, and thermal analysis using differential scanning calorimetry) methods. These methods have been compared for their performances and limitations as well as their advantages and disadvantages. The use of IR and NMR spectroscopy methods provides a number of advantages. They do not need long-term procedures to prepare samples, and they provide information on the chemical structure. (1)H NMR and UV techniques are more sensitive than IR, (13)C NMR, and (15)N NMR spectroscopy. The IR technique is mostly used for a qualitative evaluation and comparison studies. Conventional methods are not applicable for highly acetylated chitin. The results of the latter methods are affected by ionic strength of the solvent, pH, and temperature of solution. In destructive methods, longer times are needed for the measurements compared to spectroscopy and conventional methods, but they are applicable for the entire range of the DA.

Aerosol-Forming Reactions of Glyoxal, Methylglyoxal and Amino Acids in Clouds

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de Haan, D. O.; Smith, K. W.; Stroik, D. R.; Corrigan, A. L.; Lee, F. E.; Phan, J. T.; Conley, A. C.

2008-12-01

Glyoxal and methylglyoxal are two common aldehydes present in fog and cloud water. Amino acids are present in clouds at similar concentrations. Here we present bulk and aerosol mass spectroscopic data demonstrating that irreversible reactions between glyoxal and amino acids, triggered by droplet evaporation, produce N-derivatized imidazole compounds along with deeply colored Maillard reaction products. These reactions can occur in the dark and in the absence of oxidants. Reactions between methylglyoxal and amino acids produce analogous methylated products plus oligomers with masses up to m/z = 1000. These reactions, which go to completion on the 10-min-timescale of cloud processing, could be significant sources of secondary organic aerosol and humic-like substances (HULIS or brown carbon).

Cadmium toxicity induced contrasting patterns of concentrations of free sarcosine, specific amino acids and selected microelements in two Noccaea species.

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Zemanová, Veronika; Pavlík, Milan; Pavlíková, Daniela

2017-01-01

Cadmium (Cd) toxicity affects numerous metabolic processes in plants. In the presence of Cd, plants accumulate specific amino acids which may be beneficial to developing Cd tolerance. Our study aimed to characterize the changes in the metabolism of selected free amino acids that are associated with Cd tolerance, and investigate the levels of selected microelements in order to relate these changes to the adaptation strategies of two metallophytes-Noccaea caerulescens (Redlschlag, Austria) and Noccaea praecox (Mežica, Slovenia). The plants were exposed to Cd contamination (90 mg Cd/kg soil) for 120 days in a pot experiment. Our results showed higher Cd accumulation in N. praecox compared to N. caerulescens. Cadmium contamination reduced the zinc and nickel levels in both species and a mixed effect was determined for copper and manganese content. Differences in free amino acid metabolism were observed between the two metallophytes growing under Cd-free and Cd-loaded conditions. Under Cd-free conditions, aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) were accumulated more in the leaves of N. praecox than in N. caerulescens. Cd stress increased the content of these amino acids in both species but this increase was significant only in N. caerulescens leaves. Marked differences in the responses of the two species to Cd stress were shown for alanine, phenylalanine, threonine and sarcosine. Cadmium contamination also induced an increase of threonine as alanine and sarcosine decrease, which was larger in N. caerulescens than in N. praecox. All these factors contribute to the higher adaptation of N. praecox to Cd stress.

Radioiodine therapy in non-toxic multinodular goitre

International Nuclear Information System (INIS)

Miah, S.R.; Rahman, H.

2007-01-01

Full text: The effect of radioiodine in the treatment of non-toxic multinodular goitre has not been adequately evaluated. The aim of the study was to see the effect of radioiodine on thyroid size and function in patients with non-toxic multinodular goitre. We prospectively studied 55 non-toxic multinodular goitre patients treated with radioiodine of which 15 were males and 40 were females with age ranged from 25 years to 60 years (mean ± SD 40.45 ± 10.70 years) for a minimum of 12 months. Patients who were selected were those with local compression symptoms or for cosmetic reasons and the treatment was chosen because of a high operative risk or refusal to be operated on. Thyroid volume and T3, T4, TSH of all patients were determined before treatment and 6 months interval after treatment. Radioiodine was given in the dose ranged from 333 MBq (9 mCi) to 555 MBq (15 mCi) (mean ± SD 11.45 ± 2.04 mCi). The mean thyroid volume was reduced from 44.75 ± 37.44 ml to 28.76 ± 27.25 ml at 12 months (p < 0.001) i.e., reduced by 35.73%. Thyroid volume reduction at 6 months was 21.07%. Hypothyroidism occurred in 9.1% of the patients at 12 months. Side effects were few. Three cases developed radiation thyroiditis and two cases developed hyperthyroidism that was managed conservatively. It has been concluded that radioiodine is effective and well tolerated in the treatment of non-toxic multinodular goitre and may be the treatment of choice in elderly patients, in patients in whom surgery is contraindicated and in patients who are unwilling to undergo surgery. (author)

RESPONSE OF PHENOLIC METABOLISM INDUCED BY ALUMINIUM TOXICITY IN FAGOPYRUM ESCULENTUM MOENCH. PLANTS.

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Smirnov, O E; Kosyan, A M; Kosyk, O I; Taran, N Yu

2015-01-01

Buckwheat genus (Fagopyrum Mill.) is one of the aluminium tolerant taxonomic units of plants. The aim of the study was an evaluation of the aluminium (50 μM effect on phenolic accumulation in various parts of buckwheat plants (Fagopyrum esculentum Moench). Detection of increasing of total phenolic content, changes in flavonoid and anthocyanin content and phenylalanine ammonia-lyase activity (PAL) were revealed over a period of 10 days of exposure to aluminium. The most significant effects of aluminium treatment on phenolic compounds accumulation were total phenolic content increasing (by 27.2%) and PAL activity rising by 2.5 times observed in leaves tissues. Received data could be helpful to understand the aluminium tolerance principles and relationships of phenolic compounds to aluminium phytotoxicity.

Bioassay of Phenol and its Intermediate Products Using Daphnia magna

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Afshin Maleki

2008-06-01

Full Text Available Phenol is one of the most common compounds found in many industrial effluents such as petroleum refining and petrochemicals, pharmaceuticals, pesticides, paint and dye industries, organic chemicals manufacturing, etc. The contamination of bodies of water with phenol is a serious problem in terms of environmental considerations due to its high toxicity. In this study, toxicity of phenol and its degradation mixtures by sonochemical, photochemical, and photosonochemical processes were investigated. Toxicity assay tests were carried out using Daphnia magna as a bio-indicator. The sonochemical and photochemical experiments were carried out using a bath sonicator (500 W working at 35 and 130 kHz frequencies and with a 400 W medium pressure mercury lamp, respectively. Experiments were performed at initial concentrations of 100 mg L-1. Bioassay tests showed that phenol was toxic to D.magna and so resulted in quite low LC50 values. Comparison of toxicity units (TU between phenol and effluent toxicity showed that TU value for photosonochemical effluent was lower than that obtained for phenol, photochemical effluent, and sonochemical effluent. It was found that the toxicity unit of photochemical effluent was lower than that obtained for sonochemical effluent. According to the D.magna acute toxicity test, it is concluded that photosonolysis and photolysis are capable of decreasing the toxicity of by-products formed during the degradation of phenol aqueous solutions. Photosonic and photolytic processes can, therefore, be recommended as a potential approach to the treatment of phenolic wastewater.

Amino acids as possible alternative nitrogen source for growth of Euglena gracilis Z in life support systems.

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Richter, P R; Liu, Y; An, Y; Li, X; Nasir, A; Strauch, S M; Becker, I; Krüger, J; Schuster, M; Ntefidou, M; Daiker, V; Haag, F W M; Aiach, A; Lebert, M

2015-01-01

In recent times Euglena gracilis Z was employed as primary producer in closed environmental life-support system (CELSS), e.g. in space research. The photosynthetic unicellular flagellate is not capable of utilizing nitrate, nitrite, and urea as nitrogen source. Therefore, ammonium is supplied as an N-source in the lab (provided as diammonium-dihydrogenphosphate, (NH4)2HPO4) to E. gracilis cultures. While nitrate exerts low toxicity to organisms, ammonium is harmful for many aquatic organisms especially, at high pH-values, which causes the ionic NH4+ (low toxicity) to be partially transformed into the highly toxic ammonia, NH3. In earlier reports, Euglena gracilis was described to grow with various amino acids as sole N-source. Our aim was to investigate alternatives for (NH4)2HPO4 as N-source with lower toxicity for organisms co-cultivated with Euglena in a CELSS. The growth kinetics of Euglena gracilis cultures was determined in the presence of different amino acids (glycine, glutamine, glutamic acid, leucine, and threonine). In addition, uptake of those amino acids by the cells was measured. Cell growth in the presence of glycine and glutamine was quite comparable to the growth in (NH4)2HPO4 containing cultures while a delay in growth was observed in the presence of leucine and threonine. Unlike, aforementioned amino acids glutamate consumption was very poor. Cell density and glutamate concentration were almost unaltered throughout the experiment and the culture reached the stationary phase within 8 days. The data are compared with earlier studies in which utilization of amino acids in Euglena gracilis was investigated. All tested amino acids (glutamate with limitations) were found to have the potential of being an alternative N-source for Euglena gracilis. Hence, these amino acids can be used as a non-toxic surrogate for (NH4)2HPO4. Copyright © 2014 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.

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Huang, Chao; Zhang, Zhe; Chen, Lihan; Lee, Hank W; Ayrapetov, Marina K; Zhao, Ting C; Hao, Yimei; Gao, Jinsong; Yang, Chunzhang; Mehta, Gautam U; Zhuang, Zhengping; Zhang, Xiaoren; Hu, Guohong; Chin, Y Eugene

2018-06-01

Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G 2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation. Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR . ©2018 American Association for Cancer Research.

A novel sol-gel-based amino-functionalized fiber for headspace solid-phase microextraction of phenol and chlorophenols from environmental samples

Energy Technology Data Exchange (ETDEWEB)

Bagheri, Habib [Department of Chemistry, Sharif University of Technology, P.O. Box 11365-9516, Tehran (Iran, Islamic Republic of)], E-mail: Bagheri@sharif.edu; Babanezhad, Esmaeil; Khalilian, Faezeh [Department of Chemistry, Sharif University of Technology, P.O. Box 11365-9516, Tehran (Iran, Islamic Republic of)

2008-05-26

A novel amino-functionalized polymer was synthesized using 3-(trimethoxysilyl) propyl amine (TMSPA) as precursor and hydroxy-terminated polydimethylsiloxane (OH-PDMS) by sol-gel technology and coated on fused-silica fiber. The synthesis was designed in a way to impart polar moiety into the coating network. The scanning electron microscopy (SEM) images of this new coating showed the homogeneity and the porous surface structure of the film. The efficiency of new coating was investigated for headspace solid-phase microextraction (SPME) of some environmentally important chlorophenols from aqueous samples followed by gas chromatography-mass spectrometry (GC-MS) analysis. Effect of different parameters influencing the extraction efficiency such as extraction temperature, extraction time, ionic strength and pH was investigated and optimized. In order to improve the separation efficiency of phenolic compounds on chromatography column all the analytes were derivatized prior to extraction using acetic anhydride at alkaline condition. The detection limits of the method under optimized conditions were in the range of 0.02-0.05 ng mL{sup -1}. The relative standard deviations (R.S.D.) (n = 6) at a concentration level of 0.5 ng mL{sup -1} were obtained between 6.8 and 10%. The calibration curves of chlorophenols showed linearity in the range of 0.5-200 ng mL{sup -1}. The proposed method was successfully applied to the extraction from spiked tap water samples and relative recoveries were higher than 90% for all the analytes.

Relationships between acute toxicities of para nitrophenol (p-NP) and nitrobenzene (NB) to Daphnia magna and Photobacterium phosphoreum: Physicochemical properties and metabolites under anaerobic/aerobic sequentials

International Nuclear Information System (INIS)

Sponza, Delia Teresa; Kuscu, Ozlem Selcuk

2011-01-01

In this study, the acute toxicities of nitrobenzene (NB) and para nitrophenol (p-NP) were investigated in a high rate sequential anaerobic migrating blanket (AMBR)/aerobic completely stirred tank reactor (CSTR) using Microtox and Daphnia magna tests. After sequential anaerobic and aerobic treatments, the inhibitions in the Microtox bacteria decreased from an initial 78.10-48.20% and 4.00%, respectively, in wastewater containing 40.00 mg/L p-NP. The inhibitions of the influent wastewater containing 60.00 mg/L NB decreased from 72.10% to 45.30% and to 4.00% after anaerobic and aerobic treatment, respectively. The acute toxicity removals were 94% and 93% in the effluent of the whole sequential system, for p-NP and NB, respectively. The acute toxicity in the influent was dependent on the parent NB and p-NP concentrations and ons their physicochemical properties such as hydrophobicity, octanol/water partition coefficient and vapour density for both Microtox bacteria and Daphnia magna while the toxicity in the effluent of the anaerobic reactor was strongly dependent on the metabolites of p-NP (p-amino phenol, phenol, NH 4 -N) and NB (aniline) for Microtox test. This effluent was not toxic to Daphnia magna.

Changes in nuclear protein acetylation in u. v. -damaged human cells

Energy Technology Data Exchange (ETDEWEB)

Ramanathan, B.; Smerdon, M.J.

1986-07-01

We have investigated the levels of nuclear protein acetylation in u.v.-irradiated human fibroblasts. We measured the levels of acetylation in total acid-soluble nuclear proteins and observed two distinct differences between the irradiated and unirradiated (control) cells. Immediately after irradiation, there is a wave of protein hyperacetylation (i.e. a total acetylation level greater than that of unirradiated cells) that lasts for 2-6 h depending on the experimental conditions. This hyperacetylation phase is then followed by a hypoacetylation phase, lasting for many hours, and the total level of acetylation does not return to that of control cells until 24-72 h after u.v. damage. Both the magnitude and duration of each phase is dependent on the dose of u.v. light used. The wave of hyperacetylation is more pronounced at low u.v. doses (i.e. less than 5 J/m2), while the wave of hypoacetylation is more pronounced at higher u.v. doses (greater than or equal to 8 J/m2). Furthermore, the duration of each phase is prolonged when cells are exposed to 2 mM hydroxyurea. Examination of the acetylation levels of the individual nuclear proteins indicated that acetylation of the core histones follows the same pattern observed for the total acid-soluble protein fractions. Furthermore, these were the only major proteins in the total acid-soluble fraction observed to undergo the early, rapid hyperacetylation immediately following u.v. damage. Acetylation of histone H1 was negligible in both damaged and control cells, while three prominent non-histone proteins were acetylated only after long labeling times (greater than 4 h) in each case, gradually becoming hyperacetylated in the u.v.-damaged cells. These results raise the possibility that a causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells.

Impact of peptidoglycan O-acetylation on autolytic activities of the Enterococcus faecalis N-acetylglucosaminidase AtlA and N-acetylmuramidase AtlB.

Science.gov (United States)

Emirian, Aurélie; Fromentin, Sophie; Eckert, Catherine; Chau, Françoise; Dubost, Lionel; Delepierre, Muriel; Gutmann, Laurent; Arthur, Michel; Mesnage, Stéphane

2009-09-17

Autolysins are potentially lethal enzymes that partially hydrolyze peptidoglycan for incorporation of new precursors and septum cleavage after cell division. Here, we explored the impact of peptidoglycan O-acetylation on the enzymatic activities of Enterococcus faecalis major autolysins, the N-acetylglucosaminidase AtlA and the N-acetylmuramidase AtlB. We constructed isogenic strains with various O-acetylation levels and used them as substrates to assay E. faecalis autolysin activities. Peptidoglycan O-acetylation had a marginal inhibitory impact on the activities of these enzymes. In contrast, removal of cell wall glycopolymers increased the AtlB activity (37-fold), suggesting that these polymers negatively control the activity of this enzyme.

Evidence for lysine acetylation in the coat protein of a polerovirus.

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Cilia, Michelle; Johnson, Richard; Sweeney, Michelle; DeBlasio, Stacy L; Bruce, James E; MacCoss, Michael J; Gray, Stewart M

2014-10-01

Virions of the RPV strain of Cereal yellow dwarf virus-RPV were purified from infected oat tissue and analysed by MS. Two conserved residues, K147 and K181, in the virus coat protein, were confidently identified to contain epsilon-N-acetyl groups. While no functional data are available for K147, K181 lies within an interfacial region critical for virion assembly and stability. The signature immonium ion at m/z 126.0919 demonstrated the presence of N-acetyllysine, and the sequence fragment ions enabled an unambiguous assignment of the epsilon-N-acetyl modification on K181. We hypothesize that selection favours acetylation of K181 in a fraction of coat protein monomers to stabilize the capsid by promoting intermonomer salt bridge formation.

Acetyl coenzyme A synthetase is acetylated on multiple lysine residues by a protein acetyltransferase with a single Gcn5-type N-acetyltransferase (GNAT) domain in Saccharopolyspora erythraea.

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You, Di; Yao, Li-Li; Huang, Dan; Escalante-Semerena, Jorge C; Ye, Bang-Ce

2014-09-01

Reversible lysine acetylation (RLA) is used by cells of all domains of life to modulate protein function. To date, bacterial acetylation/deacetylation systems have been studied in a few bacteria (e.g., Salmonella enterica, Bacillus subtilis, Escherichia coli, Erwinia amylovora, Mycobacterium tuberculosis, and Geobacillus kaustophilus), but little is known about RLA in antibiotic-producing actinomycetes. Here, we identify the Gcn5-like protein acetyltransferase AcuA of Saccharopolyspora erythraea (SacAcuA, SACE_5148) as the enzyme responsible for the acetylation of the AMP-forming acetyl coenzyme A synthetase (SacAcsA, SACE_2375). Acetylated SacAcsA was deacetylated by a sirtuin-type NAD(+)-dependent consuming deacetylase (SacSrtN, SACE_3798). In vitro acetylation/deacetylation of SacAcsA enzyme was studied by Western blotting, and acetylation of lysine residues Lys(237), Lys(380), Lys(611), and Lys(628) was confirmed by mass spectrometry. In a strain devoid of SacAcuA, none of the above-mentioned Lys residues of SacAcsA was acetylated. To our knowledge, the ability of SacAcuA to acetylate multiple Lys residues is unique among AcuA-type acetyltransferases. Results from site-specific mutagenesis experiments showed that the activity of SacAcsA was controlled by lysine acetylation. Lastly, immunoprecipitation data showed that in vivo acetylation of SacAcsA was influenced by glucose and acetate availability. These results suggested that reversible acetylation may also be a conserved regulatory posttranslational modification strategy in antibiotic-producing actinomycetes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Hexavalent chromium-induced differential disruption of cortical microtubules in some Fabaceae species is correlated with acetylation of α-tubulin.

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Eleftheriou, Eleftherios P; Adamakis, Ioannis-Dimosthenis S; Michalopoulou, Vasiliki A

2016-03-01

The effects of hexavalent chromium [Cr(VI)] on the cortical microtubules (MTs) of five species of the Fabaceae family (Vicia faba, Pisum sativum, Vigna sinensis, Vigna angularis, and Medicago sativa) were investigated by confocal laser scanning microscopy after immunolocalization of total tubulin with conventional immunofluorescence techniques and of acetylated α-tubulin with the specific 6-11B-1 monoclonal antibody. Moreover, total α-tubulin and acetylated α-tubulin were quantified by Western immunoblotting and scanning densitometry. Results showed the universality of Cr(VI) detrimental effects to cortical MTs, which proved to be a sensitive and reliable subcellular marker for monitoring Cr(VI) toxicity in plant cells. However, a species-specific response was recorded, and a correlation of MT disturbance with the acetylation status of α-tubulin was demonstrated. In V. faba, MTs were depolymerized at the gain of cytoplasmic tubulin background and displayed low α-tubulin acetylation, while in P. sativum, V. sinensis, V. angularis, and M. sativa, MTs became bundled and changed orientation from perpendicular to oblique or longitudinal. Bundled MTs were highly acetylated as determined by both immunofluorescence and Western immunoblotting. Tubulin acetylation in P. sativum and M. sativa preceded MT bundling; in V. sinensis it followed MT derangement, while in V. angularis the two phenomena coincided. Total α-tubulin remained constant in all treatments. Should acetylation be an indicator of MT stabilization, it is deduced that bundled MTs became stabilized, lost their dynamic properties, and were rendered inactive. Results of this report allow the conclusion that Cr(VI) toxicity disrupts MTs and deranges the MT-mediated functions either by depolymerizing or stabilizing them.

EVALUATION OF THE LEAVE AND BUD DECOCTIONS PINUS HALEPENSIS MILL EFFECTS ON THE INDUCED-PHENOL RENAL TOXICITY IN WISTAR RATS

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A. Berroukche

2015-07-01

Full Text Available Pinus halepensis M. (Pinaceae has done object many indications in traditional medicine. Several studies have demonstrated a protective activity of essential oils extracted from various plant species against renal toxicity induced by chemicals in the animal model. The objective of this study is to assess the anti toxic effects of decocted leaves and buds of Pinus halepensis M. on Wistar rats initially exposed to phenol C6H5OH (180 mg / kg body weight. The results of laboratory analyzes of biochemical parameters revealed that decocted leaves and buds (250 mg / kg body weight have shown a highly significant antitoxic activity (p < 0,001. The protective effect of decocted leaves and buds were respectively expressed by a decrease in serum concentrations of biochemical markers urea ( 0,32 and 0,28 g/l and creatinine ( 121 & 13,8 g / l and electrolyte Calcium ( 89,8 & 109,5 g / l , Potassium ( 7 & 6,6 g / l and Sodium ( 130,5 & 129,6 g / l .

Isolation and characterization of a thermolysin peptide containing acetyllysine from enzymatically acetylated f2al histone

International Nuclear Information System (INIS)

Horiuchi, Kentaro; Fujimoto, Daisaburo

1973-01-01

Previous studies (vol. 72, 433, '72) in this laboratory showed that histone acetylase in the cytosol of calf thymus introduced acetyl groups primarily into the epsilon-amino groups of lysine residues in a histone fraction, f2al. In an attempt to examine the site of acetylation in f2al by the enzyme, 14 C-acetylated f2al was isolated and digested by thermolysin. A radioactive peptide, which accounted for 50 - 60% of the total radioactivity, was obtained from the thermolysin digest and identified as the fragment containing amino acid residues 10-21. It appears, therefore, that the major sites of acetylation by the enzyme are the lysine 12 or 16 or both, which are known to be acetylated in vivo. It was also shown that the peptide was not deacetylated by histone deacetylase, in contrast with the whole f2al molecule. (author)

Cigarette Smoking, N-Acetyltransferase 2 Acetylation Status, and Bladder Cancer Risk

DEFF Research Database (Denmark)

Marcus, P.M.; Hayes, R.B.; Vineis, P.

2000-01-01

Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder...... cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize...... results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used...

Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A & B in workers exposed to cadmium at cadmium plating

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Rajan BK

2007-07-01

Full Text Available Abstract Objective The present study was carried out to determine the effect of cadmium exposure on Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B in workers exposed at cadmium plating. Methods 50 subjects using cadmium during cadmium plating formed the study group. An equal number of age-sex matched subjects working in administrative section formed the control group. Urinary cadmium levels were determined by using a flameless atomic absorption spectrophotometer. Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B were determined by using spectrophotmetric method. Results A significant increase of urinary total N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were noted in study as compared to controls. The levels of urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were positively and significantly correlated with cadmium levels in urine. Multiple regression analysis was used to assess the effect of urinary cadmium or life style confounding factors (age, BMI, smoking and alcohol consumption on urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B. The analysis showed that the study subjects who had urine cadmium levels greater than 5 μg/g of creatinine, work duration >15 years, smoking and body mass index variables were significantly associated with urinary total N-acetyl-beta -D-glucosaminidase but not on isoenzymes A&B. Conclusion The results presented in this study shows that the increased levels of urinary N-acetyl-beta -D-glucosaminidase observed in cadmium-exposed workers could be used as biomarkers for suggesting preventive measure.

Alpha-amino acid derivatives and alpha-fluoro ketones by enantioselective decarboxylation

OpenAIRE

Baur, Markus A.

2003-01-01

Die Methode der enantioselektiven Decarboxylierung wurde angewendet, um Enantiomeren-angereicherte alpha-Aminosäurederivate und alpha-Fluorketone zu erhalten. Als Substrate wurden 2-N-Acetylamino-2-alkylmalonsäuremonoethylester beziehungsweise beta-Keto-benzylester verwendet. China-Alkaloide und Derivate davon wurden als Katalysatoren eingesetzt. Die besten erhaltenen Ergebnisse waren N-Acetyl-L-phenylalaninethylester mit 70% Enantiomerenüberschuß unter Verwendung der katalytisch aktiven Base...

Technetium-99m labelled N,N-ethyldithiocarbamate, a non-polar complex with slow hepatic clearance

International Nuclear Information System (INIS)

Pojer, P.M.; Baldas, J.

1980-05-01

A sup(99m)Tc-N,N-diethyldithiocarbamate (DDC) complex was prepared using formamidine sulphinic acid as the reducing agent for pertechnetate sup(99m) Tc. The complex was found to be non-polar. In mice the complex localised in the liver and intestines. Urinary excretion was very low and hepatic clearance relatively slow

Evaluation of di-amino phenol substituted EDTA for use in radiolabelling proteins with 64Cu

International Nuclear Information System (INIS)

Schmidt, P.F.; Smith, S.V.; DiBartolo, N.M.

1996-01-01

This study involves a high yielding synthesis of a novel di-amino-phenol substituted EDTA (DAHA-EDTA) ligand and its radiolabelling chemistry with 64 Cu produced at the National Medical Cyclotron (NMC). High activity levels (up to 59.2 GBq EOB) of 64 Cu is co-produced during the production of 67 Ga from enriched 68 Zn. Waste eluent from the NMC 67 Ga production was evaporated to dryness and found to contain by products such as 57 Ni, 57 Co, 64 Cu, 67 Cu and 55 Co. A new method involving low acid concentration aqueous/organic mixtures with an anion exchange (AG 1-X8, BioRad) have been used to isolate the carrier-free 64 Cu. The specific activity of the 64 Cu (5 x 10 14 Bq/g) was found to be higher than that produce by Australian radioisotopes (ARI). The synthesis of the ligand involves the refluxing of EDTA anhydride in the presence of 4-nitro-2-amino-phenol in acetonitrile to produce the di-nitro derivative (DNHA- EDTA) in > 95% yield. The DNHA-EDTA is then reduced in the presence of activated palladium charcoal with sodium borohydride under an inert atmosphere at room temperature. The reaction mixture was acidified and the catalyst removed to obtain the final product, DAHA-EDTA. Labelling of proteins (B72.3, DD-3B6/22 and streptavidin) has been achieved with the DAHA-EDTA ligand. The reaction mixture is left to incubate for 1 h at 37 deg C and radiolabelled protein is then isolated using size exclusion chromatography

Acute toxicity of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives

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D. M. Danilchenko

2017-09-01

Full Text Available The purpose of our work was the further exploration of the new 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives’ acute toxicity, setting some patterns of alkyl substituents influence by the Sulfur atom on the acute toxicity. Research materials and methods. In this study we used first time synthesized 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole-3-thione derivatives. Acute toxicity was conducted on white rats weighing 160–250 g, which were injected once intraperitoneally with the investigated substances. The rats were received from the nursery of the Pharmacology and Toxicology Institute of Ukraine Medical Sciences Academy. The animals were kept on a standard diet with natural light mode "day-night". Results and their discussion. After the acute toxicity studies in a group of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkyl derivatives it was found that among all studied structures the most toxic was 2e, LD50 of which was 263 mg/kg, and the least toxic compound was 2a, LD50 of which was 1570 mg/kg, that belongs to the V toxicity class. After comparing the acute toxicity of well-known antimycotic agent fluconazole with the studied compounds it can be argued that most compounds are less toxic than the comparison drug fluconazole with the index of LD50 ˃320 mg/kg. It was found that the transition in a group from butyl to decyl, octyl, ventyl, propyl, nonyl and heptyl substituents in the molecule of 3-alkylthio 5-(furan-2-yl-4-amino-4H-1,2,4-triazole is accompanied by the toxicity increasing. Speaking about the 5-(2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkylthio derivatives we can find that this dependence is observed in a number from propyl, pentyl, nonil, butyl, heksyl, octyl and heptyl hydrocarbon chains. Conclusions. The investigated 3-alkylthio 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole derivatives belong to the IV-V toxicity class. The toxicity of 5

Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo

Energy Technology Data Exchange (ETDEWEB)

Nouraei, Negin; Zarger, Lauren; Weilnau, Justin N.; Han, Jimin; Mason, Daniel M.; Leak, Rehana K., E-mail: leakr@duq.edu

2016-04-01

The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 μg) and administered NAC intraperitoneally (100 mg/kg). NAC-treated animals exhibited higher levels of the dopaminergic terminal marker tyrosine hydroxylase (TH) in the striatum 10d after 6-OHDA. As TH expression is subject to stress-induced modulation, we infused the tracer FluoroGold into the striatum to retrogradely label nigrostriatal projection neurons. As expected, nigral FluoroGold staining and cell counts of FluoroGold{sup +} profiles were both more sensitive measures of nigrostriatal degeneration than measurements relying on TH alone. However, NAC failed to protect dopaminergic neurons 3 weeks following 6-OHDA, an effect verified by four measures: striatal TH levels, nigral TH levels, nigral TH{sup +} cell counts, and nigral FluoroGold levels. Some degree of mild toxicity of FluoroGold and NAC was evident, suggesting that caution must be exercised when relying on FluoroGold as a neuron-counting tool and when designing experiments with long-term delivery of NAC—such as clinical trials on patients with chronic disorders. Finally, the strengths and limitations of the tools used to define nigrostriatal degeneration are discussed. - Highlights: • N-acetyl cysteine (NAC) was injected into animals infused with the toxicant 6-OHDA. • Retrograde tracing with FluoroGold was used to define nigrostriatal cell loss. • Infrared Odyssey imaging and cell counts were used to screen for nigral cell loss. • NAC protected transiently against 6-OHDA but this effect waned over time. • Mildly

Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.

Science.gov (United States)

Jeng, J H; Wang, Y J; Chang, W H; Wu, H L; Li, C H; Uang, B J; Kang, J J; Lee, J J; Hahn, L J; Lin, B R; Chang, M C

2004-01-01

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (delta Psim) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

Science.gov (United States)

King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

2011-10-13

Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

Validation of transport measurements in skeletal muscle with N-13 amino acids using a rabbit isolated hindlimb model

International Nuclear Information System (INIS)

Conlon, K.C.; Bading, J.R.; DiResta, G.R.; Corbally, M.T.; Gelbard, A.S.; Brennan, M.F.

1989-01-01

The authors are studying the transport of C-11 and N-13 labeled amino acids in tumor-bearing rabbits to determine the role of amino acid transport in the pathogenesis of muscle wasting in cancer. To validate a new, in vivo, method for measuring transport in skeletal muscle with these compounds, an isolated hindlimb model was developed in rabbits. The limb was perfused with a non-recirculating, normothermic, constant pressure system and a cell-free perfusate. Hemodynamic and metabolic parameters were measured during the first 75 min. of perfusion and found to remain normal and stable. Flow varied directly with perfusion pressure over the normal range of resting flows in the intact rabbit hindlimb. Time-activity curves (TAC's) were recorded from the medial thigh following bolus co-injection of L-[amide N-13] glutamine or N-13 L-glutamate with Tc-99m human serum albumin (HSA) into the femoral artery. Regional plasma flow was determined from the Tc-99m data

In silico prediction of toxicity of phenols to Tetrahymena pyriformis by using genetic algorithm and decision tree-based modeling approach.

Science.gov (United States)

Abbasitabar, Fatemeh; Zare-Shahabadi, Vahid

2017-04-01

Risk assessment of chemicals is an important issue in environmental protection; however, there is a huge lack of experimental data for a large number of end-points. The experimental determination of toxicity of chemicals involves high costs and time-consuming process. In silico tools such as quantitative structure-toxicity relationship (QSTR) models, which are constructed on the basis of computational molecular descriptors, can predict missing data for toxic end-points for existing or even not yet synthesized chemicals. Phenol derivatives are known to be aquatic pollutants. With this background, we aimed to develop an accurate and reliable QSTR model for the prediction of toxicity of 206 phenols to Tetrahymena pyriformis. A multiple linear regression (MLR)-based QSTR was obtained using a powerful descriptor selection tool named Memorized_ACO algorithm. Statistical parameters of the model were 0.72 and 0.68 for R training 2 and R test 2 , respectively. To develop a high-quality QSTR model, classification and regression tree (CART) was employed. Two approaches were considered: (1) phenols were classified into different modes of action using CART and (2) the phenols in the training set were partitioned to several subsets by a tree in such a manner that in each subset, a high-quality MLR could be developed. For the first approach, the statistical parameters of the resultant QSTR model were improved to 0.83 and 0.75 for R training 2 and R test 2 , respectively. Genetic algorithm was employed in the second approach to obtain an optimal tree, and it was shown that the final QSTR model provided excellent prediction accuracy for the training and test sets (R training 2 and R test 2 were 0.91 and 0.93, respectively). The mean absolute error for the test set was computed as 0.1615. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the Effects of S-Allyl-L-cysteine, S-Methyl-L-cysteine, trans-S-1-Propenyl-L-cysteine, and Their N-Acetylated and S-Oxidized Metabolites on Human CYP Activities.

Science.gov (United States)

Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

2016-01-01

Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Allicin, a major component of garlic, inhibited CYP1A2 and CYP3A4 activity by 21-45% at 0.03 mM. In contrast, a CYP2C9-catalyzed reaction was enhanced by up to 1.9 times in the presence of allicin at 0.003-0.3 mM. SAC, SMC, and S1PC had no effect on the activities of the five isoforms, except that S1PC inhibited CYP3A4-catalyzed midazolam 1'-hydroxylation by 31% at 1 mM. The N-acetylated metabolites of the three compounds inhibited the activities of several isoforms to a varying degree at 1 mM. N-Acetyl-S-allyl-L-cysteine and N-acetyl-S-methyl-L-cysteine inhibited the reactions catalyzed by CYP2D6 and CYP1A2, by 19 and 26%, respectively, whereas trans-N-acetyl-S-1-propenyl-L-cysteine showed weak to moderate inhibition (19-49%) of CYP1A2, 2C19, 2D6, and 3A4 activities. On the other hand, both the N-acetylated and S-oxidized metabolites of SAC, SMC, and S1PC had little effect on the reactions catalyzed by the five isoforms. These results indicated that SAC, SMC, and S1PC have little potential to cause drug-drug interaction due to CYP inhibition or activation in vivo, as judged by their minimal effects (IC 50 >1 mM) on the activities of five major isoforms of human CYP in vitro.

Minimally Adhesive, Advanced Non-toxic Coatings of Dendrimeric Catalysts in Sol-Gel Matrices

Science.gov (United States)

2015-10-19

Catalysts in Sol -Gel Matrices 5a. CONTRACT NUMBER 5b. GRANT NUMBER N00014-09-1-0217 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Detty, Michael R. 5d...Technical Report for ONR N00014-09-1-0217 Minimally Adhesive, Advanced Non-toxic Coatings of Dendrimeric Catalysts in Sol -Gel Matrices Michael R. Detty, PI...Environmentally benign sol -gel antifouling and foul-releasing coatings. Ace. Chem. Res. 2014, 47, 678-687. 11) Alberto, E. E.; Müller, L. M

Neural-network analysis of the vibrational spectra of N-acetyl L-alanyl N '-methyl amide conformational states

DEFF Research Database (Denmark)

Bohr, Henrik; Frimand, Kenneth; Jalkanen, Karl J.

2001-01-01

Density-functional theory (DFT) calculations utilizing the Becke 3LYP hybrid functional have been carried out for N-acetyl L-alanine N'-methylamide and examined with respect to the effect of water on the structure, the vibrational frequencies, vibrational absorption (VA), vibrational circular dic...

The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue

Directory of Open Access Journals (Sweden)

Smith Milton

2008-06-01

Full Text Available Abstract Background Sulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD, is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES, are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO production via suppression of inducible NO synthase (iNOS protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels. NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and

Estimating the contribution of N-sulfocarbamoyl paralytic shellfish toxin analogs GTX6 and C3+4 to the toxicity of mussels (Mytilus galloprovincialis) over a bloom of Gymnodinium catenatum.

Science.gov (United States)

Costa, Pedro Reis; Moita, Teresa; Rodrigues, Susana Margarida

2014-01-01

Gymnodinium catenatum, a dinoflagellate species with a global distribution, is known to produce paralytic shellfish poisoning (PSP) toxins. The profile of toxins of G. catenatum is commonly dominated by sulfocarbamoyl analogs including the C3+4 and GTX6, which to date has no commercial certified reference materials necessary for their quantification via chemical methods, such as liquid chromatography. The aim of this study was to assess the presence of C3+4 and GTX6 and their contribution to shellfish toxicity. C3+4 and GTX6 were indirectly quantified via pre-column oxidation liquid chromatography with fluorescence detection after hydrolysis conversion into their carbamate analogs. Analyses were carried out in mussel samples collected over a bloom of G. catenatum (>63×10 3 cellsl -1 ) in Aveiro lagoon, NW Portuguese coast. Concentration levels of sulfocarbamoyl toxin analogs were two orders of magnitude higher than decarbamoyl toxins, which were in turn one order of magnitude higher than carbamoyl toxins. Among the sulfocarbamoyl toxins, C1+2 were clearly the dominant compounds, followed by C3+4 and GTX6. The least abundant sulfocarbamoyl toxin was GTX5. The most important compounds in terms of contribution for sample toxicity were C1+2, which justified 26% of the PSP toxicity. The lesser abundant dcSTX constitutes the second most important compound with similar % of toxicity to C1+2, C3+4 and GTX6 were responsible for approximately 11% and 13%, respectively. The median of the sum of C3+4 and GTX6 was 27%. These levels reached a maximum of 60% as was determined for the sample collected closest to the G. catenatum bloom. This study highlights the importance of these low potency PSP toxin analogs to shellfish toxicity. Hydrolysis conversion of C3+4 and GTX6 is recommended for determination of PSP toxicity when LC detection methods are used for PSP testing in samples exposed to G. catenatum. Copyright © 2013 Elsevier B.V. All rights reserved.

Amino acid chirality breaking by N-phosphorylation

International Nuclear Information System (INIS)

Zhao Yufen; Yan Qingjin.

1995-01-01

The chirality breaking of amino acid is a focus issue in the origin of life. For chemists, there are some interesting chemical approaches to solve the symmetry breaking problem. Our previous experiments indicated that when amino acids were phosphorylated, there were many bio-mimic reactions happened. In this paper, it was found that there had significant difference between the N-phosphoryl L- and D- amino acids such as serine and threonine. The optical rotation tracing experiments of the racemic N-phosphoamino acids also showed the similar results. The chirality breaking of amino acids by N-phosphorylation was a novel phenomena. (author). 3 refs, 1 fig. Abstract only

In vivo labelling of acetyl-aspartyl peptides in mouse brain from intracranially and intracranially and intraperitoneally administered acetyl-L-[U-14C]aspartate

International Nuclear Information System (INIS)

Sinichkin, A.; Sterri, S.; Edminson, P.D.; Reichelt, K.L.; Kvamme, E.

1977-01-01

Following intracranial and intraperitoneal injection of acetyl-L-[U- 14 C]aspartate into mice about 5% and 0.7% of the radioactivity, respectively, was recovered from the brain after 30 min. On chromatographic separation of the cationic and anionic compounds on a Dowex 50 column, the former fraction contained about 60% of the radioactivity, predominantly as labelled asparate and glutamate. The anionic compounds, containing 20% of the labelled compounds, were fractionated in several chromatographic systems and resolved into a great variety of labelled peptidic compounds of which five acetyl-[U 14 ]aspartyl peptides, containing two to four amino acids, were purified. One of these, acetyl-aspartyl glutamine, has not previously been found in brain. (author)

Phenolic acids and flavonoids of peanut by-products: Antioxidant capacity and antimicrobial effects.

Science.gov (United States)

de Camargo, Adriano Costa; Regitano-d'Arce, Marisa Aparecida Bismara; Rasera, Gabriela Boscariol; Canniatti-Brazaca, Solange Guidolin; do Prado-Silva, Leonardo; Alvarenga, Verônica Ortiz; Sant'Ana, Anderson S; Shahidi, Fereidoon

2017-12-15

Peanut skin (PS) and meal from dry-blanched peanuts (MDBP) were evaluated as sources of phenolic compounds. PS rendered the highest total phenolic content, antioxidant capacity towards ABTS radical cation, DPPH and hydroxyl radicals as well as reducing power. Phenolic acids were present in PS and MDBP whereas proanthocyanidins and monomeric flavonoids were found only in PS as identified by HPLC-DAD-ESI-MS n . Procyanidin-rich extracts prevented oxidation in non-irradiated and gamma-irradiated fish model system. Both extracts inhibited the growth of gram-positive (Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Geobacillus stearothermophilus) and gram-negative bacteria (Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli). Regardless of the strain, phenolic acid-rich extracts showed the lowest minimum inhibitory capacity (MIC); therefore presenting higher antibacterial effect. The MIC of phenolic acid-rich extracts (24-49μgphenolics/mL) was higher but comparable to Ampicillin (10μg/mL). Thus, phenolics in PS and MDBP may serve as antioxidants and antimicrobial compounds. Copyright © 2017. Published by Elsevier Ltd.

Synthesis, evaluation, and mechanism of N,N,N-trimethyl-D-glucosamine-(1→4)-chitooligosaccharides as selective inhibitors of glycosyl hydrolase family 20 β-N-acetyl-D-hexosaminidases.

Science.gov (United States)

Yang, You; Liu, Tian; Yang, Yongliang; Wu, Qingyue; Yang, Qing; Yu, Biao

2011-02-11

GH20 β-N-acetyl-D-hexosaminidases are enzymes involved in many vital processes. Inhibitors that specifically target GH20 enzymes in pests are of agricultural and economic importance. Structural comparison has revealed that the bacterial chitindegrading β-N-acetyl-D-hexosaminidases each have an extra +1 subsite in the active site; this structural difference could be exploited for the development of selective inhibitors. N,N,Ntrimethyl-D-glucosamine (TMG)-chitotriomycin, which contains three GlcNAc residues, is a natural selective inhibitor against bacterial and insect β-N-acetyl-D-hexosaminidases. However, our structural alignment analysis indicated that the two GlcNAc residues at the reducing end might be unnecessary. To prove this hypothesis, we designed and synthesized a series of TMG-chitotriomycin analogues containing one to four GlcNAc units. Inhibitory kinetics and molecular docking showed that TMG-(GlcNAc)(2), is as active as TMG-chitotriomycin [TMG-(GlcNAc)(3)]. The selective inhibition mechanism of TMG-chitotriomycin was also explained. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal aromatic Claisen rearrangement and Strecker reaction of alkyl(allyl-aryl ethers under green reaction conditions: Efficient and clean preparation of ortho-allyl phenols (naphthols and alkyl(allyloxyarene-based γ-amino nitriles

Directory of Open Access Journals (Sweden)

Kheila N. Silgado-Gómez

2017-11-01

Full Text Available Chemical transformations of 13 diverse allyl(alkyl-aryl ethers, easily prepared using Williamson reaction of different hydroxyarenes and allyl bromide and alkyl (n-butyl, n-octyl bromides, were studied. Thermal aromatic Claisen rearrangement of allyl-aryl ethers to obtain ortho-allyl phenols (naphthols employing propylene carbonate as a nontoxic and biodegradable solvent was described for the first time. The use of this green solvent allowed to enhance notably product yields and reduce significantly the reaction time comparing with the use of 1,2-dichlorobenzene, toxic solvent, which is traditionally employed in this type of Claisen rearrangement. Three-component Strecker reaction of selected alkyl(allyl-aryl ethers with formyl function on aryl fragment and, piperidine and potassium cyanide in the presence of sulfuric acid supported on silica gel (SSA, SiO2-O-SO3H under mild reaction conditions was used in the preparation of new γ-amino nitriles, analogues of alkaloid girgensohnine [2-(4-hydroxyphenyl-2-(piperidin-1-ylacetonitrile], a perspective biological model in the search for new insecticidal agrochemicals against Aedes aegypti. The use of SSA, an inexpensive and reusable solid catalyst, allowed to obtain new series of 2-[4-alkyl(allyloxyphenyl]-2-(piperidin-1-ylacetonitriles in short time at room temperature with good yields.

Antioxidant capacities, phenolic profile and cytotoxic effects of saxicolous lichens from trans-Himalayan cold desert of Ladakh.

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Jatinder Kumar

Full Text Available Fourteen saxicolous lichens from trans-Himalayan Ladakh region were identified by morpho-anatomical and chemical characteristics. The n-hexane, methanol and water extracts of the lichens were evaluated for their antioxidant capacities. The lichen extracts showing high antioxidant capacities and rich phenolic content were further investigated to determine their cytotoxic activity on human HepG2 and RKO carcinoma cell lines. The ferric reducing antioxidant power (FRAP, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS, 1,1-diphenyl-2-picrylhydrazyl (DPPH and nitric oxide (NO radical scavenging capacities and β-carotene-linoleic acid bleaching property exhibited analogous results where the lichen extracts showed high antioxidant action. The lichen extracts were also found to possess good amount of total proanthocyanidin, flavonoid and polyphenol. The methanolic extract of Lobothallia alphoplaca exhibited highest FRAP value. Methanolic extract of Xanthoparmelia stenophylla showed the highest ABTS radical scavenging capacity. The n-hexane extract of Rhizoplaca chrysoleuca exhibited highest DPPH radical scavenging capacity. Highest antioxidant capacity in terms of β-carotene linoleic acid bleaching property was observed in the water extract of Xanthoria elegans. Similarly, Melanelia disjuncta water extract showed highest NO scavenging capacity. Among n-hexane, methanol and water extracts of all lichens, the methanolic extract of Xanthoparmelia mexicana showed highest total proanthocyanidin, flavonoid and polyphenol content. From cytotoxic assay, it was observed that the methanolic extracts of L. alphoplaca and M. disjuncta were exhibiting high cytotoxic effects against cancer cell growth. Similarly, the water extract of Dermatocarpon vellereum, Umbilicaria vellea, X. elegans and M. disjuncta and the methanolic extract of M. disjuncta and X. stenophylla were found to possess high antioxidant capacities and were non-toxic and

METHODS OF REDUCTION OF FREE PHENOL CONTENT IN PHENOLIC FOAM

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Bruyako Mikhail Gerasimovich

2012-12-01

method aimed at reduction of toxicity of phenolic foams consists in the introduction of a composite mixture of chelate compounds. Raw materials applied in the production of phenolic foams include polymers FRB-1A and VAG-3. The aforementioned materials are used to produce foams FRP-1. Introduction of 1% aluminum fluoride leads to the 40% reduction of the free phenol content in the foam. Introduction of crystalline zinc chloride accelerates the foaming and curing of phenolic foams. The technology that contemplates the introduction of zeolites into the mixture includes pre-mixing with FRB -1A and subsequent mixing with VAG-3; thereafter, the composition is poured into the form, in which the process of foaming is initiated. The content of free phenol was identified using the method of UV spectroscopy. The objective of the research was to develop methods of reduction of the free phenol content in the phenolic foam.

Identification and characterization of AckA-dependent protein acetylation in Neisseria gonorrhoeae.

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Deborah M B Post

Full Text Available Neisseria gonorrhoeae, the causative agent of gonorrhea, has a number of factors known to contribute to pathogenesis; however, a full understanding of these processes and their regulation has proven to be elusive. Post-translational modifications (PTMs of bacterial proteins are now recognized as one mechanism of protein regulation. In the present study, Western blot analyses, with an anti-acetyl-lysine antibody, indicated that a large number of gonococcal proteins are post-translationally modified. Previous work has shown that Nε-lysine acetylation can occur non-enzymatically with acetyl-phosphate (AcP as the acetyl donor. In the current study, an acetate kinase mutant (1291ackA, which accumulates AcP, was generated in N. gonorrhoeae. Broth cultures of N. gonorrhoeae 1291wt and 1291ackA were grown, proteins extracted and digested, and peptides containing acetylated-lysines (K-acetyl were affinity-enriched from both strains. Mass spectrometric analyses of these samples identified a total of 2686 unique acetylation sites. Label-free relative quantitation of the K-acetyl peptides derived from the ackA and wild-type (wt strains demonstrated that 109 acetylation sites had an ackA/wt ratio>2 and p-values <0.05 in at least 2/3 of the biological replicates and were designated as "AckA-dependent". Regulated K-acetyl sites were found in ribosomal proteins, central metabolism proteins, iron acquisition and regulation proteins, pilus assembly and regulation proteins, and a two-component response regulator. Since AckA is part of a metabolic pathway, comparative growth studies of the ackA mutant and wt strains were performed. The mutant showed a growth defect under aerobic conditions, an inability to grow anaerobically, and a defect in biofilm maturation. In conclusion, the current study identified AckA-dependent acetylation sites in N. gonorrhoeae and determined that these sites are found in a diverse group of proteins. This work lays the foundation for

[Production, absorption and excretion of phenols in intestinal obstruction].

Science.gov (United States)

Kawamoto, M

1986-11-01

In intestinal obstruction, phenols were produced in the distended loop proximal to obstruction by enteric bacteria. Clinically, in 17 cases of non-strangulated intestinal obstruction, phenols were detected in 15 cases and mean concentration of phenols was 4.2 +/- 9.7 micro g/ml(mean +/- 1 SD). In the fraction of phenols, p-cresol was detected in 15 cases and mean concentration was 3.8 +/- 7.7 and phenol was detected in 4 cases and mean concentration was 0.5 +/- 2.6. Phenols were decreased as clinical improvement of intestinal obstruction. Enteric bacteria in enteric juice ranged from 10(4) to 10(10)/ml and its change paralleled to phenols concentration. Mean urinary concentration of phenols in intestinal obstruction was increased to 297 +/- 415 mg/day compared to control (less than 50 mg/day). Its change also paralleled to phenols concentration in enteric juice. Closed ileal loop was made in dogs and phenols were infused in the loop. Phenols were increased in the portal vein 5 min after the infusion and in the femoral vein 60 min after the infusion. Phenols, which was thought to be toxic to the host, were proved to be produced in the distended intestine and excreted from the kidney.

Mass energy-absorption coefficients and average atomic energy-absorption cross-sections for amino acids in the energy range 0.122-1.330 MeV

Energy Technology Data Exchange (ETDEWEB)

More, Chaitali V., E-mail: chaitalimore89@gmail.com; Lokhande, Rajkumar M.; Pawar, Pravina P., E-mail: pravinapawar4@gmail.com [Department of physics, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004 (India)

2016-05-06

Mass attenuation coefficients of amino acids such as n-acetyl-l-tryptophan, n-acetyl-l-tyrosine and d-tryptophan were measured in the energy range 0.122-1.330 MeV. NaI (Tl) scintillation detection system was used to detect gamma rays with a resolution of 8.2% at 0.662 MeV. The measured attenuation coefficient values were then used to determine the mass energy-absorption coefficients (σ{sub a,en}) and average atomic energy-absorption cross sections (μ{sub en}/ρ) of the amino acids. Theoretical values were calculated based on XCOM data. Theoretical and experimental values are found to be in good agreement.

A kinetic and mechanistic study on the oxidation of l-methionine and N-acetyl l-methionine by cerium(IV) in sulfuric acid medium

OpenAIRE

T. Sumathi; P. Shanmugasundaram; G. Chandramohan

2016-01-01

The kinetics of oxidation of l-methionine and N-acetyl l-methionine by Ce(IV) in sulfuric acid–sulfate media in the range of 288.1–298.1 K has been investigated. The major oxidation products of methionine and N-acetyl l-methionine have been identified as methionine sulfoxide and N-acetyl methionine sulfoxide. The major oxidation products have been confirmed by qualitative analysis and boiling point. The reaction was first order with respect to l-methionine, N-acetyl l-methionine and Ce(IV). I...

Electrokinetic transport behavior of phenol in upper Permian soils

Energy Technology Data Exchange (ETDEWEB)

Haus, R.; Zorn, R.; Czurda, K.; Ruthe, H. [Dept. of Applied Geology, Univ. Karlsruhe (Germany)

2001-07-01

Electrokinetic experiments with upper Permian, phenol contaminated soils ('Solaris'-area Chemnitz) were performed. Bench scale results show the successful removal of phenol. The developing soil-pH during electroremediation tests is found to affect the transport behavior of phenol strongly. If buffer solutions are used at the electrode compartments, phenol could be removed from the soils. By neutralizing the generating hydrogen ions at the anode reservoir the hydroxyl ions developing at the cathode by the electrolysis of water enter the soil and propagate to the anode by increasing the soil pH. The pH dependent dehydroxylation of phenol promotes the electromigration of negative charged phenolate ions from the cathode to the anode. At the anode the coupling of phenoxyl-radicals supports the formation of non toxic, water insoluble polyoxyphenylene by electro-polymerization. In the case of buffering the pH at the cathode uncharged phenol is transported by electroosmosis from the anode to the cathode because of the nonexisting base front and the unhindered production of hydrogen ions at the anode. (orig.)

A novel ion-exclusion chromatography-mass spectrometry method to measure concentrations and cycling rates of carbohydrates and amino sugars in freshwaters.

Science.gov (United States)

Horňák, Karel; Pernthaler, Jakob

2014-10-24

The concentrations of free neutral carbohydrates and amino sugars were determined in freshwater samples of distinct matrix complexity, including meso-, eu- and dystrophic lakes and ponds, using high-performance ion-exclusion chromatography (HPIEC) coupled to mass spectrometry (MS). In contrast to other methods, our approach allowed the quantification of free neutral carbohydrates and amino sugars at low nM concentrations without derivatization, de-salting or pre-concentration. New sample preparation procedures were applied prior to injection employing syringe and hollow fiber filtration. Analytes were separated on a strong cation exchange resin under 100% aqueous conditions using 0.1% formic acid as a mobile phase. To minimize background noise in MS, analytes were detected in a multiple reaction monitoring scan mode with double ion filtering. Detection limits of carbohydrates and amino sugars ranged between 0.2 and 2nM at a signal-to-noise ratio >5. Error ranged between 1 and 12% at 0.5-500nM levels. Using a stable isotope dilution approach, both the utilization and recycling of glucose in Lake Zurich was observed. In contrast, N-acetyl-glucosamine was equally rapidly consumed but there was no visible de novo production. The simple and rapid sample preparation makes our protocol suitable for routine analyses of organic compounds in freshwater samples. Application of stable isotope tracers along with accurate measures of carbohydrate and amino sugar concentrations enables novel insights into the compound in situ dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

High specific activity N-Acetyl-3H-α-Aspartyl- L-Glutamic at micro mole scale

International Nuclear Information System (INIS)

Suarez, C.

1984-01-01

High specific activity N-Acetyl-3 H - α -Aspartyl-I-Glutamic acid at micro mole scale in prepared acetylating L- α -Aspartyl-L-glutamic with 3 H -acetic anhydride in re distilled toluene. The product le purified through cationic and anionic columns. The radiochemical purity as determined by thin-layer chromatography is greater then 99% at the time preparation. (Author) 5 refs

Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine

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Andrew J. O’Leary

2018-01-01

Full Text Available Oxygen deficit (hypoxia is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2 = 0.10 with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.. Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS were determined. Hypoxia caused pronounced diaphragm muscle weakness, unrelated to increased respiratory muscle work. Hypoxia increased diaphragm HIF-1α protein content and activated MAPK, mTOR, Akt, and FoxO3a signalling pathways, largely favouring protein synthesis. Hypoxia increased diaphragm lipid peroxidation, indicative of oxidative stress. FoxO3 and MuRF-1 gene expression were increased. Diaphragm 20S proteasome activity and muscle fibre size and distribution were unaffected by acute hypoxia. Pretreatment with N-acetyl cysteine substantially enhanced cell survival signalling, prevented hypoxia-induced diaphragm oxidative stress, and prevented hypoxia-induced diaphragm dysfunction. Hypoxia is a potent driver of diaphragm weakness, causing myofibre dysfunction without attendant atrophy. N-acetyl cysteine protects the hypoxic diaphragm and may have application as a potential adjunctive therapy.

A GC-ECD method for estimation of free and bound amino acids, gamma-aminobutyric acid, salicylic acid, and acetyl salicylic acid from Solanum lycopersicum (L.).

Science.gov (United States)

Meher, Hari Charan; Gajbhiye, Vijay T; Singh, Ghanendra

2011-01-01

A gas chromatograph with electron capture detection method for estimation of selected metabolites--amino acids (free and bound), gamma-aminobutyric acid (GABA), salicylic acid (SA), and acetyl salicylic acid (ASA) from tomato--is reported. The method is based on nitrophenylation of the metabolites by 1-fluoro-2, 4-dinitrobenzene under aqueous alkaline conditions to form dinitophenyl derivatives. The derivatives were stable under the operating conditions of GC. Analysis of bound amino acids comprised perchloric acid precipitation of protein, alkylation (carboxymethylation) with iodoacetic acid, vapor-phase hydrolysis, and derivatization with 1-fluoro-2,4-dinitrobenzene in that order. The metabolites were resolved in 35 min, using a temperature-programmed run. The method is rapid, sensitive, and precise. It easily measured the typical amino acids (aspartate, asparagine, glutamate, glutamine, alanine, leucine, lysine, and phenylalanine) used for identification and quantification of a protein, resolved amino acids of the same mass (leucine and isoleucine), satisfactorily measured sulfur amino acid (methionine, cystine, and cysteine), and quantified GABA, SA, and ASA, as well. The developed method was validated for specificity, linearity, and precision. It has been applied and recommended for estimation of 25 metabolites from Solanum lycopersicum (L.).

Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

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Madácsi Ramóna

2010-06-01

Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

Water-Soluble N-Acetyl-L-cysteine-Capped CdTe Quantum Dots Application for Hg(II Detection

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Tianming Yang

2013-01-01

Full Text Available A simple, rapid, and specific method for Hg(II detection has been proposed based on the fluorescence change of N-acetyl-L-cysteine-capped CdTe quantum dots (QDs. The presence of Hg(II ions could quench the fluorescence of QDs at 565 nm and meanwhile produce new peak in 700–860 nm wavelength range. The linear response range is 20–430 nM with the detection limit at 8.0 nM Hg(II. It was found that the position of the new peak was irrelevant to the size of QDs. Furthermore, the mechanism of the quenching of QDs fluorescence by Hg(II and the appearance of new peak in near-infrared area were also discussed and deduced through ultraviolet absorption spectrum, fluorescence spectrum, and X-ray photoelectron spectrum.

ISOLATION AND CHARACTERIZATION OF A MOLYBDENUM-REDUCING, PHENOL- AND CATECHOL-DEGRADING PSEUDOMONAS PUTIDA STRAIN AMR-12 IN SOILS FROM EGYPT

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M. Abd. AbdEl-Mongy

2016-02-01

Full Text Available Sites contaminated with both heavy metals and organic xenobiotic pollutants warrants the effective use of either a multitude of bacterial degraders or bacteria having the capacity to detoxify numerous toxicants simultaneously. A molybdenum-reducing bacterium with the capacity to degrade phenolics is reported. Molybdenum (sodium molybdate reduction was optimum between pH 6.0 and 7.0 and between 20 and 30 °C. The most suitable electron donor was glucose. A narrow range of phosphate concentrations between 5.0 and 7.5 mM was required for optimal reduction, while molybdate between 20 and 30 mM were needed for optimal reduction. The scanning absorption spectrum of the molybdenum blue produced indicated that Mo-blue is a reduced phosphomolybdate. Molybdenum reduction was inhibited by the heavy metals mercury, silver and chromium. Biochemical analysis identified the bacterium as Pseudomonas putida strain Amr-12. Phenol and phenolics cannot support molybdenum reduction. However, the bacterium was able to grow on the phenolic compounds (phenol and catechol with observable lag periods. Maximum growth on phenol and catechol occurred around the concentrations of 600 mg∙L-1. The ability of this bacterium to detoxify molybdenum and grown on toxic phenolic makes this bacterium an important tool for bioremediation.

Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer, in Danish postmenopausal women

DEFF Research Database (Denmark)

Egeberg, Rikke; Olsen, Anja; Autrup, Herman

2008-01-01

The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study...... (1993-2000). Three hundred and seventy-eight breast cancer cases were identified and matched to 378 controls. The incidence rate ratio (95% confidence interval) for breast cancer was 1.09 (1.02-1.17) for total meat, 1.15 (1.01-1.31) for red meat and 1.23 (1.04-1.45) for processed meat per 25 g daily...... total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (P-interaction=0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has...

Acinetobacter baumannii K13 and K73 capsular polysaccharides differ only in K-unit side branches of novel non-2-ulosonic acids: di-N-acetylated forms of either acinetaminic acid or 8-epiacinetaminic acid.

Science.gov (United States)

Kenyon, Johanna J; Kasimova, Anastasiya A; Notaro, Anna; Arbatsky, Nikolay P; Speciale, Immacolata; Shashkov, Alexander S; De Castro, Cristina; Hall, Ruth M; Knirel, Yuriy A

2017-11-27

Structures of capsular polysaccharides of Acinetobacter baumannii isolates carrying KL13 and KL73 gene clusters were established. The closely related KL73 and KL13 gene clusters differ only by one gene in the module responsible for synthesis of the non-2-ulosonic acids. The K13 and K73 polysaccharides differ only in a single side-chain sugar, which is either 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-altro- or -d-glycero-l-altro-non-2-ulosonic acid [di-N-acetylated forms of acinetaminic acid (Aci5Ac7Ac) or 8-epiacinetaminic acid (8eAci5Ac7Ac), respectively]. The KL13 also is closely related to the KL12 gene cluster, which contains a different wzy gene encoding the K unit polymerase. Accordingly, the otherwise near identical K units are linked differently via an α-d-FucpNAc-(1 → 4)-d-Galp linkage in K13 and K73 or an α-d-FucpNAc-(1 → 3)-d-GalpNAc linkage in K12. This finding confirms the predicted substrate of the ItrB3 initiating transferase as d-FucpNAc. Glycosyltransferases predicted to catalyse the linkage of d-Galp or d-GalpNAc to l-FucpNAc in the growing K13 and K73 or K12 units, respectively, differ by only two amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationships between acute toxicities of para nitrophenol (p-NP) and nitrobenzene (NB) to Daphnia magna and Photobacterium phosphoreum: Physicochemical properties and metabolites under anaerobic/aerobic sequentials

Energy Technology Data Exchange (ETDEWEB)

Sponza, Delia Teresa, E-mail: delya.sponza@deu.edu.tr [Dokuz Eyluel University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, Buca, Izmir (Turkey); Kuscu, Ozlem Selcuk [Department of Environmental Engineering, Engineering and Architecture Faculty, Sueleyman Demirel University, Cuenuer Campus, 32260 Isparta (Turkey)

2011-01-30

In this study, the acute toxicities of nitrobenzene (NB) and para nitrophenol (p-NP) were investigated in a high rate sequential anaerobic migrating blanket (AMBR)/aerobic completely stirred tank reactor (CSTR) using Microtox and Daphnia magna tests. After sequential anaerobic and aerobic treatments, the inhibitions in the Microtox bacteria decreased from an initial 78.10-48.20% and 4.00%, respectively, in wastewater containing 40.00 mg/L p-NP. The inhibitions of the influent wastewater containing 60.00 mg/L NB decreased from 72.10% to 45.30% and to 4.00% after anaerobic and aerobic treatment, respectively. The acute toxicity removals were 94% and 93% in the effluent of the whole sequential system, for p-NP and NB, respectively. The acute toxicity in the influent was dependent on the parent NB and p-NP concentrations and ons their physicochemical properties such as hydrophobicity, octanol/water partition coefficient and vapour density for both Microtox bacteria and Daphnia magna while the toxicity in the effluent of the anaerobic reactor was strongly dependent on the metabolites of p-NP (p-amino phenol, phenol, NH{sub 4}-N) and NB (aniline) for Microtox test. This effluent was not toxic to Daphnia magna.

Crystal Structure of TDP-Fucosamine Acetyl Transferase (WECD) from Escherichia Coli, an Enzyme Required for Enterobacterial Common Antigen Synthesis

International Nuclear Information System (INIS)

Hung, M.; Rangarajan, E.; Munger, C.; Nadeau, G.; Sulea, T.; Matte, A.

2006-01-01

Enterobacterial common antigen (ECA) is a polysaccharide found on the outer membrane of virtually all gram-negative enteric bacteria and consists of three sugars, N-acetyl-D-glucosamine, N-acetyl-D-mannosaminuronic acid, and 4-acetamido-4,6-dideoxy-D-galactose, organized into trisaccharide repeating units having the sequence →(3)-α-D-Fuc4NAc-(1→4)-β-D-ManNAcA-(1→4)-α-D-GlcNAc-(1→). While the precise function of ECA is unknown, it has been linked to the resistance of Shiga-toxin-producing Escherichia coli (STEC) O157:H7 to organic acids and the resistance of Salmonella enterica to bile salts. The final step in the synthesis of 4-acetamido-4,6-dideoxy-D-galactose, the acetyl-coenzyme A (CoA)-dependent acetylation of the 4-amino group, is carried out by TDP-fucosamine acetyltransferase (WecD). We have determined the crystal structure of WecD in apo form at a 1.95-Angstroms resolution and bound to acetyl-CoA at a 1.66-Angstroms resolution. WecD is a dimeric enzyme, with each monomer adopting the GNAT N-acetyltransferase fold, common to a number of enzymes involved in acetylation of histones, aminoglycoside antibiotics, serotonin, and sugars. The crystal structure of WecD, however, represents the first structure of a GNAT family member that acts on nucleotide sugars. Based on this cocrystal structure, we have used flexible docking to generate a WecD-bound model of the acetyl-CoA-TDP-fucosamine tetrahedral intermediate, representing the structure during acetyl transfer. Our structural data show that WecD does not possess a residue that directly functions as a catalytic base, although Tyr208 is well positioned to function as a general acid by protonating the thiolate anion of coenzyme A.

N,N-dichloro-4-methylbenzenesulphonimide as a novel and efficient catalyst for acetylation of alcohols under mild conditions

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Khazaei Ardeshir

2006-01-01

Full Text Available Structurally diverse alcohols were acetylated in a clean and efficient reaction with acetic anhydride based on the use of a catalytic amount of N,N-dichloro-4-methylbenzenesulphonimide in dichloromethane. All reactions were performed at room temperature in good to excellent yields.

Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

Science.gov (United States)

Dwyer, Jessica B; Janssen, Jennifer; Luckasevic, Todd M; Williams, Karl E

2018-01-01

Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. © 2017 American Academy of Forensic Sciences.

Investigation of free amino acid, total phenolics, antioxidant activity and purine alkaloids to assess the health properties of non-Camellia tea

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Wu Bi

2016-03-01

Full Text Available To find novel functional beverages from folk teas, 33 species of frequently used non-Camellia tea (plants other than Camellia were collected and compared with Camellia tea (green tea, pu-erh tea and black tea for the first time. Data are reported here on the quantities of 20 free amino acids (FAAs and three purine alkaloids (measured by UHPLC, total polyphenols (measured by Folin-Ciocalteu assay, and antioxidant activity (DPPH. The total amounts of FAAs in non-Camellia tea (0.62–18.99 mg/g are generally less than that of Camellia tea (16.55–24.99 mg/g. However, for certain FAAs, the quantities were much higher in some non-Camellia teas, such as γ-aminobutyric acid in teas from Ampelopsis grossedentata, Isodon serra and Hibiscus sabdariffa. Interestingly, theanine was detected in tea from Potentilla fruticosa (1.16±0.81 mg/g. Furthermore, the content of polyphenols in teas from A. grossedentata, Acer tataricum subsp. ginnala are significantly higher than those from Camellia tea; teas from I. serra, Pistacia chinensis and A. tataricum subsp. ginnala have remarkable antioxidant activities similar to the activities from green tea (44.23 μg/mL. Purine alkaloids (caffeine, theobromine and theophylline were not detected in non-Camellia teas. The investigation suggest some non-Camellia teas may be great functional natural products with potential for prevention of chronic diseases and aging, by providing with abundant polyphenols, antioxidants and specific FAAs.

Investigation of free amino acid, total phenolics, antioxidant activity and purine alkaloids to assess the health properties of non-Camellia tea.

Science.gov (United States)

Bi, Wu; He, Chunnian; Ma, Yunyun; Shen, Jie; Zhang, Linghua Harris; Peng, Yong; Xiao, Peigen

2016-03-01

To find novel functional beverages from folk teas, 33 species of frequently used non-Camellia tea (plants other than Camellia) were collected and compared with Camellia tea (green tea, pu-erh tea and black tea) for the first time. Data are reported here on the quantities of 20 free amino acids (FAAs) and three purine alkaloids (measured by UHPLC), total polyphenols (measured by Folin-Ciocalteu assay), and antioxidant activity (DPPH). The total amounts of FAAs in non-Camellia tea (0.62-18.99 mg/g) are generally less than that of Camellia tea (16.55-24.99 mg/g). However, for certain FAAs, the quantities were much higher in some non-Camellia teas, such as γ-aminobutyric acid in teas from Ampelopsis grossedentata, Isodon serra and Hibiscus sabdariffa. Interestingly, theanine was detected in tea from Potentilla fruticosa (1.16±0.81 mg/g). Furthermore, the content of polyphenols in teas from A. grossedentata, Acer tataricum subsp. ginnala are significantly higher than those from Camellia tea; teas from I. serra, Pistacia chinensis and A. tataricum subsp. ginnala have remarkable antioxidant activities similar to the activities from green tea (44.23 μg/mL). Purine alkaloids (caffeine, theobromine and theophylline) were not detected in non-Camellia teas. The investigation suggest some non-Camellia teas may be great functional natural products with potential for prevention of chronic diseases and aging, by providing with abundant polyphenols, antioxidants and specific FAAs.

Hydrogen/deuterium exchange of cross-linkable alpha-amino acid derivatives in deuterated triflic acid

OpenAIRE

Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Masuda, Katsuyoshi; Sakihama, Yasuko; Hashidoko, Yasuyuki; Hatanaka, Yasumaru; Hashimoto, Makoto

2014-01-01

In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable alpha-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetyl-protected natural aromatic alpha-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotect...

Structural studies on a non-toxic homologue of type II RIPs from ...

Indian Academy of Sciences (India)

Structural studies on a non-toxic homologue of type II RIPs from bitter gourd: Molecular basis of non-toxicity, conformational selection and glycan structure. MS accepted http://www.ias.ac.in/jbiosci. THYAGESHWAR CHANDRAN, ALOK SHARMA and M VIJAYAN. J. Biosci. 40(5), October 2015, 929–941, © Indian Academy of ...

Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism*

Science.gov (United States)

Dyachok, Julia; Earnest, Svetlana; Iturraran, Erica N.; Cobb, Melanie H.

2016-01-01

The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cell growth with its nutritional, hormonal, energy, and stress status. Amino acids are critical regulators of mTORC1 that permit other inputs to mTORC1 activity. However, the roles of individual amino acids and their interactions in mTORC1 activation are not well understood. Here we demonstrate that activation of mTORC1 by amino acids includes two discrete and separable steps: priming and activation. Sensitizing mTORC1 activation by priming amino acids is a prerequisite for subsequent stimulation of mTORC1 by activating amino acids. Priming is achieved by a group of amino acids that includes l-asparagine, l-glutamine, l-threonine, l-arginine, l-glycine, l-proline, l-serine, l-alanine, and l-glutamic acid. The group of activating amino acids is dominated by l-leucine but also includes l-methionine, l-isoleucine, and l-valine. l-Cysteine predominantly inhibits priming but not the activating step. Priming and activating steps differ in their requirements for amino acid concentration and duration of treatment. Priming and activating amino acids use mechanisms that are distinct both from each other and from growth factor signaling. Neither step requires intact tuberous sclerosis complex of proteins to activate mTORC1. Concerted action of priming and activating amino acids is required to localize mTORC1 to lysosomes and achieve its activation. PMID:27587390

Investigations into the influence of airborne pollutants on the metabolism of secondary phenolic substances and amino acids. Untersuchungen ueber den Einfluss von Luftschadstoffen auf den Stoffwechsel von phenolischen Sekundaerstoffen und Aminosaeuren

Energy Technology Data Exchange (ETDEWEB)

Strack, D.

1988-10-01

Quantitative analyses of secondary phenols, free amino acids, and of the enzyme activities arginase and asparaginase were carried out on spruce needles from six different forest sites in North-Rhine Westphalia. In addition, the effects of ozone on spruce aged seven to eight years were investigated. The aim of this was to find out whether there is a correlation between the phenol and amino acid metabolism and the damage rate in older spruce (31 to 60 years) and in younger spruce exposed to ozone. No correlation could be established with a single exception: In one site, the free amino acid pattern showed a 10-fold increase of arginine and an accumulation of ornithine and lysine. This indicates a disturbed nitrogen metabolism, in particular a stimulation of the urea cycle, which may be caused by anthropogenic over fertilizing with nitrogen. The findings for the spruce exposed to ozone indicate a more complex effect on the needle metabolism, which affects both the phenol metabolism (strong decrease of the catechine concentration) and the amino acid metabolism (increase of the alanine concentration). This may be caused by damaged membranes (i.e. higher permeability accompanied by sensitive changes in the metabolic compartmenting) or by a potential increase of transaminase activities. (orig./MG).

Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

Directory of Open Access Journals (Sweden)

Nádia Rezende Barbosa Raposo

2012-10-01

Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

Directory of Open Access Journals (Sweden)

Micovic Zarko

2016-09-01

Full Text Available Hyperhomocysteinemia (HHC, both basal and after methionine load, may occur due to genetic disorders or deficiencies of nutrients that affect the remethylation or trans-sulphuration pathways during methionine metabolism. HHC is involved in the pathogenesis of many illnesses as a result of its prooxidative effect and its impairment of antioxidative protection. The aim was to examine the effects of subchronic methionine overload on the body weight and standard biochemical parameters in rat serum and to examine whether simultaneous subchronic intraperotoneal administration of methionine alone or together with L-cysteine or N-acetyl-cysteine resulted in a change in the body weight and biochemical parameters in the rat serum. The research was conducted during a three-week period (male Wistar albino rats, n=36, body weight of approximately 160 g, age of 15-20 days, and the animals were divided into a control group and three experimental groups of 8-10 animals each: a control group (0.9% sodium chloride 0.1-0.2 ml/day; b methionine (0.8 mmol/kg/bw/day (MET group; c methionine (0.8 mmol/kg/bw/day + L-cysteine (7 mg/kg/bw/day (L-cys+MET group; and d methionine (0.8 mmol/kg/bw/day + N-acetyl-L-cysteine (50 mg/kg/bw/day (NAC+MET group. In addition to the body weight monitoring, the levels of total homocysteine and the standard biochemical parameters in blood samples (plasma or serum were determined. The results indicated that monitoring the homocysteine levels and standard biochemical parameters in blood could be used for analysis and could provide an excellent guideline for distinguishing between toxic and non-toxic doses of methionine intake, which may be meaningful for clinical applications.

A Better Understanding of Protein Structure and Function by the Synthesis and Incorporation of Selenium- and Tellurium Containing Tryptophan Analogs

Energy Technology Data Exchange (ETDEWEB)

Helmey, Sherif Samir [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Rice, Ambrose Eugene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Hatch, Duane Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Silks, Louis A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Marti-Arbona, Ricardo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division

2016-08-17

Unnatural heavy metal-containing amino acid analogs have shown to be very important in the analysis of protein structure, using methods such as X-ray crystallography, mass spectroscopy, and NMR spectroscopy. Synthesis and incorporation of selenium-containing methionine analogs has already been shown in the literature however with some drawbacks due to toxicity to host organisms. Thus synthesis of heavy metal tryptophan analogs should prove to be more effective since the amino acid tryptophan is naturally less abundant in many proteins. For example, bioincorporation of β-seleno[3,2-b]pyrrolyl-L-alanine ([4,5]SeTrp) and β-selenolo[2,3-b]pyrrolyl-L-alanine ([6,7]SeTrp) has been shown in the following proteins without structural or catalytic perturbations: human annexin V, barstar, and dihydrofolate reductase. The reported synthesis of these Se-containing analogs is currently not efficient for commercial purposes. Thus a more efficient, concise, high-yield synthesis of selenotryptophan, as well as the corresponding, tellurotryptophan, will be necessary for wide spread use of these unnatural amino acid analogs. This research will highlight our progress towards a synthetic route of both [6,7]SeTrp and [6,7]TeTrp, which ultimately will be used to study the effect on the catalytic activity of Lignin Peroxidase (LiP).

Investigation of Phenol Removal from Aqueous Solutions by Electrofenton and Electropersulfate Processes

Directory of Open Access Journals (Sweden)

Alireza Rahmani

2016-11-01

Full Text Available Phenol, or benzene hydroxyl is a toxic aromatic hydrocarbon discharged into the environment through certian industrial effluents which, thereby, pollute water resources. This study examines phenol removal from aqueous solutions through electro-Fenton and electro/persulfate processes using iron electrodes. For this purpose, a laboratory-scale electrochemical batch reactor was used that was equipped with four electrodes and a direct DC power supply. In the tests carried out, the effects of operational parameters such as initial pH; current density; and initial concentrations of phenol, hydrogen peroxide, and persulfate on the removal of phenol were investigated. The results showed that EPS and EF processes achieved phenol removal efficiencies of 95.18% and 93.99%, respectively, at operating conditions of pH = 3, initial phenol concentration of 100 mg/l, hydrogen peroxide and persulfate concentration of 0. 4 mM, and a current density 0.07A/dm2 over 45 min. Increasing persulfate and hydrogen peroxide concentration from 0.4 to 0.8 mM reduced phenol removal efficiencies from 95.18% and 93.99% to 43% and 85%, respectively. Generally speaking, EPS and EF processes exhibited almost identical phenol removal efficiencies. Finally, the integrated electrochemical and persulphate process was found to be more productive in producing electrical iron and persulphate activation than using each single process in isolation.

Sorption of a phenols mixture in aqueous solution with activated carbon

International Nuclear Information System (INIS)

Mejia M, D.

2004-01-01

The constant population growth and the quick industrialization have caused severe damages to our natural aquifer resources for a great variety of organic and inorganic pollutants. Among these they are those phenol compounds that are highly toxic, resistant (to the degradation chemistry) and poorly biodegradable. The phenolic compounds is used in a great variety of industries, like it is the production of resins, nylon, plastifiers, anti-oxidants, oil additives, drugs, pesticides, colorants, explosives, disinfectants and others. The disseminated discharges or effluents coming from the industrial processes toward lakes and rivers are causing a growing adverse effect in the environment, as well as a risk for the health. Numerous studies exist on the phenols removal and phenols substituted for very varied techniques, among them they are the adsorption in activated carbon. This finishes it has been used successfully for the treatment of residual waters municipal and industrial and of drinking waters and it is considered as the best technique available to eliminate organic compounds not biodegradable and toxic present in aqueous solution (US EPA, 1991). However a little information exists on studies carried out in aqueous systems with more of a phenolic compound. The activated carbon is broadly used as adsorbent due to its superficial properties in the so much treatment of water as of aqueous wastes, adsorbent for the removal of organic pollutants. The main objective of this work is the adsorption of a aqueous mixture of phenol-4 chloro phenol of different concentrations in activated carbon of mineral origin of different meshes and to diminish with it their presence in water. The experiments were carried out for lots, in normal conditions of temperature and pressure. The experimental results show that the removal capacity depends so much of the superficial properties of the sorbent like of the physical properties and chemical of the sorbate. The isotherms were carried

DEUTERIUM FRACTIONATION DURING AMINO ACID FORMATION BY PHOTOLYSIS OF INTERSTELLAR ICE ANALOGS CONTAINING DEUTERATED METHANOL

Energy Technology Data Exchange (ETDEWEB)

Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira [Institute of Low Temperature Science, Hokkaido University, N19W8, Kita-ku, Sapporo, Hokkaido 060-0819 (Japan); Takano, Yoshinori, E-mail: oba@lowtem.hokudai.ac.jp [Department of Biogeochemistry, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), 2-15 Natsushima, Yokosuka, Kanagawa 237-0061 (Japan)

2016-08-10

Deuterium (D) atoms in interstellar deuterated methanol might be distributed into complex organic molecules through molecular evolution by photochemical reactions in interstellar grains. In this study, we use a state-of-the-art high-resolution mass spectrometer coupled with a high-performance liquid chromatography system to quantitatively analyze amino acids and their deuterated isotopologues formed by the photolysis of interstellar ice analogs containing singly deuterated methanol CH{sub 2}DOH at 10 K. Five amino acids (glycine, α -alanine, β -alanine, sarcosine, and serine) and their deuterated isotopologues whose D atoms are bound to carbon atoms are detected in organic residues formed by photolysis followed by warming up to room temperature. The abundances of singly deuterated amino acids are in the range of 0.3–1.1 relative to each nondeuterated counterpart, and the relative abundances of doubly and triply deuterated species decrease with an increasing number of D atoms in a molecule. The abundances of amino acids increase by a factor of more than five upon the hydrolysis of the organic residues, leading to decreases in the relative abundances of deuterated species for α -alanine and β -alanine. On the other hand, the relative abundances of the deuterated isotopologues of the other three amino acids did not decrease upon hydrolysis, indicating different formation mechanisms of these two groups upon hydrolysis. The present study facilitates both qualitative and quantitative evaluations of D fractionation during molecular evolution in the interstellar medium.

DEUTERIUM FRACTIONATION DURING AMINO ACID FORMATION BY PHOTOLYSIS OF INTERSTELLAR ICE ANALOGS CONTAINING DEUTERATED METHANOL

International Nuclear Information System (INIS)

Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira; Takano, Yoshinori

2016-01-01

Deuterium (D) atoms in interstellar deuterated methanol might be distributed into complex organic molecules through molecular evolution by photochemical reactions in interstellar grains. In this study, we use a state-of-the-art high-resolution mass spectrometer coupled with a high-performance liquid chromatography system to quantitatively analyze amino acids and their deuterated isotopologues formed by the photolysis of interstellar ice analogs containing singly deuterated methanol CH 2 DOH at 10 K. Five amino acids (glycine, α -alanine, β -alanine, sarcosine, and serine) and their deuterated isotopologues whose D atoms are bound to carbon atoms are detected in organic residues formed by photolysis followed by warming up to room temperature. The abundances of singly deuterated amino acids are in the range of 0.3–1.1 relative to each nondeuterated counterpart, and the relative abundances of doubly and triply deuterated species decrease with an increasing number of D atoms in a molecule. The abundances of amino acids increase by a factor of more than five upon the hydrolysis of the organic residues, leading to decreases in the relative abundances of deuterated species for α -alanine and β -alanine. On the other hand, the relative abundances of the deuterated isotopologues of the other three amino acids did not decrease upon hydrolysis, indicating different formation mechanisms of these two groups upon hydrolysis. The present study facilitates both qualitative and quantitative evaluations of D fractionation during molecular evolution in the interstellar medium.

Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, a Review of Effectiveness in Reducing HIV Progression

Science.gov (United States)

Hummelen, Ruben; Hemsworth, Jaimie; Reid, Gregor

2010-01-01

Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use. PMID:22254046

Kinetic Effects Of Increased Proton Transfer Distance On Proton-Coupled Oxidations Of Phenol-Amines

Science.gov (United States)

Rhile, Ian J.

2011-01-01

To test the effect of varying the proton donor-acceptor distance in proton-coupled electron transfer (PCET) reactions, the oxidation of a bicyclic amino-indanol (2) is compared with that of a closely related phenol with an ortho CPh2NH2 substituent (1). Spectroscopic, structural, thermochemical and computational studies show that the two amino-phenols are very similar, except that the O⋯N distance (dON) is >0.1 Å longer in 2 than in 1. The difference in dON is 0.13 ± 0.03 Å from X-ray crystallography and 0.165 Å from DFT calculations. Oxidations of these phenols by outer-sphere oxidants yield distonic radical cations •OAr–NH3+ by concerted proton-electron transfer (CPET). Simple tunneling and classical kinetic models both predict that the longer donor-acceptor distance in 2 should lead to slower reactions, by ca. two orders of magnitude, as well as larger H/D kinetic isotope effects (KIEs). However, kinetic studies show that the compound with the longer proton-transfer distance, 2, exhibits smaller KIEs and has rate constants that are quite close to those of 1. For example, the oxidation of 2 by the triarylamminium radical cation N(C6H4OMe)3•+ (3a+) occurs at (1.4 ± 0.1) × 104 M-1 s-1, only a factor of two slower than the closely related reaction of 1 with N(C6H4OMe)2(C6H4Br)•+ (3b+). This difference in rate constants is well accounted for by the slightly different free energies of reaction: ΔG°(2 + 3a+) = +0.078 V vs. ΔG°(1 + 3b+) = +0.04 V. The two phenol-amines do display some subtle kinetic differences: for instance, compound 2 has a shallower dependence of CPET rate constants on driving force (Brønsted α, Δln(k)/Δln(Keq)). These results show that the simple tunneling model is not a good predictor of the effect of proton donor-acceptor distance on concerted-electron transfer reactions involving strongly hydrogen-bonded systems. Computational analysis of the observed similarity of the two phenols emphasizes the importance of the highly

Involvement of tyrosine residues, N-terminal amino acids, and beta-alanine in insect cuticular sclerotization.

Science.gov (United States)

Andersen, Svend Olav

2007-09-01

During sclerotization of insect cuticle the acyldopamines, N-acetyldopamine (NADA) and N-beta-alanyldopamine (NBAD), are oxidatively incorporated into the cuticular matrix, thereby hardening and stabilizing the material by forming crosslinks between the proteins in the cuticular matrix and by forming polymers filling the intermolecular spaces in the cuticle. Sclerotized cuticle from the locust, Schistocerca gregaria, and the beetle, Tenebrio molitor, was hydrolyzed in dilute hydrochloric acid, and from the hydrolysates some components presumably degradation products of cuticular crosslinks were isolated. In two of the components, the sidechain of 3,4-dihydroxyacetophenone was linked to the amino groups of glycine and beta-alanine, respectively, and in the third component to the phenolic group of tyrosine. These three compounds, glycino-dihydroxyacetophenone, beta-alanino-dihydroxyacetophenone, and O-tyrosino-dihydroxyacetophenone, as well as the previously reported compound, lysino-dihydroxyacetophenone [Andersen, S.O., Roepstorff, P., 2007. Aspects of cuticular sclerotization in the locust, Schistocerca gregaria, and the beetle, Tenebrio molitor. Insect Biochem. Mol. Biol. 37, 223-234], are suggested to be degradation products of cuticular crosslinks, in which amino acid residues formed linkages to both the alpha- and beta-positions of the sidechain of acyldopamines.

Trichoderma reesei CE16 acetyl esterase and its role in enzymatic degradation of acetylated hemicellulose

DEFF Research Database (Denmark)

Biely, Peter; Cziszarava, Maria; Agger, Jane W.

2014-01-01

Results The combined action of GH10 xylanase and acetylxylan esterases (AcXEs) leads to formation of neutral and acidic xylooligosaccharides with a few resistant acetyl groups mainly at their non-reducing ends. We show here that these acetyl groups serve as targets for TrCE16 AcE. The most promin...

Correlation of Global N-Acetyl Aspartate With Cognitive Impairment in Multiple Sclerosis

DEFF Research Database (Denmark)

Kahr Mathiesen, Henrik; Jonsson, Agnete; Tscherning, Thomas

2006-01-01

BACKGROUND: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging. OBJECTIVE: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis...

Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

Science.gov (United States)

Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

2012-08-01

Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microstructure and properties of nitrogen ion implantation/AlN/CrAlN/MoS{sub 2}-phenolic resin duplex coatings on magnesium alloys

Energy Technology Data Exchange (ETDEWEB)

Xie, Zhiwen [University of Science and Technology Liaoning, Anshan 114051 (China); Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714 (China); Chen, Qiang, E-mail: 2009chenqiang@163.com [Southwest Technique and Engineering Research Institute, Chongqing 400039 (China); Chen, Tian [Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714 (China); Gao, Xu; Yu, Xiaoguang; Song, Hua; Feng, Yongjun [University of Science and Technology Liaoning, Anshan 114051 (China)

2015-06-15

The novel nitrogen ion implantation/AlN/CrAlN/MoS{sub 2}-phenolic resin duplex coatings are fabricated on the AM60 magnesium alloys. The microstructure, tribological and electrochemical properties of the duplex coatings are characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, nano-indenter, electrochemical corrosion and wear tester. These studies reveal that the MoS{sub 2}-phenolic resin coating has a two-phase microstructure crystalline MoS{sub 2} particles embedded in the amorphous phenolic resin matrix. The single-layer MoS{sub 2}-phenolic resin enhances the corrosion resistance of magnesium alloys, but shows poor wear resistance due to the low substrate's load bearing capacity. The addition of nitrogen ion implantation/AlN/CrAlN interlayer in the MoS{sub 2}-phenolic resin/substrate system greatly enhances the substrate's load bearing capacity. The AlN/CrAlN/MoS{sub 2}-phenolic resin duplex coating with a high load bearing capacity demonstrates super wear resistance (i.e., long wear life and low friction coefficient). In addition, the nitrogen ion implantation/AlN interlayer greatly depresses the effect of galvanic corrosion because its potential is close to that of the magnesium alloys, but the nitrogen ion implantation/AlN/CrAlN interlayer is inefficient in reducing the galvanic corrosion due to the large potential difference between the CrN phase and the substrate. As a result, the nitrogen ion implantation/AlN/MoS{sub 2}-phenolic resin duplex coating shows a better corrosion resistance compared to the nitrogen ion implantation/AlN/CrAlN/MoS{sub 2}-phenolic resin. - Highlights: • Ion implantation/AlN/CrAlN/MoS{sub 2}-phenolic resin duplex coatings were presented. • Ion implantation/AlN/CrAlN interlayer greatly enhanced the load bearing capacity. • Ion implantation/AlN interlayer greatly depressed the effect of galvanic corrosion. • The

Relationships between chemical oxygen demand (COD) components and toxicity in a sequential anaerobic baffled reactor/aerobic completely stirred reactor system treating Kemicetine

Energy Technology Data Exchange (ETDEWEB)

Sponza, Delia Teresa, E-mail: delya.sponza@deu.edu.tr [Department of Environmental Engineering, Faculty of Engineering, Dokuz Eyluel University, Buca Kaynaklar Campus, Tinaztepe, 35160 Izmir (Turkey); Demirden, Pinar, E-mail: pinar.demirden@kozagold.com [Environmental Engineer, Koza Gold Company, Environmental Department, Ovacik, Bergama Izmir (Turkey)

2010-04-15

In this study the interactions between toxicity removals and Kemicetine, COD removals, intermediate products of Kemicetine and COD components (CODs originating from slowly degradable organics, readily degradable organics, inert microbial products and from the inert compounds) were investigated in a sequential anaerobic baffled reactor (ABR)/aerobic completely stirred tank reactor (CSTR) system with a real pharmaceutical wastewater. The total COD and Kemicetine removal efficiencies were 98% and 100%, respectively, in the sequential ABR/CSTR systems. 2-Amino-1 (p-nitrophenil)-1,3 propanediol, l-p-amino phenyl, p-amino phenol and phenol were detected in the ABR as the main readily degradable inter-metabolites. In the anaerobic ABR reactor, the Kemicetin was converted to corresponding inter-metabolites and a substantial part of the COD was removed. In the aerobic CSTR reactor the inter-metabolites produced in the anaerobic reactor were completely removed and the COD remaining from the anerobic reactor was biodegraded. It was found that the COD originating from the readily degradable organics did not limit the anaerobic degradation process, while the CODs originating from the slowly degradable organics and from the inert microbial products significantly decreased the anaerobic ABR reactor performance. The acute toxicity test results indicated that the toxicity decreased from the influent to the effluent of the aerobic CSTR reactor. The ANOVA test statistics showed that there was a strong linear correlation between acute toxicity, CODs originating from the slowly degradable organics and inert microbial products. A weak correlation between acute toxicity and CODs originating from the inert compounds was detected.

Relationships between chemical oxygen demand (COD) components and toxicity in a sequential anaerobic baffled reactor/aerobic completely stirred reactor system treating Kemicetine

International Nuclear Information System (INIS)

Sponza, Delia Teresa; Demirden, Pinar

2010-01-01

In this study the interactions between toxicity removals and Kemicetine, COD removals, intermediate products of Kemicetine and COD components (CODs originating from slowly degradable organics, readily degradable organics, inert microbial products and from the inert compounds) were investigated in a sequential anaerobic baffled reactor (ABR)/aerobic completely stirred tank reactor (CSTR) system with a real pharmaceutical wastewater. The total COD and Kemicetine removal efficiencies were 98% and 100%, respectively, in the sequential ABR/CSTR systems. 2-Amino-1 (p-nitrophenil)-1,3 propanediol, l-p-amino phenyl, p-amino phenol and phenol were detected in the ABR as the main readily degradable inter-metabolites. In the anaerobic ABR reactor, the Kemicetin was converted to corresponding inter-metabolites and a substantial part of the COD was removed. In the aerobic CSTR reactor the inter-metabolites produced in the anaerobic reactor were completely removed and the COD remaining from the anerobic reactor was biodegraded. It was found that the COD originating from the readily degradable organics did not limit the anaerobic degradation process, while the CODs originating from the slowly degradable organics and from the inert microbial products significantly decreased the anaerobic ABR reactor performance. The acute toxicity test results indicated that the toxicity decreased from the influent to the effluent of the aerobic CSTR reactor. The ANOVA test statistics showed that there was a strong linear correlation between acute toxicity, CODs originating from the slowly degradable organics and inert microbial products. A weak correlation between acute toxicity and CODs originating from the inert compounds was detected.

Computational Study of Environmental Effects on Torsional Free Energy Surface of N-Acetyl-N'-methyl-L-alanylamide Dipeptide

Science.gov (United States)

Carlotto, Silvia; Zerbetto, Mirco

2014-01-01

We propose an articulated computational experiment in which both quantum mechanics (QM) and molecular mechanics (MM) methods are employed to investigate environment effects on the free energy surface for the backbone dihedral angles rotation of the small dipeptide N-Acetyl-N'-methyl-L-alanylamide. This computation exercise is appropriate for an…

Inhibition of Urease Enzyme Production and some Other Virulence Factors Expression in Proteus mirabilis by N-Acetyl Cysteine and Dipropyl Disulphide.

Science.gov (United States)

Abdel-Baky, Rehab Mahmoud; Ali, Mohamed Abdullah; Abuo-Rahma, Gamal El-Din Ali A; AbdelAziz, Neveen

2017-01-01

Proteus mirabilis is one of the important pathogens that colonize the urinary tract and catheters resulting in various complications, such as blockage of the catheters and the formation of infective stones. In this study we evaluated the effect of N-acetyl cysteine (NAC) and dipropyl disulphide on some virulence factors expressed by a Proteus mirabilis strain isolated from a catheterized patient. Antibacterial activity of both compounds was determined by broth microdilution method. Their effect on different types of motility was determined by LB medium with variable agar content and sub-MIC of each drug. Their effect on adherence and mature biofilms was tested by tissue culture plate assay. Inhibitory effect on urease production was determined and supported by molecular docking studies. The minimum inhibitory concentration (MIC) of NAC and dipropyl disulphide was 25 mM and 100 mM, respectively. Both compounds decreased the swarming ability and biofilm formation of the tested isolate in a dose-dependent manner. NAC had higher urease inhibitory activity (IC50 249 ±0.05 mM) than that shown by dipropyl disulphide (IC 50 10±0.2 mM). Results were supported by molecular docking studies which showed that NAC and dipropyl disulphide interacted with urease enzyme with binding free energy of -4.8 and -8.528 kcal/mol, respectively. Docking studies showed that both compounds interacted with Ni ion and several amino acids (His-138, Gly-279, Cysteine-321, Met-366 and His-322) which are essential for the enzyme activity. NAC and dipropyl disulphide could be used in the control of P. mirabilis urinary tract infections.

Efeito dos aminoácidos de cadeia ramificada no músculo imobilizado e no músculo desnervado = Effect of branched - chain amino acids on immobilized skeletal muscle and denervated muscle

Directory of Open Access Journals (Sweden)

Pezolato, Vitor Alexandre

2014-01-01

Full Text Available Objetivo: Este trabalho teve como objetivo avaliar histologicamente o músculo sóleo imobilizado e desnervado de ratos suplementados com aminoácidos de cadeia ramificada. Materiais e Métodos: Para a realização da pesquisa foram utilizados 30 ratos navergicus albinus machos, variedade Wistar, com 3 a 4 meses de vida, divididos em 6 grupos (n=5 e denominados: controle (C, desnervado 7 dias (D, imobilizado 7 dias (I, suplementado com aminoácidos de cadeia ramificada 7 dias (BCAA, desnervado suplementado com aminoácidos de cadeia ramificada (D+BCAA e imobilizado suplementado com aminoácidos de cadeia ramificada (I+BCAA. Os animais desnervados passaram pelo seccionamento do nervo ciático (1 cm. O s animais dos grupos imobilizados receberam uma órtese de resina acrílica acoplada na pata posterior promovendo a imobilização. Após a fase experimental os animais foram eutanasiados e os músculos foram analisados histologicamente. O teste de Shapiro - Wilk avaliou a normalidade dos dados, seguido da análise de variância e, posteriormente, Tukey - Kramer com nível de significância menor de 5%. Resultados: A suplementação aumentou a área de secçã o transversa da fibra muscular em 74,94% no grupo I+BCAA e 90,37% no grupo D+BCAA em relação aos grupos I e D, respectivamente. Houve aumento de 97,21% na densidade de área de tecido conjuntivo no grupo BCAA em relação ao grupo C, porém a suplementação pro moveu redução de 34,44% no grupo D+BCAA em relação ao grupo D, no entanto, não houve diferença significativa entre os grupos I+BCAA e I. Conclusão: Observa-se que a utilização dos aminoácidos de cadeia ramificada pode diminuir a atrofia provocada pelo desuso muscular, tanto na condição de desnervação quanto na condição de imobilização

Acetylation of woody lignocellulose: significance and regulation

Directory of Open Access Journals (Sweden)

Prashant Mohan-Anupama Pawar

2013-05-01

Full Text Available Non-cellulosic cell wall polysaccharides constitute approximately one quarter of usable biomass for human exploitation. In contrast to cellulose, these components are usually substituted by O-acetyl groups, which affect their properties and interactions with other polymers, thus affecting their solubility and extractability. However, details of these interactions are still largely obscure. Moreover, polysaccharide hydrolysis to constituent monosaccharides, is hampered by the presence of O-acetyl groups, necessitating either enzymatic (esterase or chemical de-acetylation, increasing the costs and chemical consumption. Reduction of polysaccharide acetyl content in planta is a way to modify lignocellulose towards improved saccharification. In this review we: 1 summarize literature on lignocellulose acetylation in different tree species, 2 present data and current hypotheses concerning the role of O-acetylation in determining woody lignocellulose properties, 3 describe plant proteins involved in lignocellulose O-acetylation, 4 give examples of microbial enzymes capable to de-acetylate lignocellulose, and 5 discuss prospects for exploiting these enzymes in planta to modify xylan acetylation.

Central N-acetyl aspartylglutamate deficit: a possible pathogenesis of schizophrenia.

Science.gov (United States)

Tsai, Shih-Jen

2005-09-01

The "glutamate hypothesis" of schizophrenia has emerged from the finding that phencyclidine (PCP) induces psychotic-like behaviors in rodents, possibly by blocking the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, thereby causing increased glutamate release. N-acetyl aspartylglutamate (NAAG), an endogenous peptide abundant in mammalian nervous systems, is localized in certain brain cells, including cortical and hippocampal pyramidal neurons. NAAG is synthesized from N-acetylaspartate (NAA) and glutamate, and NAA availability may limit the rate of NAAG synthesis. Although NAAG is known to have some neurotransmitter-like functions, NAA does not. NAAG is a highly selective agonist of the type 3 metabotropic glutamate receptor (mGluR3, a presynaptic autoreceptor) and can inhibit glutamate release. In addition, at low levels, NAAG is an NMDA receptor antagonist, and blocking of NMDA receptors may increase glutamate release. Taken together, low central NAAG levels may antagonize the effect of glutamate at NMDA receptors and decrease its agonistic effect on presynaptic mGluR3; both activities could increase glutamate release, similar to the increase demonstrated in the PCP model of schizophrenia. In this report, it is suggested that the central NAAG deficit, possibly through decreased synthesis or increased degradation of NAAG, may play a role in the pathogenesis of schizophrenia. Evidence is presented and discussed from magnetic resonance, postmortem, animal model, schizophrenia treatment, and genetic studies. The central NAAG deficit model of schizophrenia could explain the disease process, from the perspectives of both neurodevelopment and neurodegeneration, and may point to potential treatments for schizophrenia.

N-mercapto acetyl-N'-octyl-O, N″-glycol chitosan as an efficiency oral delivery system of paclitaxel.

Science.gov (United States)

Huo, Meirong; Fu, Ying; Liu, Yanhong; Chen, Qinyu; Mu, Yan; Zhou, Jianping; Li, Lingchao; Xu, Wei; Yin, Tingjie

2018-02-01

Herein, thioglycolic acid modified N-octyl-O, N'-glycol chitosan (N-mercapto acetyl-N'-octyl-O, N″-glycol chitosan, abbreviated as SH-OGC) was synthesized to improve the oral bioavailability of paclitaxel (PTX). PTX was readily solubilized into the hydrophobic inner core of SH-OGC. Pharmacokinetic studies demonstrated that the bioavailability of PTX was greatly enhanced when delivered by SH-OGC compared to Taxol ® or non-sulfhydrylated OGC micelles. Caco-2 cell experiments confirmed PTX or rhodamine-123-loaded SH-OGC demonstrated effective cellular accumulation via caveola-mediated endocytosis along with the inhibition of P-gp efflux. Furthermore, Caco-2 transport studies demonstrated that the mechanistic basis of SH-OGC efficacy was attributed to P-gp inhibition, enhanced permeability of tight junctions and clathrin-mediated transcytosis across the endothelium. In addition, SH-OGC exhibited increased intestinal retention through thiol-mediated mucoadhesion compared with OGC according to results of mucoadhesion evaluation on freshly excised rat intestine. In summary, SH-OGC micelles may present as a promising delivery vehicle for enhancing the oral bioavailability of P-gp substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transport and activation of S-(1,2-dichlorovinyl)-L-cysteine and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine in rat kidney proximal tubules

International Nuclear Information System (INIS)

Zhang, G.H.; Stevens, J.L.

1989-01-01

An important step in understanding the mechanism underlying the tubular specificity of the nephrotoxicity of toxic cysteine conjugates is to identify the rate-limiting steps in their activation. The rate-limiting steps in the activation of toxic cysteine conjugates were characterized using isolated proximal tubules from the rat and 35S-labeled S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAC-DCVC) as model compounds. The accumulation by tubules of 35S radiolabel from both DCVC and NAC-DCVC was time and temperature dependent and was mediated by both Na+-dependent and independent processes. Kinetic studies with DCVC in the presence of sodium revealed the presence of two components with apparent Km and Vmax values of (1) 46 microM and 0.21 nmol/mg min and (2) 2080 microM and 7.3 nmol/mg.min. NAC-DVVC uptake was via a single system with apparent Km and Vmax values of 157 microM and 0.65 nmol/mg.min, respectively. Probenecid, an inhibitor of the renal organic anion transport system, inhibited accumulation of radiolabel from NAC-DCVC, but not from DCVC. The covalent binding of 35S label to cellular macromolecules was much greater from [35S]DCVC than from NAC-[35S]DCVC. Analysis of metabolites showed that a substantial amount of the cellular NAC-[35S]DCVC was unmetabolized while [35S]DCVC was rapidly metabolized to bound 35S-labeled material and unidentified products. The data suggest that DCVC is rapidly metabolized following transport, but that activation of NAC-DCVC depends on a slower rate of deacetylation. The results are discussed with regard to the segment specificity of cysteine conjugate toxicity and the role of disposition in vivo in the nephrotoxicity of glutathione conjugates

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

Science.gov (United States)

Clerici, C; Gentili, G; Boschetti, E; Santucci, C; Aburbeh, A G; Natalini, B; Pellicciari, R; Morelli, A

1994-12-01

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Studies on the Growth Effects of the Canaline-Urea Cycle Amino Acids with Lemna minor L. 1

Science.gov (United States)

Rosenthal, Gerald A.; Gulati, Dushyant K.; Sabharwal, P. S.

1975-01-01

The aquatic microphyte, Lemna minor L., was utilized to assess the relative toxicity and general growth effects of canavanine, canaline, ureidohomoserine (UHS), and canavaninosuccinate (CSA). These amino acids are constituents of the canaline-urea cycle and structural analogues of the ornithine-urea cycle amino acids. Comparative growth studies with L. minor revealed that the canaline-urea cycle amino acids are potent antimetabolites. With the exception of CSA, they are extremely toxic at a concentration of 5 μm. Over a concentration range of 1 to 4 μm, canavanine is the most growth-inhibiting of the canaline-urea cycle amino acids. At or above 5 μm, canavanine and canaline possess comparable toxicity. UHS is less growth-inhibiting than canavanine or canaline, and CSA is the least toxic of the canaline-urea cycle intermediates. PMID:16659316

Effect of phenolic compounds released during degradation of Coir ...

African Journals Online (AJOL)

MICHAEL

www.bioline.org.br/ja. Effect of phenolic compounds released during degradation of Coir pith by ... of the culture filtrate appears to be non toxic in the tested animals @ JASEM. Coir pith is a highly ... degradation of coir pith by fungi and bacteria were already reported, ... no.1 filter paper and used as feed for the experimental ...

Effects of N-acetyl cysteine on lipid levels and on leukocyte and ...

African Journals Online (AJOL)

Introduction: Many of studies have shown that increased lipid levels play a significant role in the pathogenesis of atherosclerosis after splenectomy. We investigated the effects of N-acetyl cysteine (NAC) on lipid parameters and leukocyte and platelet (PLT) levels following splenectomy. Materials and Methods: 32 Sprague.

Fatal Phenol Toxicity Following Attempted Tattoo Removal.

Science.gov (United States)

Li, Zhen; Zhang, Huang; Li, Shu-Hua; Byard, Roger W

2016-07-01

Tattoo removal is increasingly required as the number of, particularly young, people acquiring tattoos is increasing. A 21-year-old man is reported who underwent attempted removal of large dragon tattoo utilizing a tattoo machine that injected a phenol-containing solution. At the end of the 3-h procedure, he collapsed and died. At autopsy, large areas of white skin discoloration with focal necrosis and sloughing were present overlying areas of previous tattooing. Histological examination showed collections of eosinophilic fluid with a minimal chronic inflammatory infiltrate in better preserved areas, with focal areas of dermal necrosis. Toxicology was positive for phenol in cardiac blood and liver tissue. There were no underlying organic disease or injuries present which could have caused or contributed to death. This idiosyncratic method of tattoo removal involving subcutaneous injection of phenol had resulted in death most likely from cardiotoxicity. © 2016 American Academy of Forensic Sciences.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

Science.gov (United States)

Dean, Olivia M; Gray, Kylie M; Villagonzalo, Kristi-Ann; Dodd, Seetal; Mohebbi, Mohammadreza; Vick, Tanya; Tonge, Bruce J; Berk, Michael

2017-03-01

Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

Autoimmune regulator is acetylated by transcription coactivator CBP/p300

Energy Technology Data Exchange (ETDEWEB)

Saare, Mario, E-mail: mario.saare@ut.ee [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); Rebane, Ana [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); SIAF, Swiss Institute of Allergy and Asthma Research, University of Zuerich, Davos (Switzerland); Rajashekar, Balaji; Vilo, Jaak [BIIT, Bioinformatics, Algorithmics and Data Mining group, Institute of Computer Science, University of Tartu, Tartu (Estonia); Peterson, Paert [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia)

2012-08-15

The Autoimmune Regulator (AIRE) is a regulator of transcription in the thymic medulla, where it controls the expression of a large set of peripheral-tissue specific genes. AIRE interacts with the transcriptional coactivator and acetyltransferase CBP and synergistically cooperates with it in transcriptional activation. Here, we aimed to study a possible role of AIRE acetylation in the modulation of its activity. We found that AIRE is acetylated in tissue culture cells and this acetylation is enhanced by overexpression of CBP and the CBP paralog p300. The acetylated lysines were located within nuclear localization signal and SAND domain. AIRE with mutations that mimicked acetylated K243 and K253 in the SAND domain had reduced transactivation activity and accumulated into fewer and larger nuclear bodies, whereas mutations that mimicked the unacetylated lysines were functionally similar to wild-type AIRE. Analogously to CBP, p300 localized to AIRE-containing nuclear bodies, however, the overexpression of p300 did not enhance the transcriptional activation of AIRE-regulated genes. Further studies showed that overexpression of p300 stabilized the AIRE protein. Interestingly, gene expression profiling revealed that AIRE, with mutations mimicking K243/K253 acetylation in SAND, was able to activate gene expression, although the affected genes were different and the activation level was lower from those regulated by wild-type AIRE. Our results suggest that the AIRE acetylation can influence the selection of AIRE activated genes. -- Highlights: Black-Right-Pointing-Pointer AIRE is acetylated by the acetyltransferases p300 and CBP. Black-Right-Pointing-Pointer Acetylation occurs between CARD and SAND domains and within the SAND domain. Black-Right-Pointing-Pointer Acetylation increases the size of AIRE nuclear dots. Black-Right-Pointing-Pointer Acetylation increases AIRE protein stability. Black-Right-Pointing-Pointer AIRE acetylation mimic regulates a different set of AIRE

Identification and genetic characterization of phenol- degrading ...

African Journals Online (AJOL)

SAURABH

2013-02-20

Feb 20, 2013 ... this paper, we reported about the new strain of Acinetobacter sp. ... characteristics of an efficient phenol-degrading microorganism. ... compounds are widespread in the environment. The problem is compounded by the fact that phenol is toxic, ... The phenol biodegradation ability of this bacterium was.

Formation of Amino Acid Precursors by Bombardment of Interstellar Ice Analogs with High Energy Heavy Ions

Science.gov (United States)

Kobayashi, Kensei; Mita, Hajime; Yoshida, Satoshi; Shibata, Hiromi; Enomoto, Shingo; Matsuda, Tomoyuki; Fukuda, Hitoshi; Kondo, Kotaro; Oguri, Yoshiyuki; Kebukawa, Yoko

2016-07-01

A wide variety of organic compounds have been detected in extraterrestrial bodies. It has been recognized that carbonaceous chondrites contain pristine amino acids [1]. There are several scenarios of the formation of such extraterrestrial amino acids or their precursors. Greenberg proposed a scenario that complex organic compounds were formed in interstellar ices in dense clouds, which were brought into solar system small bodies when the solar system was formed [2]. The ice mantles of interstellar dust particles (ISDs) in dense clouds are composed of H2O, CO, CH3OH, CH4, CO2, NH3, etc. In order to verify the scenario, a number of laboratory experiments have been conducted where interstellar ice analogs were irradiated with high-energy particles [3,4] or UV [5,6], and formation of complex organic compounds including amino acid precursors were detected in the products. Though ion-molecular reactions in gaseous phase and surface reactions on the ice mantles have been studied intensively, much less works on cosmic rays-induced reaction have been reported. In order to study possible formation of complex molecules in interstellar ices, frozen mixtures of water, methanol and ammonia with various mixing ratios were irradiated with high-energy heavy ions such as carbon ions (290 MeV/u) and neon ions (400 MeV/u) from HIMAC, NIRS, Japan. For comparison, gaseous mixtures of water, ammonia, carbon monoxide, carbon dioxide, and/or methane were irradiated with protons (2.5 MeV) from a Tandem accelerator, Tokyo Tech, Japan. Amino acids in the products were determined by cation exchange HPLC after acid hydrolysis. Products, both before and after acid hydrolysis, were also characterized by FT-IR and other techniques. Amino acids were detected in the hydrolyzed products after mixture of CH3OH, NH3 and H2O with various mixing ratios were irradiated with heavy ions, including when their mixing ratio was set close to the reported value of the interstellar ices (10:1:37). In the HIMAC

Colorimetric biomimetic sensor systems based on molecularly imprinted polymer membranes for highly-selective detection of phenol in environmental samples

Directory of Open Access Journals (Sweden)

Sergeyeva T. A.

2014-05-01

Full Text Available Aim. Development of an easy-to-use colorimetric sensor system for fast and accurate detection of phenol in envi- ronmental samples. Methods. Technique of molecular imprinting, method of in situ polymerization of molecularly imprinted polymer membranes. Results. The proposed sensor is based on free-standing molecularly imprinted polymer (MIP membranes, synthesized by in situ polymerization, and having in their structure artificial binding sites capable of selective phenol recognition. The quantitative detection of phenol, selectively adsorbed by the MIP membranes, is based on its reaction with 4-aminoantipyrine, which gives a pink-colored product. The intensity of staining of the MIP membrane is proportional to phenol concentration in the analyzed sample. Phenol can be detected within the range 50 nM–10 mM with limit of detection 50 nM, which corresponds to the concentrations that have to be detected in natural and waste waters in accordance with environmental protection standards. Stability of the MIP-membrane-based sensors was assessed during 12 months storage at room temperature. Conclusions. The sensor system provides highly-selective and sensitive detection of phenol in both mo- del and real (drinking, natural, and waste water samples. As compared to traditional methods of phenol detection, the proposed system is characterized by simplicity of operation and can be used in non-laboratory conditions.

Adsorption and release of amino acids mixture onto apatitic calcium phosphates analogous to bone mineral

Science.gov (United States)

El Rhilassi, A.; Mourabet, M.; El Boujaady, H.; Bennani-Ziatni, M.; Hamri, R. El; Taitai, A.

2012-10-01

Study focused on the interaction of adsorbate with poorly crystalline apatitic calcium phosphates analogous to bone mineral. Calcium phosphates prepared in water-ethanol medium at physiological temperature (37 °C) and neutral pH, their Ca/P ratio was between 1.33 and 1.67. Adsorbate used in this paper takes the mixture form of two essential amino acids L-lysine and DL-leucine which have respectively a character hydrophilic and hydrophobic. Adsorption and release are investigated experimentally; they are dependent on the phosphate type and on the nature of adsorbate L-lysine, DL-leucine and their mixture. Adsorption of mixture of amino acids on the apatitic calcium phosphates is influenced by the competition between the two amino acids: L-lysine and DL-leucine which exist in the medium reaction. The adsorption kinetics is very fast while the release kinetics is slow. The chemical composition of apatite has an influence on both adsorption and release. The interactions adsorbate-adsorbent are electrostatic type. Adsorption and release reactions of the amino acid mixture are explained by the existence of the hydrated surface layer of calcium phosphate apatite. The charged sbnd COOsbnd and sbnd NH3+ of adsorbates are the strongest groups that interact with the surface of apatites, the adsorption is mainly due to the electrostatic interaction between the groups sbnd COOsbnd of amino acids and calcium Ca2+ ions of the apatite. Comparative study of interactions between adsorbates (L-lysine, DL-leucine and their mixture) and apatitic calcium phosphates is carried out in vitro by using UV-vis and infrared spectroscopy IR techniques.

Physiological and functional diversity of phenol degraders isolated from phenol-grown aerobic granules: Phenol degradation kinetics and trichloroethylene co-metabolic activities.

Science.gov (United States)

Zhang, Yi; Tay, Joo Hwa

2016-03-15

Aerobic granule is a novel form of microbial aggregate capable of degrading toxic and recalcitrant substances. Aerobic granules have been formed on phenol as the growth substrate, and used to co-metabolically degrade trichloroethylene (TCE), a synthetic solvent not supporting aerobic microbial growth. Granule formation process, rate limiting factors and the comprehensive toxic effects of phenol and TCE had been systematically studied. To further explore their potential at the level of microbial population and functions, phenol degraders were isolated and purified from mature granules in this study. Phenol and TCE degradation kinetics of 15 strains were determined, together with their TCE transformation capacities and other physiological characteristics. Isolation in the presence of phenol and TCE exerted stress on microbial populations, but the procedure was able to preserve their diversity. Wide variation was found with the isolates' kinetic behaviors, with the parameters often spanning 3 orders of magnitude. Haldane kinetics described phenol degradation well, and the isolates exhibited actual maximum phenol-dependent oxygen utilization rates of 9-449 mg DO g DW(-1) h(-1), in phenol concentration range of 4.8-406 mg L(-1). Both Michaelis-Menten and Haldane types were observed for TCE transformation, with the actual maximum rate of 1.04-21.1 mg TCE g DW(-1) h(-1) occurring between TCE concentrations of 0.42-4.90 mg L(-1). The TCE transformation capacities and growth yields on phenol ranged from 20-115 mg TCE g DW(-1) and 0.46-1.22 g DW g phenol(-1), respectively, resulting in TCE transformation yields of 10-70 mg TCE g phenol(-1). Contact angles of the isolates were between 34° and 82°, suggesting both hydrophobic and hydrophilic cell surface. The diversity in the isolates is a great advantage, as it enables granules to be versatile and adaptive under different operational conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating Marine Dissolved Organic Matter Fluorescence Transformations with Organic Geochemical Proxies in a Growth and Degradation Experiment using Amino Acids, Amino Sugars, and Phenols

Science.gov (United States)

Shields, M. R.; Bianchi, T. S.; Osburn, C. L.; Kinsey, J. D.; Ziervogel, K.; Schnetzer, A.

2017-12-01

The origin and mechanisms driving the formation of fluorescent dissolved organic matter (FDOM) in the open ocean remain unclear. Although recent studies have attempted to deconvolve the chemical composition and source of marine FDOM, these studies have been qualitative in nature. Here, we investigate these transformations using a more quantitative biomarker approach in a controlled growth and degradation experiment. In this experiment, a natural assemblage of phytoplankton was collected off the coast of North Carolina and incubated within roller bottles containing 0.2 µm-filtered North Atlantic surface water amended with f/2 nutrients. Samples were collected at the beginning (day 0), during exponential growth (day 13), stationary (day 20), and degradation (day 62) phases of the phytoplankton incubation. Amino acids, amino sugars, and phenolic compounds of the dissolved (DOM) were measured in conjunction with enzyme assays and bacterial counts to track shifts in OM quality as FDOM formed and was then transformed throughout the experiment. The results from the chemical analyses showed that the OM composition changed significantly from the initial and exponential phases to the stationary and degradation phases of the experiment. The percentage of aromatic amino acids to the total amino acid pool increased significantly during the exponential phase of phytoplankton growth, but then decreased significantly during the stationary and degradation phases. This increase was positively correlated to the fractional contribution of the protein-like peak in fluorescence to the total FDOM fluorescence. An increase in the concentration of amino acid degradation products during the stationary and degradation phases suggests that compositional changes in OM were driven by microbial transformation. This was further supported by a concurrent increase in total enzyme activity and increase in "humic-like" components of the FDOM. These findings link the properties and formation of FDOM

Differences in bioactivity of three endemic Nepeta species arising from main terpenoid and phenolic constituents

Directory of Open Access Journals (Sweden)

Nestorović-Živković Jasmina

2018-01-01

Full Text Available Methanol extracts of three endemic Nepeta species were analyzed for their main secondary metabolites, terpenes and phenolics, and further investigated for antioxidant capacity and embryonic toxicity in zebrafish. UHPLC/DAD/(± HESI-MS/MS analysis showed that the dominant compound in N. rtanjensis was trans,cis-nepetalactone, the cis,trans isomer of this monoterpene lactone was dominant in N. sibirica, while nepetalactone was detected only in traces in N. nervosa. In all investigated species, rosmarinic acid was the dominant phenolic compound, while other identified phenolic acids (chlorogenic, neochlorogenic and caffeic were present in considerably lower amounts. ABTS and DPPH assays showed that the methanol extracts of N. rtanjensis, N. sibirica and especially N. nervosa possessed strong antioxidant activities, with the FRAP assay revealing high ferric-reducing abilities for all three tested species. Such a strong antioxidant potential, especially as manifested in the DPPH and FRAP assays, can be attributed to phenolic acids, and in the first place to rosmarinic acid. Increased lethality of zebrafish embryos in any of the treatments was not observed, but several toxic effects on embryonic development were recorded, such as pericardial and yolk sac edema. As in other Nepeta species, the three studied endemic species possessed a great potential for food conservation or as medicinal supplements if applied in optimized concentrations; however, alternative sources of plant material (e.g. field cultivation should be established bearing in mind their vulnerability in nature.

Purification and properties of an O-acetyl-transferase from Escherichia coli that can O-acetylate polysialic acid sequences

International Nuclear Information System (INIS)

Higa, H.; Varki, A.

1986-01-01

Certain strains of bacteria synthesize an outer polysialic acid (K1) capsule. Some strains of K1 + E.coli are also capable of adding O-acetyl-esters to the exocyclic hydroxyl groups of the sialic acid residues. Both the capsule and the O-acetyl modification have been correlated with differences in antigenicity and pathogenicity. The authors have developed an assay for an O-acetyl-transferase in E.coli that transfers O-[ 3 H]acetyl groups from [ 3 H]acetyl-Coenzyme A to colominic acid (fragments of the polysialic acid capsule). Using this assay, the enzyme was solubilized, and purified ∼ 600-fold using a single affinity chromatography step with Procion Red-A Agarose. The enzyme also binds to Coenzyme A Sepharose, and can be eluted with high salt or Coenzyme A. The partially purified enzyme has a pH optimum of 7.0 - 7.5, is unaffected by divalent cations, is inhibited by high salt concentrations, is inhibited by Coenzyme A (50% inhibition at 100 μM), and shows an apparent Km for colominic acid of 3.7 mM (sialic acid concentration). This enzyme could be involved in the O-acetyl +/- form variation seen in some strains of K1 + E.coli

Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid

International Nuclear Information System (INIS)

Nye, Jonathon A.; Jarkas, Nashwa; Schuster, David M.; Savir-Baruch, Bital; Voll, Ronald J.; Camp, Vernon M.; Goodman, Mark M.

2011-01-01

Introduction: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[ 18 F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[ 18 F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans. Methods: A DU145 xenograft rodent model was used to measure anti-2-[ 18 F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[ 18 F]FACPC-1 toxicity was assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247±61 MBq bolus injection of anti-2-[ 18 F]FACPC-1. Estimates of radiation dose from anti-2-[ 18 F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software. Results: High anti-2-[ 18 F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[ 18 F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq. Conclusion: Anti-2-[ 18 F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting malignant tissues in these regions.

Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 10

International Nuclear Information System (INIS)

Gruhn, K.; Hennig, A.

1989-01-01

Over a period of 4 days 12 colostomized laying hens daily received 36 g coarse wheat meal containing 14.37 atom-% 15 N excess ( 15 N') together with a conventional ration. After the homogenisation of each oviduct N and 15 N' were determined. After the precipitation with TCA the 15 N' of the amino acids was analysed in both the precipitate and the supernatant. In addition, the free amino acids and the peptides were determined in the TCA soluble fraction. The atom-% 15 N' in the total N and in the non-basic amino acid N showed a parallel decrease; it diminshed from 1.75 atom-% 15 N' to 0.64. Of the three basic amino acids, lysine shows the lowest labelling at all four measuring points. The quotas of non-basic amino acid 14 N and 15 N' in the total 14 N and 15 N' of the oviduct are the same and amount to 53%. In contrast to this, the quota of the 14 N of the basic amino acids in the total 14 N of the oviduct only amounts to 21.6% and that of 15 N' only to 15.4%. The average atom-% 15 N' of the free amino acids 12 h after the last 15 N application is 1.54 and is considerably above that of the peptides with 1.15 atom-% 15 N'. 36 h after the last 15 N application the ascertained value of 1.25 is identical in both fractions. The labelling of the free amino acids decreases more quickly than that of the peptides the more time has passed after the last 15 N application. (author)

Key mediators of intracellular amino acids signaling to mTORC1 activation.

Science.gov (United States)

Duan, Yehui; Li, Fengna; Tan, Kunrong; Liu, Hongnan; Li, Yinghui; Liu, Yingying; Kong, Xiangfeng; Tang, Yulong; Wu, Guoyao; Yin, Yulong

2015-05-01

Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.

Molecular level biodegradation of phenol and its derivatives through dmp operon of Pseudomonas putida: A bio-molecular modeling and docking analysis.

Science.gov (United States)

Ray, Sujay; Banerjee, Arundhati

2015-10-01

Participation of Pseudomonas putida-derived methyl phenol (dmp) operon and DmpR protein in the biodegradation of phenol or other harmful, organic, toxic pollutants was investigated at a molecular level. Documentation documents that P. putida has DmpR protein which positively regulates dmp operon in the presence of inducers; like phenols. From the operon, phenol hydroxylase encoded by dmpN gene, participates in degrading phenols after dmp operon is expressed. For the purpose, the 3-D models of the four domains from DmpR protein and of the DNA sequences from the two Upstream Activation Sequences (UAS) present at the promoter region of the operon were demonstrated using discrete molecular modeling techniques. The best modeled structures satisfying their stereo-chemical properties were selected in each of the cases. To stabilize the individual structures, energy optimization was performed. In the presence of inducers, probable interactions among domains and then the two independent DNA structures with the fourth domain were perused by manifold molecular docking simulations. The complex structures were made to be stable by minimizing their overall energy. Responsible amino acid residues, nucleotide bases and binding patterns for the biodegradation, were examined. In the presence of the inducers, the biodegradation process is initiated by the interaction of phe50 from the first protein domain with the inducers. Only after the interaction of the last domain with the DNA sequences individually, the operon is expressed. This novel residue level study is paramount for initiating transcription in the operon; thereby leading to expression of phenol hydroxylase followed by phenol biodegradation. Copyright © 2015. Published by Elsevier B.V.

Non-protein amino acids in Australian acacia seed: implications for food security and recommended processing methods to reduce djenkolic acid.

Science.gov (United States)

Boughton, Berin A; Reddy, Priyanka; Boland, Martin P; Roessner, Ute; Yates, Peter

2015-07-15

Seed of Australian acacia species, Acacia colei, Acacia elecantha, Acacia torulosa, Acacia turmida and Acacia saligna, were analysed for the presence of toxic non-protein amino acids and the levels of essential amino acids. Amines were derivatised with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate before analysis using liquid chromatography electrospray ionisation triple quadrupole mass spectrometry (LC-ESI-QQQ-MS). Multiple reaction monitoring (MRM) with optimised transitions and collision energies for each analyte were employed. The known nephrotoxic compound djenkolic acid was found to be present at elevated levels in all species tested. The lowest levels were in A. colei (0.49% w/w) and the highest in A. saligna (1.85% w/w). Observed levels of djenkolic acid are comparable to measured and reported levels found in the djenkol bean. Subsequent testing of seed processing methods showed djenkolic acid levels can be significantly reduced by over 90% by dry roasting at 180 °C rendering the seed safe for human consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanisms of amino acid sensing in mTOR signaling pathway

OpenAIRE

Kim, Eunjung

2009-01-01

Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including ca...

Synthesis, characterization and toxicity of azanonaborane-containing imidazoles for boron neutron capture therapy

International Nuclear Information System (INIS)

El-Zaria, Mohamed E.; Genady, Afaf R.; Gabel, Detlef

2006-01-01

The exo-NH 2 R group of the azanonaborane of the type [(RH 2 N)B 8 H 11 NHR] can be exchanged by one hetero-nitrogen atom of the imidazole ring. In the case of histamine, the exchange takes place on the aliphatic amino group, the hetero-nitrogen atom of the imidazole ring or both of them. In vitro experiments using B16 melanoma cells showed that incorporation of B 8 N cluster unit into primary amino group of the histamine increases the compound's toxicity. In contrast, this specificity for cytotoxicity effect was not observed in the case of histamine containing two B 8 N clusters which was relatively nontoxic and did not inhibit colony formation up to 2 mM. (author)

Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

Science.gov (United States)

Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P

2015-01-01

Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.

Inhibition of dehydrogenase activity in petroleum refinery wastewater bacteria by phenolic compounds

Directory of Open Access Journals (Sweden)

Gideon C. Okpokwasili

2010-04-01

Full Text Available The toxicity of phenol, 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2-chlorophenol, 4-chlorophenol, 4-bromophenol and 3,5-dimethylphenol on Pseudomonas, Bacillus and Escherichia species isolated from petroleum refinery wastewater was assessed via inhibition of dehydrogenase enzyme activity. At low concentrations, 2-nitrophenol, 2-chlorophenol, 4-chlorophenol, 4-bromophenol and 3,5-dimethylphenol stimulated dehydrogenase activity and at sufficient concentrations, phenolic compounds inhibited dehydrogenase activities. Generally, phenol is less toxic than substituted phenols. Estimations of the degree of inhibition/stimulation of dehydrogenase activities showed significant dose-dependent responses that are describable by logistic functions. The toxicity thresholds varied significantly (P < 0.05 among the bacterial strains and phenolic compounds. The median inhibitory concentrations (IC50s ranged from 4.118 ± 0.097 mg.L-1 for 4-nitrophenol against Pseudomonas sp. DAF1 to 1407.997 ± 7.091 mg.L-1 for phenol against Bacillus sp. DISK1. This study suggested that the organisms have moderate sensitivity to phenols and have the potential to be used as indicators for assessment of chemical toxicity. They could also be used as catalysts for degradation of phenols in effluents.

Construction of a mutant of Actinoplanes sp. N902-109 that produces a new rapamycin analog.

Science.gov (United States)

Huang, He; Gao, Ping; Zhao, Qi; Hu, Hai-Feng

2018-03-01

In the present study, we introduced point mutations into Ac_rapA which encodes a polyketide synthase responsible for rapamycin biosynthesis in Actinoplanes sp. N902-109, in order to construct a mutant with an inactivated enoylreductase (ER) domain, which was able to synthesize a new rapamycin analog. Based on the homologous recombination induced by double-strand breaks in chromosome mediated by endonuclease I-SceI, the site-directed mutation in the first ER domain of Ac_rapA was introduced using non-replicating plasmid pLYERIA combined with an I-SceI expression plasmid. Three amino acid residues of the active center, Ala-Gly-Gly, were converted to Ala-Ser-Pro. The broth of the mutant strain SIPI-027 was analyzed by HPLC and a new peak with the similar UV spectrum to that of rapamycin was found. The sample of the new peak was prepared by solvent extraction, column chromatography, and crystallization methods. The structure of new compound, named as SIPI-rapxin, was elucidated by determining and analyzing its MS and NMR spectra and its biological activity was assessed using mixed lymphocyte reaction (MLR). An ER domain-deficient mutant of Actinoplanes sp. N902-109, named as SIPI-027, was constructed, which produced a novel rapamycin analog SIPI-rapxin and its structure was elucidated to be 35, 36-didehydro-27-O-demethylrapamycin. The biological activity of SIPI-rapxin was better than that of rapamycin. In conclusion, inactivation of the first ER domain of rapA, one of the modular polyketide synthase responsible for macro-lactone synthesis of rapamycin, gave rise to a mutant capable of producing a novel rapamycin analog, 35, 36-didehydro-27-O-demethylrapamycin, demonstrating that the enoylreductase domain was responsible for the reduction of the double bond between C-35 and C-36 during rapamycin synthesis. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Neurotoxic Alkaloids: Saxitoxin and Its Analogs

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Troco K. Mihali

2010-07-01

Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

Science.gov (United States)

Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

2018-03-01

Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

Science.gov (United States)

Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

2015-09-01

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. Copyright © 2015, Pisithkul et al.

Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis

Science.gov (United States)

Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; Stevenson, David M.

2015-01-01

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

Production of N-acetyl-D-neuraminic acid using two sequential enzymes overexpressed as double-tagged fusion proteins

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Cheng Chung-Hsien

2009-07-01

Full Text Available Abstract Background Two sequential enzymes in the production of sialic acids, N-acetyl-D-glucosamine 2-epimerase (GlcNAc 2-epimerase and N-acetyl-D-neuraminic acid aldolase (Neu5Ac aldolase, were overexpressed as double-tagged gene fusions. Both were tagged with glutathione S-transferase (GST at the N-terminus, but at the C-terminus, one was tagged with five contiguous aspartate residues (5D, and the other with five contiguous arginine residues (5R. Results Both fusion proteins were overexpressed in Escherichia coli and retained enzymatic activity. The fusions were designed so their surfaces were charged under enzyme reaction conditions, which allowed isolation and immobilization in a single step, through a simple capture with either an anionic or a cationic exchanger (Sepharose Q or Sepharose SP that electrostatically bound the 5D or 5R tag. The introduction of double tags only marginally altered the affinity of the enzymes for their substrates, and the double-tagged proteins were enzymatically active in both soluble and immobilized forms. Combined use of the fusion proteins led to the production of N-acetyl-D-neuraminic acid (Neu5Ac from N-acetyl-D-glucosamine (GlcNAc. Conclusion Double-tagged gene fusions were overexpressed to yield two enzymes that perform sequential steps in sialic acid synthesis. The proteins were easily immobilized via ionic tags onto ionic exchange resins and could thus be purified by direct capture from crude protein extracts. The immobilized, double-tagged proteins were effective for one-pot enzymatic production of sialic acid.

Treatment with paracetamol in infants

DEFF Research Database (Denmark)

Arana, A; Morton, N S; Hansen, Tom Giedsing

2001-01-01

Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has become the most widely used analgesic and antipyretic in children. However, there is a wide discrepancy between the extent to which paracetamol is used and the limited available pharmacological data in small infants. The purpose...... of this article is to present a review of the current literature regarding the use of paracetamol in neonates and infants with a particular emphasis on pharmacological issues....

Sorption of phenol and phenol derivatives in hydrotalcite

International Nuclear Information System (INIS)

Avina G, E.I.

2002-01-01

One of the main problems in Mexico and in the World is the waste water pollution of a great variety of industrial processes by organic compounds. Among those ones the phenol compounds which are highly toxic, refractories (to the chemical degradation) and poorly biodegradable. This is due in a large extent to the problem created by the accelerated increase in the environmental pollution in the cities and industrial centers. The phenol compounds are used in a great variety of industries such as the production of resins, plasticizers, antioxidants, pesticides, colourings, disinfectants, etc. These phenol compounds are specially harmful, since they have repercussions on the flora of plants of biological treatment of water affecting its operation. The main objective of this work is to evaluate the capacities of phenol detention and its derivatives in an hydrotalcite type compound and diminishing with it the presence in water, in this case, of solutions prepared in the laboratory. In order to analyse this elimination process was used a methodology based in the carrying out in batch experiments and in the elaboration of a sorption isotherm. It is worth pointing out that this work was realized at laboratory scale, at relatively high phenol concentration ratio. With the obtained results when the sorption properties are evaluated the calcined hydrotalcite (HTC) for detaining phenol and p-chloro phenol it was observed that it is detained greater quantity of p-chloro phenol than phenol in the HTC. The detention of these phenol compounds in the HTC is due to the memory effect by the hydrotalcite regeneration starting from the oxides which are formed by the burning material. (Author)

Formation of H2O2 at UV-photolysis of water solutions of phenol

International Nuclear Information System (INIS)

Guliyeva, U.A.; Gurbanov, M.A.; Mahmudov, H.M.

2013-01-01

Non-traditional methods, based on application of ionizing and UV-radiation widely used for cleaning of water solutions from toxic substances, including phenols. These methods have simultaneously effect including of disinfection and chemical cleaning of water solutions from various industrial processes

Functionalized 2′-amino-α-L-LNA

DEFF Research Database (Denmark)

Kumar, T. Santhosh; Madsen, Andreas Stahl; Østergaard, Michael

2009-01-01

Chemically modified oligonucleotides are increasingly applied in nucleic acid based therapeutics and diagnostics. LNA (locked nucleic acid) and its diastereomer α-L-LNA are two promising examples thereof that exhibit increased thermal and enzymatic stability. Herein, the synthesis, biophysical......′-functionalities such as 2′-N-acetyl-2′-amino-α-L-LNA (monomer V) had detrimental effects on thermal affinity toward DNA/RNA complements with decreases of as much as -16.5 °C per modification. Extensive thermal DNA selectivity, favorable entropic contributions upon duplex formation, hybridization...

Phenol Removal by a Novel Non-Photo-Dependent Semiconductor Catalyst in a Pilot-Scaled Study: Effects of Initial Phenol Concentration, Light, and Catalyst Loading

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Xiao Chen

2014-01-01

Full Text Available A novel non-photo-dependent semiconductor catalyst (CT was employed to degrade phenol in the present pilot-scaled study. Effect of operational parameters such as phenol initial concentration, light area, and catalyst loading on phenol degradation, was compared between CT catalyst and the conventional photocatalyst titanium dioxide. CT catalyst excelled titanium dioxide in treating and mineralizing low-level phenol, under both mild UV radiation and thunder conditions of nonphoton. The result suggested that CT catalyst could be applied in circumstances when light is not easily accessible in pollutant-carrying media (e.g., particles, cloudy water, and colored water.

Preferential hydrophobic interactions are responsible for a preference of D-amino acids in the aminoacylation of 5'-AMP with hydrophobic amino acids

Science.gov (United States)

Lacey, J. C. Jr; Wickramasinghe, N. S.; Sabatini, R. S.

1992-01-01

We have studied the chemistry of aminoacyl AMP to model reactions at the 3' terminus of aminoacyl tRNA for the purpose of understanding the origin of protein synthesis. The present studies relate to the D, L preference in the esterification of 5'-AMP. All N-acetyl amino acids we studied showed faster reaction of the D-isomer, with a generally decreasing preference for D-isomer as the hydrophobicity of the amino acid decreased. The beta-branched amino acids, Ile and Val, showed an extreme preference for D-isomer. Ac-Leu, the gamma-branched amino acid, showed a slightly low D/L ratio relative to its hydrophobicity. The molecular basis for these preferences for D-isomer is understandable in the light of our previous studies and seems to be due to preferential hydrophobic interaction of the D-isomer with adenine. The preference for hydrophobic D-amino acids can be decreased by addition of an organic solvent to the reaction medium. Conversely, peptidylation with Ac-PhePhe shows a preference for the LL isomer over the DD isomer.

Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene

Energy Technology Data Exchange (ETDEWEB)

Irving, Roy M. [Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States); Pinkerton, Marie E. [Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706 (United States); Elfarra, Adnan A., E-mail: elfarra@svm.vetmed.wisc.edu [Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States); Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706 (United States)

2013-02-15

N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague–Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S{sub 2}–S{sub 3} segments) while DCVCS primarily affected the outer cortical proximal tubules (S{sub 1}–S{sub 2} segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37 °C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity. - Highlights: ► NA-DCVCS and NA-DCVC toxicity are distinct from DCVCS toxicity. ► NA-DCVCS readily reacts with GSH to form mono- and di-GSH conjugates. ► Liver glutathione S-transferases enhance NA-DCVCS GSH conjugate formation. ► Renal localization of lesions suggests a role for NA-DCVCS in TCE nephrotoxicity.

Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene

International Nuclear Information System (INIS)

Irving, Roy M.; Pinkerton, Marie E.; Elfarra, Adnan A.

2013-01-01

N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague–Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S 2 –S 3 segments) while DCVCS primarily affected the outer cortical proximal tubules (S 1 –S 2 segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37 °C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity. - Highlights: ► NA-DCVCS and NA-DCVC toxicity are distinct from DCVCS toxicity. ► NA-DCVCS readily reacts with GSH to form mono- and di-GSH conjugates. ► Liver glutathione S-transferases enhance NA-DCVCS GSH conjugate formation. ► Renal localization of lesions suggests a role for NA-DCVCS in TCE nephrotoxicity

N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects

Science.gov (United States)

Varland, Sylvia; Osberg, Camilla; Arnesen, Thomas

2015-01-01

The vast majority of eukaryotic proteins are N-terminally modified by one or more processing enzymes. Enzymes acting on the very first amino acid of a polypeptide include different peptidases, transferases, and ligases. Methionine aminopeptidases excise the initiator methionine leaving the nascent polypeptide with a newly exposed amino acid that may be further modified. N-terminal acetyl-, methyl-, myristoyl-, and palmitoyltransferases may attach an acetyl, methyl, myristoyl, or palmitoyl group, respectively, to the α-amino group of the target protein N-terminus. With the action of ubiquitin ligases, one or several ubiquitin molecules are transferred, and hence, constitute the N-terminal modification. Modifications at protein N-termini represent an important contribution to proteomic diversity and complexity, and are essential for protein regulation and cellular signaling. Consequently, dysregulation of the N-terminal modifying enzymes is implicated in human diseases. We here review the different protein N-terminal modifications occurring co- or post-translationally with emphasis on the responsible enzymes and their substrate specificities. PMID:25914051

Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

Science.gov (United States)

Pontikis, R; Benhida, R; Aubertin, A M; Grierson, D S; Monneret, C

1997-06-06

A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6-(arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.

Synthesis and biological activity of M6-P and M6-P analogs on fibroblast and keratinocyte proliferation.

Science.gov (United States)

Clavel, Caroline; Barragan-Montero, Véronique; Garric, Xavier; Molès, Jean-Pierre; Montero, Jean-Louis

2005-09-01

A new synthetic route to obtain the carboxylate analog of mannose 6-phosphate (M6-P) is presented. The effects of the M6-P, the carboxylate and two other analogs (the phosphonate and the alpha,beta ethylenic carboxylate) on the proliferation of human keratinocytes and dermal fibroblasts as well as on the proliferation of a murine fibroblast cell line, 3T3-J2 are tested. We observed that M6-P is a potent inhibitor of proliferation of both fibroblasts and keratinocytes. Among its analogs, the phosphonate showed a similar effect on human dermal fibroblasts but not on keratinocytes.

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies.

Science.gov (United States)

Kim, Kyu-pyo; Park, Seong Joon; Kim, Jeong-Eun; Hong, Yong Sang; Lee, Jae-Lyun; Bae, Kyun-Seop; Cha, Hyunju; Kwon, Sool-Ki; Ro, Seonggu; Cho, JoongMyung; Kim, Tae Won

2015-10-01

The aim of the present study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of single and multiple doses of intravenous CG200745, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. Two to six patients received intravenous CG200745 according to the 2 + 4 dose-escalating method. This first-in-human trial was comprised of two parts: Part 1 was a single ascending dose, and Part 2 was multiple ascending doses weekly for 3 weeks, and then 1 week off. For the first cycle, pharmacokinetic sampling for CG200745 and pharmacodynamic sampling for acetylated histone H4 in peripheral blood mononuclear cells (PBMCs) were performed on day 1 for Part 1 and on days 1 and 15 for Part 2. Examination of acetylated histone H4 in pre- and post-biopsy samples was performed in accessible patients. In all, 28 patients were treated at 13 dose levels (1.8-250 mg/m(2)) and received a total of 71 cycles of CG200745. Hematologic toxicities included grade 3/4 neutropenia (22.2 %) that did not last a week and non-hematologic toxicities included fatigue (22.2 %) and anorexia (16.7 %) that did not exceed grade 2. No dose-limiting toxic effects were noted. Dose proportionality was observed for both the maximum concentration and area under the curve. The elimination half-life was 5.67 ± 2.69 h (mean ± standard deviation). An increase in PBMC acetylated histone H4 was observed at dose levels up to 51 mg/m(2), which plateaued at higher dose levels. At 24 h, 75 % of patients (6/8) showed higher relative acetylation in tumor tissue compared to PBMCs. Although there was no partial or complete response, 57.1 % of patients (16/28) had stable disease that lasted at least 6 weeks. CG200745 can be safely administered at effective dose levels that inhibit HDAC in PBMCs and tumor tissue. Although MTD was not reached, further escalation was not performed because acetylated histone H4 plateaued at dose

Importance of phenols structure on their activity as antinitrosating agents: A kinetic study

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Marcia Pessego

2011-01-01

Full Text Available Objective : Nitrosative deamination of DNA bases induced by reaction with reactive nitrogen species (RNS has been pointed out as a probable cause of mutagenesis. (Polyphenols, present in many food items from the Mediterranean diet, are believed to possess antinitrosating properties due to their RNS scavenging ability, which seems to be related to their structure. It has been suggested that phenolic compounds will react with the above-mentioned species more rapidly than most amino compounds, thus preventing direct nitrosation of the DNA bases and their transnitrosation from endogenous N-nitroso compounds, or most likely from the transient N-nitrosocompounds formed in vivo. Materials and Methods : In order to prove that assumption, a kinetic study of the nitroso group transfer from a N-methyl-N-nitrosobenzenesulfonamide (N-methyl-N-nitroso-4-methylbenzenesulfonamide, MeNMBS to the DNA bases bearing an amine group and to a series of phenols was carried out. In the transnitrosation of phenols, the formation of nitrosophenol was monitored by Ultraviolet (UV / Visible spectroscopy, and in the reactions of the DNA bases, the consumption of MeNMBS was followed by high performance liquid chromatography (HPLC. Results : The results obtained point to the transnitrosation of DNA bases being negligible, as well as that of phenols bearing electron-withdrawing groups. Phenols with methoxy substituents in positions 2, 4, and / or 6, although they seemed to react, did not afford the expected product. Phenols with electron-releasing substituents, unless these blocked the oxygen atom, reacted with our model compound at an appreciable rate. O-nitrosation of the phenolate ion followed by rearrangement of the C-nitrosophenol seemed to be involved. Conclusion : This study provided evidence that the above compounds might actually act as antinitrosating agents in vivo.

Skin metabolism of aminophenols: Human keratinocytes as a suitable in vitro model to qualitatively predict the dermal transformation of 4-amino-2-hydroxytoluene in vivo

International Nuclear Information System (INIS)

Goebel, C.; Hewitt, N.J.; Kunze, G.; Wenker, M.; Hein, D.W.; Beck, H.; Skare, J.

2009-01-01

4-Amino-2-hydroxytolune (AHT) is an aromatic amine ingredient in oxidative hair colouring products. As skin contact occurs during hair dyeing, characterisation of dermal metabolism is important for the safety assessment of this chemical class. We have compared the metabolism of AHT in the human keratinocyte cell line HaCaT with that observed ex-vivo in human skin and in vivo (topical application versus oral (p.o.) and intravenous (i.v.) route). Three major metabolites of AHT were excreted, i.e. N-acetyl-AHT, AHT-sulfate and AHT-glucuronide. When 12.5 mg/kg AHT was applied topically, the relative amounts of each metabolite were altered such that N-acetyl-AHT product was the major metabolite (66% of the dose in comparison with 37% and 32% of the same applied dose after i.v. and p.o. administration, respectively). N-acetylated products were the only metabolites detected in HaCaT cells and ex-vivo whole human skin discs for AHT and p-aminophenol (PAP), an aromatic amine known to undergo N-acetylation in vivo. Since N-acetyltransferase 1 (NAT1) is the responsible enzyme, kinetics of AHT was further compared to the standard NAT1 substrate p-aminobenzoic acid (PABA) in the HaCaT model revealing similar values for K m and V max . In conclusion NAT1 dependent dermal N-acetylation of AHT represents a 'first-pass' metabolism effect in the skin prior to entering the systemic circulation. Since the HaCaT cell model represents a suitable in vitro assay for addressing the qualitative contribution of the skin to the metabolism of topically-applied aromatic amines it may contribute to a reduction in animal testing

Evaluation of the Efficiency of a Biofilter System’s Phenol Removal From Wastewater

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Reza Shokoohi

2016-06-01

Full Text Available Phenol is a toxic hydrocarbon that has been found in the wastewater of several industries, including the petroleum and petrochemical industries. The discharge of untreated wastewater from these industries causes environmental pollution, especially in water. The aim of this study was to evaluate the efficiency of phenol removal from wastewater using a biofiltration system. In this experimental study, a cylindrical plexiglass biofilter reactor with an effective volume of 12 liters was used. A total of 30 pcs of plastic grid discs were placed inside the reactor by plastic pipes to maintain the biofilm media in the reactor. The microorganisms used in this study were obtained from the biological sludge of a municipal wastewater treatment plant. The reproduction and adaptation of the microorganisms to 500 mg/L of phenol lasted three months. The effects of pH, phenol, nitrogen, phosphorus, glucose concentration, and hydraulic retention time on the biofilter system’s performance was evaluated. The results of this study showed that in optimal conditions, this system can reduce the phenol concentration from 500 mg/L to zero within about 4 hr. Maximum efficiency occurred in pH = 7, and the proper COD/N/P ratio was 100/10/2, respectively. In general, this biofilter system is capable of removing 500 mg/L of phenol concentrations and an organic load of 4 - 4.5 kg COD/m3.d within 4 - 5 hr. with high efficiency.

X-ray structure of a transition state analog complex reveals the molecular origins of the catalytic power and substrate specificity of acetylcholinesterase

Energy Technology Data Exchange (ETDEWEB)

Harel, M.; Silman, I. [Weizmann Inst. of Science, Rehovot (Israel); Quinn, D.M.; Nair, H.K. [Univ. of Iowa, Iowa City, IA (United States); Sussman, J.L. [Weizmann Inst. of Science, Rehovot (Israel)]|[Brookhaven National Lab., Upton, NY (United States)

1996-03-13

The structure of a complex of Torpedo californica acetylcholinesterase with the transition state analog inhibitor m-(N, N,N-trimethylammonio)-2,2,2-trifluoroacetophenone has been solved by X-ray crystallographic methods to 2.8 A resolution. Since the inhibitor binds to the enzyme about 10{sup 10}-fold more tightly than the substrate acetylcholine, this complex provides a visual accounting of the enzyme-ligand interactions that provide the molecular basis for the catalytic power of acetylcholinesterase. The acetyl ester hydrolytic specificity of the enzyme is revealed by the interaction of the CF{sub 3} function of the transition state analog with a concave binding site comprised of the residues G119, W233, F288, F290, and F331. The highly geometrically convergent array of enzyme-ligand interactions visualized in the complex described herein envelopes the acylation transition state and sequesters it from solvent, this being consistent with the location of the active site at the bottom of a deep and narrow gorge. 82 refs., 5 figs.

Antioxidant Capacity, Phenolic Constituents and Toxicity of Hot Water Extract from Red Maple Buds.

Science.gov (United States)

Meda, Naamwin R; Poubelle, Patrice E; Stevanovic, Tatjana

2017-06-01

The present study reports, for the first time, the results of the antioxidant capacity and the phenolic composition of a hot water extract from red maple buds (RMB), as well as its safety. In this regard and comparatively to antioxidant standards, this extract exhibits a significant antiradical capacity when tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH · ) and anion superoxide trapping assays. High-resolution mass spectrometric and nuclear magnetic resonance analyses permitted to determine for the first time, in red maple species, cyanidin-3-O-glucoside, quercetin-3-O-galactoside, quercetin-3-O-arabinoside, and quercetin. Also, the quantification of individual phenolics by high-performance liquid chromatography method revealed that ginnalin A at 117.0 mg/g is the major compound of RMB hot water extract. Finally, using flow cytometry evaluation, the extract of RMB was determined to have no toxicity neither to cause significant modification of apoptosis process, up to concentration of 100 μg/ml, on human peripheral blood neutrophils. These results allow anticipating various fields of application of RMB water extract. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Non-Toxic Orbiter Maneuvering System (OMS) and Reaction Control System

Science.gov (United States)

Hurlbert, Eric A.; Nicholson, Leonard S. (Technical Monitor)

1999-01-01

NASA is pursuing the technology and advanced development of a non-toxic (NT) orbital maneuvering system (OMS) and reaction control system (RCS) for shuttle upgrades, RLV, and reusable first stages. The primary objectives of the shuttle upgrades program are improved safety, improved reliability, reduced operations time and cost, improved performance or capabilities, and commonality with future space exploration needs. Non-Toxic OMS/RCS offers advantages in each of these categories. A non-toxic OMS/RCS eliminates the ground hazards and the flight safety hazards of the toxic and corrosive propellants. The cost savings for ground operations are over $24M per year for 7 flights, and the savings increase with increasing flight rate up to $44M per year. The OMS/RCS serial processing time is reduced from 65 days to 13 days. The payload capability can be increased up to 5100 Ibms. The non-toxic OMS/RCS also provides improved space station reboost capability up to 20 nautical miles over the current toxic system of 14 nautical miles. A NT OMS/RCS represents a clear advancement in the SOA over MMH/NTO. Liquid oxygen and ethanol are clean burning, high-density propellants that provide a high degree of commonality with other spacecraft subsystems including life support, power, and thermal control, and with future human exploration and development of space missions. The simple and reliable pressure-fed design uses sub-cooled liquid oxygen at 250 to 350 psia, which allows a propellant to remain cryogenic for longer periods of time. The key technologies are thermal insulation and conditioning techniques are used to maintain the sub-cooling. Phase I successfully defined the system architecture, designed an integrated OMS/RCS propellant tank, analyzed the feed system, built and tested the 870 lbf RCS thrusters, and tested the 6000 lbf OMS engine. Phase 11 is currently being planned for the development and test of full-scale prototype of the system in 1999 and 2000

Iodate oxidation of N-Acetyl L-Cysteine: Application in drug determination and characterization of its oxidation and degradation product by mass spectrometry

International Nuclear Information System (INIS)

Siddiqui, Masom Raza; Wabaiduri, Saikh Mohammas; Alothman, Zied A; Rahman, Habibur; Alam, Sarfarah; Ali, Sajid

2014-01-01

A kinetic spectrophotometric method based on the initial rate measurement has been developed for the determination of N-acetyl L-cysteine. The developed method is based on the oxidation of N-acetyl L-cysteine with iodate. The reaction product was studied and characterized using the mass spectrometry and the structure of the product was proposed. From the mass spectrometric studies it was concluded that the oxidation of the drug resulted in the formation of a disulfide. The developed method was validated as per the guidelines of international conference on harmonization. The developed initial rate method was found to be linear in the concentration range of 1.25 - 30μg ml-1. The detection and quantitation limits were found to be 0.018 and 0.056 μG ml -1 . In the current study, the degradation product of N-acetyl L cysteine was also prepared and identified using mass spectrometry. Keywords: N- acetyl cysteine, Initial rate method, Spectrophotometry, mass spectrometry

A Novel Non-Toxic Xylene Substitute (SBO) for Histology

OpenAIRE

Kunhua, Wang; Chuming, Fan; Tao, Lai; Yanmei, Yang; Xin, Yang; Xiaoming, Zhang; Xuezhong, Guo; Xun, Lai

2011-01-01

Xylene has been generally used as a clearing and deparaffinizing agent in histology. Because of the potential toxic and flammable nature of xylene, its substitutes have been introduced into some laboratories. In this study, we introduced a novel, non-toxic xylene substitute (SBO), which was generated through a mixture of 86% of white oil No.2 and 14% of N-heptane. SBO had a high boiling point (188°C) and flash point (144°C) coupled with a scentless and decreased volatility. To compare the eff...

The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl-DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate

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Clemens Schmeitzl

2015-08-01

Full Text Available Deoxynivalenol (DON is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON, 15-acetyl-DON (15-ADON and 3,15-diacetyl-DON (3,15-diADON, and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-β-D-glucoside (D15G and of 15-acetyl-DON-3-sulfate (15-ADON3S as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-β-D-glucoside (15-ADON3G is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3-O-β-D-glucoside (D3G. This study highlights significant differences in the metabolization of DON and its acetylated derivatives.

β-Amino-n-butyric Acid Regulates Seedling Growth and Disease Resistance of Kimchi Cabbage

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Yeong Chae Kim

2013-09-01

Full Text Available Non-protein amino acid, β-amino-n-butyric acid (BABA, has been involved in diverse physiological processes including seedling growth, stress tolerance and disease resistance of many plant species. In the current study, treatment of kimchi cabbage seedlings with BABA significantly reduced primary root elongation and cotyledon development in a dose-dependent manner, which adverse effects were similar to the plant response to exogenous abscisic acid (ABA application. BABA was synergistically contributing ABA-induced growth arrest during the early seedling development. Kimchi cabbage leaves were highly damaged and seedling growth was delayed by foliar spraying with high concentrations of BABA (10 to 20 mM. BABA played roles differentially in in vitro fungal conidial germination, mycelial growth and conidation of necrotroph Alternaria brassicicola causing black spot disease and hemibiotroph Colletotrichum higginsianum causing anthracnose. Pretreatment with BABA conferred induced resistance of the kimchi cabbage against challenges by the two different classes of fungal pathogens in a dose-dependent manner. These results suggest that BABA is involved in plant development, fungal development as well as induced fungal disease resistance of kimchi cabbage plant.

Developing selective histone deacetylases (HDACs) inhibitors through ebselen and analogs.

Science.gov (United States)

Wang, Yuren; Wallach, Jason; Duane, Stephanie; Wang, Yuan; Wu, Jianghong; Wang, Jeffrey; Adejare, Adeboye; Ma, Haiching

2017-01-01

Histone deacetylases (HDACs) are key regulators of gene expression in cells and have been investigated as important therapeutic targets for cancer and other diseases. Different subtypes of HDACs appear to play disparate roles in the cells and are associated with specific diseases. Therefore, substantial effort has been made to develop subtype-selective HDAC inhibitors. In an effort to discover existing scaffolds with HDAC inhibitory activity, we screened a drug library approved by the US Food and Drug Administration and a National Institutes of Health Clinical Collection compound library in HDAC enzymatic assays. Ebselen, a clinical safe compound, was identified as a weak inhibitor of several HDACs, including HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9 with half maximal inhibitory concentrations approximately single digit of µM. Two ebselen analogs, ebselen oxide and ebsulfur (a diselenide analog of ebselen), also inhibited these HDACs, however with improved potencies on HDAC8. Benzisothiazol, the core structure of ebsulfur, specifically inhibited HDAC6 at a single digit of µM but had no inhibition on other HDACs. Further efforts on structure-activity relationship based on the core structure of ebsulfur led to the discovery of a novel class of potent and selective HDAC6 inhibitors with RBC-2008 as the lead compound with single-digit nM potency. This class of histone deacetylase inhibitor features a novel pharmacophore with an ebsulfur scaffold selectively targeting HDAC6. Consistent with its inhibition on HDAC6, RBC-2008 significantly increased the acetylation levels of α-tubulin in PC-3 cells. Furthermore, treatment with these compounds led to cell death of multiple tumor cell lines in a dose-dependent manner. These results demonstrated that ebselen and ebsulfur analogs are inhibitors of HDACs, supporting further preclinical development of this class of compounds for potential therapeutic applications.

Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

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Paul B. Tchounwou

2005-04-01

Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

Evaluation of gels obtained from acetylation of chitosan in heterogeneous medium

International Nuclear Information System (INIS)

Garcia, Rosangela Balaban; Silva, Dayse Luzia Pinheiro da; Costa, Marta

2008-01-01

Chitosan was acetylated during 2, 5 and 10 h and physical gels were obtained at different polymer concentrations in N,N-dimethylacetamide containing 5% of LiCl. Acetylation was confirmed by infrared spectroscopy and 13 C NMR, and degrees of acetylation in the range of 0.82-0.91 were determined by NMR. The O-acetylation degree (0.12-0.15) was exclusively determined by a volumetric method. Rheological studies showed that the storage modulus values were smaller for the more acetylated samples and increased with the temperature and the polymer concentration. All the gels presented storage modulus superior to loss modulus, evidencing more elastic than viscous characteristics. The results obtained in this work suggest a gelation process based on a balance between O and N-acetylation and intermolecular bonds. (author)

Efficient Nonlocal M-Control and N-Target Controlled Unitary Gate Using Non-symmetric GHZ States

Science.gov (United States)

Chen, Li-Bing; Lu, Hong

2018-03-01

Efficient local implementation of a nonlocal M-control and N-target controlled unitary gate is considered. We first show that with the assistance of two non-symmetric qubit(1)-qutrit(N) Greenberger-Horne-Zeilinger (GHZ) states, a nonlocal 2-control and N-target controlled unitary gate can be constructed from 2 local two-qubit CNOT gates, 2 N local two-qutrit conditional SWAP gates, N local qutrit-qubit controlled unitary gates, and 2 N single-qutrit gates. At each target node, the two third levels of the two GHZ target qutrits are used to expose one and only one initial computational state to the local qutrit-qubit controlled unitary gate, instead of being used to hide certain states from the conditional dynamics. This scheme can be generalized straightforwardly to implement a higher-order nonlocal M-control and N-target controlled unitary gate by using M non-symmetric qubit(1)-qutrit(N) GHZ states as quantum channels. Neither the number of the additional levels of each GHZ target particle nor that of single-qutrit gates needs to increase with M. For certain realistic physical systems, the total gate time may be reduced compared with that required in previous schemes.

Composition of antioxidants and amino acids in Stevia leaf infusions.

Science.gov (United States)

Periche, Angela; Koutsidis, Georgios; Escriche, Isabel

2014-03-01

Stevia, a non-caloric natural sweetener with beneficial properties and considerable antioxidants and amino acids, is increasingly consumed as an infusion. This work evaluates the influence of the conditions (temperature: 50, 70 or 90 °C and time: 1, 5, 20 or 40 min) applied to obtain Stevia infusions, on antioxidants (total phenols, flavonoids and antioxidant activity) and amino acids. The total concentration of the eleven amino acids found was 11.70 mg/g in dried leaves and from 6.84 to 9.11 mg/g per gram of Stevia in infusions. However, infusions showed higher levels of certain amino acids (alanine, asparagine, leucine and proline), and greater values of the three antioxidant parameters in comparison with dry leaves. Temperature had more influence (minimum values at 50 °C and maximum at 90 °C) than time in the case of antioxidants. At 90 °C there were no important increases in the extraction of antioxidant compounds after 5 min; each gram of Stevia had 117 mg trolox (total antioxidant activity), 90 mg gallic acid (total phenols) and 56 mg catechin equivalents (flavonoids). Varying the temperature and time conditions no notable differences were observed in the concentrations of the majority of amino acids. However, the infusion treatment at 90 °C for 5 min was the best, as it gave the highest yield of 8 of the 11 amino acids. Therefore, with respect to the compounds analyzed in this study, the best way to obtain Stevia leaf infusions is the same as the domestic process, almost boiling water for a short time.

Transglycosylation reactions, a main mechanism of phenolics incorporation in coffee melanoidins: Inhibition by Maillard reaction.

Science.gov (United States)

Moreira, Ana S P; Nunes, Fernando M; Simões, Cristiana; Maciel, Elisabete; Domingues, Pedro; Domingues, M Rosário M; Coimbra, Manuel A

2017-07-15

Under roasting conditions, polysaccharides depolymerize and also are able to polymerize, forming new polymers through non-enzymatic transglycosylation reactions (TGRs). TGRs can also occur between carbohydrates and aglycones, such as the phenolic compounds present in daily consumed foods like coffee. In this study, glycosidically-linked phenolic compounds were quantified in coffee melanoidins, the polymeric nitrogenous brown-colored compounds formed during roasting, defined as end-products of Maillard reaction. One third of the phenolics present were in glycosidically-linked form. In addition, the roasting of solid-state mixtures mimicking coffee beans composition allowed the conclusion that proteins play a regulatory role in TGRs extension and, consequently, modulate melanoidins composition. Overall, the results obtained showed that TGRs are a main mechanism of phenolics incorporation in melanoidins and are inhibited by amino groups through Maillard reaction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of phenolic compounds on rumen microbial activity

International Nuclear Information System (INIS)

Vitti, D.M.S.S.; Abdalla, A.L.; Silva Filho, J.C.

1985-01-01

An 'in vitro' experiment is carried out to examine the effect of tannic acid on rumen microbial activity, due to the toxicity of phenolic acids on many microrganisms. Rumen content is incubated with sodium bicarbonate, glucose and different quantities of tannic acid. 1 μCi of 32 p-labelled phosphate is added and after 6 hours the incorporated activity is measured. (M.A.C.) [pt

Phenolic aminocarboxylic acids as gallium-binding radiopharmaceuticals

International Nuclear Information System (INIS)

Hunt, F.C.

1984-01-01

The phenolic aminocarboxylic acids ethylenediamine di [o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis [2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) form gallium complexes having high stability constants which enable them to resist exchange of gallium with plasma transferrin. 67 Ga complexes were synthesized with these ligands, placing substituent groups in the phenolic ring to direct excretion via the renal or hepatobiliary route. The amount of 67 Ga-Br-EDDHA excreted via the hepatobiliary route was comparable with that of some of the sup(99m)Tc agents. Excretion of 67 Ga-Br-HBED was similar but with delayed transit from the liver. 67 Ga COOH-EDDHA was excreted exclusively via the renal route. These findings provide a basis for developing new 67 Ga or 68 Ga radiopharmaceuticals, the latter for use in positron emission tomography, using these phenolic aminocarboxylates. (orig.) [de

Phenolic aminocarboxylic acids as gallium-binding radiopharmaceuticals.

Science.gov (United States)

Hunt, F C

1984-06-01

The phenolic aminocarboxylic acids ethylenediamine di [o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis [2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) form gallium complexes having high stability constants which enable them to resist exchange of gallium with plasma transferrin. 67Ga complexes were synthesized with these ligands, placing substituent groups in the phenolic ring to direct excretion via the renal or hepatobiliary route. The amount of 67Ga-Br-EDDHA excreted via the hepatobiliary route was comparable with that of some of the 99mTc agents. Excretion of 67Ga-Br-HBED was similar but with delayed transit from the liver. 67Ga COOH-EDDHA was excreted exclusively via the renal route. These findings provide a basis for developing new 67Ga or 68Ga radiopharmaceuticals, the latter for use in positron emission tomography, using these phenolic aminocarboxylates.

Synthetic, XRD, non-covalent interactions and solvent dependent nonlinear optical studies of Sulfadiazine-Ortho-Vanillin Schiff base: (E)-4-((2-hydroxy-3-methoxy- benzylidene) amino)-N-(pyrimidin-2-yl)benzene-sulfonamide

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Shahid, Muhammad; Salim, Muhammad; Khalid, Muhammad; Tahir, Muhammad Nawaz; Khan, Muhammad Usman; Braga, Ataualpa Albert Carmo

2018-06-01

In this study, Sulfadiazine-Ortho-Vanillin Schiff base namely (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS) was synthesized. Chemical characterization and computational studies using different techniques like XRD, FT-IR, UV-Vis, NBO, FMO, and MEP have been employed. Density functional theory (DFT) calculations have been performed at M06-2X/6-311 + G(d,p) level of theory to obtain optimized geometry and vibrational wave numbers for (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS). The DFT optimized geometry supports the experimental XRD parameters. Frontier molecular orbital (FMO) energies and molecular electrostatic potential (MEP) surfaces have been executed at M06-2X/6-311 + G(d,p) level of theory. NBO analysis has been carried out at M06-2X/6-311 + G(d,p) level which not only discovered the hyper conjugative interactions and stability in title molecule but also reconfirmed the existence of Nsbnd H⋯N hydrogen bonds between the dimer. The findings of small EHOMO-ELUMO gap shows less hardness and larger softness values which suggested the bioactiveness of the title molecule. Finally, the effect of solvent on nonlinear optical (NLO) properties has been executed using M06-2X level of theory and 6-311 + G (d,p) basis set. The solvent polarity enhanced the NLO response from 3.62 × 10-30 esu to 4.66 × 10-30 esu indicating the considerable NLO character hence in general may have potential applications in the development of non-linear optical materials.

INVESTIGACIÓN CUALITATIVA COMO JAZZ. Variaciones prospectivas de una analogía

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Carlos Iván García Suárez

2003-01-01

Full Text Available Este artículo pretende contribuir a la comprensión de los desafíos futuros de la investigación cualitativa, a partir del análisis de algunas transiciones significativas que se evidencian hoy en dicho campo. Lo hace en cuatro movimientos: pluralidad, diálogo, rigor y expresividad, como ejes de una analogía entre la investigación cualitativa y el jazz, que combina escritura personal e intertextualidad. Se recomienda escuchar la discografía mínima indicada al final.

Preventive effects of fructose and N-acetyl-L-cysteine against cytotoxicity induced by the psychoactive compounds N-methyl-5-(2-aminopropyl)benzofuran and 3,4-methylenedioxy-N-methamphetamine in isolated rat hepatocytes.

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Nakagawa, Yoshio; Suzuki, Toshinari; Inomata, Akiko

2018-02-01

Psychoactive compounds, N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB) and 3,4-methylenedioxy-N-methamphetamine (MDMA), are known to be hepatotoxic in humans and/or experimental animals. As previous studies suggested that these compounds elicited cytotoxicity via mitochondrial dysfunction and/or oxidative stress in rat hepatocytes, the protective effects of fructose and N-acetyl-l-cysteine (NAC) on 5-MAPB- and MDMA-induced toxicity were studied in rat hepatocytes. These drugs caused not only concentration-dependent (0-4 mm) and time-dependent (0-3 hours) cell death accompanied by the depletion of cellular levels of adenosine triphosphate (ATP) and glutathione (reduced form; GSH) but also an increase in the oxidized form of GSH. The toxic effects of 5-MAPB were greater than those of MDMA. Pretreatment of hepatocytes with either fructose at a concentration of 10 mm or NAC at a concentration of 2.5 mm prevented 5-MAPB-/MDMA-induced cytotoxicity. In addition, the exposure of hepatocytes to 5-MAPB/MDMA caused the loss of mitochondrial membrane potential, although the preventive effect of fructose was weaker than that of NAC. These results suggest that: (1) 5-MAPB-/MDMA-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were ameliorated, at least in part, by the addition of fructose; and (3) GSH loss via oxidative stress was prevented by NAC. Taken collectively, these results indicate that the onset of toxic effects caused by 5-MAPB/MDMA may be partially attributable to cellular energy stress as well as oxidative stress. Copyright © 2017 John Wiley & Sons, Ltd.

Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid

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Nye, Jonathon A., E-mail: jnye@emory.edu; Jarkas, Nashwa; Schuster, David M.; Savir-Baruch, Bital; Voll, Ronald J.; Camp, Vernon M.; Goodman, Mark M.

2011-10-15

Introduction: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[{sup 18}F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[{sup 18}F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans. Methods: A DU145 xenograft rodent model was used to measure anti-2-[{sup 18}F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[{sup 18}F]FACPC-1 toxicity was assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247{+-}61 MBq bolus injection of anti-2-[{sup 18}F]FACPC-1. Estimates of radiation dose from anti-2-[{sup 18}F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software. Results: High anti-2-[{sup 18}F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[{sup 18}F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq. Conclusion: Anti-2-[{sup 18}F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting

Acetyl L-Carnitine Modulating Irradiation Induced Cardio-Pulmonary Toxicity in Rats

International Nuclear Information System (INIS)

Gharib, O.A.

2006-01-01

In The Present study male adult Wister albino rats were irradiated at 4 Gy whole body gamma irradiation and Acetyl L-carnitine (ALC) was evaluated as a potential radio-protector under conditions that would model the oxidative stress syndrome. ALC protect the heart and lung from the depletion of SOD, GSHPx activities and GSH content followed radiation exposure. Protection from the increase of malonaldehyde (MDA) in heart and lung tissues as well as serum creatine phosphokinase (CPK), AST and LDH has been observed. These results imply that ALC can act as a radio-protector against many aspects of oxidative damage. ALC is an ester of the tri methylated amino acid L-carnitine, and is synthesized endogenously in the human brain, liver and kidney by the enzyme ALC transferase or obtained from dietary sources (Goa and Brogden, 1987). L carnitine and short chain derivatives are essential cofactors for mitochondrial transport and oxidation of long chain fatty acid and act also as scavengers of oxygen free radicals in mammalian tissue (Izgut-Uysal et al., 2001). The transport of ALC and PLC occurs more easily than L-carnitine through the lipid component of the intestinal barrier suggesting possible better oral bioavailability of the esters than L-carnitine (Marciniani et al., 1991). ALC has antioxidant activity towards oxidative stress via an inhibition of the increase in lipid hydro peroxidation (Yasui et al., 2002). ALC significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma (Marciniani et al., 1991) and has also shown neuro-protective effect in rats (Bigini et al., 2002)

Children's Ability to Recognise Toxic and Non-Toxic Fruits

Science.gov (United States)

Fancovicova, Jana; Prokop, Pavol

2011-01-01

Children's ability to identify common plants is a necessary prerequisite for learning botany. However, recent work has shown that children lack positive attitudes toward plants and are unable to identify them. We examined children's (aged 10-17) ability to discriminate between common toxic and non-toxic plants and their mature fruits presented in…

Amino acid metabolism of Lemna minor L

International Nuclear Information System (INIS)

Rhodes, D.; Rich, P.J.; Brunk, D.G.

1989-01-01

A serious limitation to the use of N(O,S)-heptafluorobutyryl isobutyl amino acid derivatives in the analysis of 15 N-labeling kinetics of amino acids in plant tissues, is that the amides glutamine and asparagine undergo acid hydrolysis to glutamate and aspartate, respectively, during derivatization. This led us to consider an alternative procedure for derivatization of glutamine and asparagine with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in pyridine. Gas chromatography-mass spectrometry yielded fragment ions (M-57) of mass 417 and 431 for the [ 14 N]asparagine and [ 14 N]glutamine derivatives, respectively, suitable for monitoring unlabeled, single- 15 N- and double- 15 N-labeled amide species from the ion clusters at mass to charge ratio (m/z) 415 to 423 for asparagine, and m/z 429 to 437 for glutamine. From separate analyses of the specific isotope abundance of the amino-N groups of asparagine and glutamine as their N-heptafluorobutyryl isobutyl derivatives, the specific amide-[ 15 N] abundance of these amino acids was determined

Amino acid sequence and biological characterization of BlatPLA₂, a non-toxic acidic phospholipase A₂ from the venom of the arboreal snake Bothriechis lateralis from Costa Rica.

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Van der Laat, Marco; Fernández, Julián; Durban, Jordi; Villalobos, Eva; Camacho, Erika; Calvete, Juan J; Lomonte, Bruno

2013-10-01

Bothriechis is considered a monophyletic, basal genus of arboreal Neotropical pitvipers distributed across Middle America. The four species found in Costa Rica (B. lateralis, B. schlegeli, B. nigroviridis, B. supraciliaris) differ in their venom proteomic profiles, suggesting that different Bothriechis taxa have evolved diverse trophic strategies. In this study, we isolated a phospholipase A₂ (PLA₂) from B. lateralis venom, aiming at increasing our knowledge on the structural and functional characteristics of group II acidic PLA₂s, whose toxic actions are generally more restricted than those displayed by basic PLA₂s. The new acidic enzyme, BlatPLA₂, occurs as a monomer of 13,917 Da, in contrast to many basic group II PLA₂s which associate into dimers and often display myotoxicity and/or neurotoxicity. Its amino acid sequence of 122 residues predicts an isoelectric point of 4.7, and displays significant differences with previously characterized acidic PLA₂s, with which it shows a maximum sequence identity of 78%. BlatPLA₂ is catalytically active but appears to be devoid of major toxic activities, lacking intravenous or intracerebroventricular lethality, myotoxicity, in vitro anticoagulant activity, and platelet aggregation or inhibition effects. Phylogenetic relationships with similar group II enzymes suggest that BlatPLA₂ may represent a basal sequence to other acidic PLA₂s. Due to the metabolic cost of venom protein synthesis, the presence of a relatively abundant (9%) but non-toxic component is somewhat puzzling. Nevertheless, we hypothesize that BlatPLA₂ could have a role in the pre-digestion of prey, possibly having retained characteristics of ancestral PLA₂s without evolving towards potent toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

A green non-acid-catalyzed process for direct N=N-C group formation: comprehensive study, modeling, and optimization.

Science.gov (United States)

Khakyzadeh, Vahid; Zolfigol, Mohammad Ali; Derakhshan-Panah, Fatemeh; Jafarian, Majid; Miri, Mir Vahid; Gilandoust, Maryam

2018-01-04

The aim of this work is to introduce, model, and optimize a new non-acid-catalyzed system for a direct N[Formula: see text]N-C bond formation. By reacting naphthols or phenol with anilines in the presence of the sodium nitrite as nitrosonium ([Formula: see text] source and triethylammonium acetate (TEAA), a N[Formula: see text]N-C group can be formed in non-acid media. Modeling and optimization of the reaction conditions were investigated by response surface method. Sodium nitrite, TEAA, and water were chosen as variables, and reaction yield was also monitored. Analysis of variance indicates that a second-order polynomial model with F value of 35.7, a P value of 0.0001, and regression coefficient of 0.93 is able to predict the response. Based on the model, the optimum process conditions were introduced as 2.2 mmol sodium nitrite, 2.2 mL of TEAA, and 0.5 mL [Formula: see text] at room temperature. A quadratic (second-order) polynomial model, by analysis of variance, was able to predict the response for a direct N=N-C group formation. Predicted response values were in good agreement with the experimental values. Electrochemistry studies were done to introduce new Michael acceptor moieties. Broad scope, high yields, short reaction time, and mild conditions are some advantages of the presented method.

Analysis of Protein Amino Acids in Tobacco Using Microwave Digestion of Plant Material

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Moldoveanu SC

2014-12-01

Full Text Available This paper describes a technique using microwave digestion and gas chromatography-mass spectrometry (GC-MS, which makes possible the analysis of protein amino acids in tobacco. The technique involves first the measurement of free amino acids, a hydrolysis using microwave digestion, and a measurement of total resulting amino acids. The content of protein amino acids is determined from the difference of total and free amino acids. The digestion is performed with aqueous 6 N HCl (with 1% phenol for two hours in a microwave at 120°C in sealed vials. The GC-MS analysis is performed after the amino acids are derivatized with N-methyl-N-(t-butyldimethylsilyltrifluoroacetamide (MTBSTFA. The technique provides reliable results with less than 10% relative standard deviation (RSD for most amino acids. Only the determination of very low level amino acids is affected by larger errors. The method provides results for free amino acids that are in very good agreement with those obtained by high performance liquid chromatography (HPLC, and also results for protein levels in tobacco in agreement with data previously reported in the literature. Results are given for several single grade tobaccos and for tobacco blends from four Kentucky reference cigarettes.

Investigating Hydrogen Bonding in Phenol Using Infrared Spectroscopy and Computational Chemistry

Science.gov (United States)

Fedor, Anna M.; Toda, Megan J.

2014-01-01

The hydrogen bonding of phenol can be used as an introductory model for biological systems because of its structural similarities to tyrosine, a para-substituted phenol that is an amino acid essential to the synthesis of proteins. Phenol is able to form hydrogen bonds readily in solution, which makes it a suitable model for biological…

Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

Science.gov (United States)

Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D

2013-01-01

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

Purification, crystallization and preliminary X-ray diffraction studies of a putative UDP-N-acetyl-d-mannosamine dehydrogenase from Pyrococcus horikoshii OT3

Energy Technology Data Exchange (ETDEWEB)

Lokanath, Neratur K.; Pampa, Kudigana J.; Kamiya, Toshimi; Kunishima, Naoki, E-mail: kunisima@spring8.or.jp [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan)

2007-05-01

A putative UDP-N-acetyl-d-mannosamine dehydrogenase from P. horikoshii OT3 has been crystallized in space group P2{sub 1}, with unit-cell parameters a = 80.28, b = 69.24, c = 83.10 Å, β = 114.4°. X-ray diffraction data have been collected to 1.80 Å resolution. A putative UDP-N-acetyl-d-mannosamine dehydrogenase from Pyrococcus horikoshii OT3, an essential enzyme for polysaccharide biosynthesis, has been overexpressed in Escherichia coli and purified. Crystals were obtained using the oil-microbatch method at 291 K. A native data set extending to 1.8 Å resolution has been collected and processed in space group P2{sub 1}. Assuming the presence of a dimer in the asymmetric unit, the V{sub M} value is calculated to be 2.3 Å{sup 3} Da{sup −1}, which is consistent with the result of a dynamic light-scattering experiment that shows a dimeric state of the protein in solution.

A kinetic and mechanistic study on the oxidation of l-methionine and N-acetyl l-methionine by cerium(IV in sulfuric acid medium

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T. Sumathi

2016-09-01

Full Text Available The kinetics of oxidation of l-methionine and N-acetyl l-methionine by Ce(IV in sulfuric acid–sulfate media in the range of 288.1–298.1 K has been investigated. The major oxidation products of methionine and N-acetyl l-methionine have been identified as methionine sulfoxide and N-acetyl methionine sulfoxide. The major oxidation products have been confirmed by qualitative analysis and boiling point. The reaction was first order with respect to l-methionine, N-acetyl l-methionine and Ce(IV. Increase in [H+], ionic strength and HSO4- did not affect the reaction rate. Under the experimental conditions, Ce4+ was the effective oxidizing species of cerium. Increase in dielectric constant of the medium decreased the reaction rate. Under nitrogen atmosphere, the reaction system can initiate polymerization of acrylonitrile, indicating the generation of free radicals. Activation parameters associated with the overall reaction have been calculated.

N-13 labeled amino acids: biodistribution, metabolism and dosimetric considerations

International Nuclear Information System (INIS)

Rosenspire, K.C.; Gelbard, A.S.

1986-01-01

With the growing interest in metabolic imaging and with the increasing number of cyclotron/PET facilities, more studies are being performed in animal and humans using short-lived positron-emitting radionuclides. Amino acids labeled either with N-13 or C-11 are one group of compounds being used to study in vivo regional organ (i.e., brain and heart) or tumor metabolism. Of the studies previously reported using C-11 or N-13 labeled amino acids (methionine, alanine, valine, glutamate, glutamine and tryptophan), imaging was restricted mainly to the organ or tissue of interest with little information obtained about the whole-bode distribution of the label. Such data are important for studying interorgan transport of amino acids and for determining accurate dosimetric measurements after intravenous injection of labeled amino acids. The goals of the authors study were to compare the distribution of several N-13 L-amino acids and N-13 ammonia in tumor-bearing mice and to determine the metabolic fate of the label in vivo. The following amino acids were enzymatically labeled using N-13 ammonia: glutamine, glutamate, methionine, α-aminobutyric acid, valine and leucine. 30 references, 2 figures, 14 tables

N-acetyl-aspartate (NAA) as a correlate of pharmacological treatment in psychiatric disorders: a systematic review.

Science.gov (United States)

Paslakis, Georgios; Träber, Frank; Roberz, Jens; Block, Wolfgang; Jessen, Frank

2014-10-01

The amino-acid N-acetyl-aspartate (NAA) is located in neurons and the concentration of NAA correlates with neuronal mitochondrial function. The signal of NAA, as measured with proton magnetic resonance spectroscopy (1H-MRS), is considered to reflect both, neuronal density and integrity of neuronal mitochondria. A reduction of the NAA concentrations has been found in several psychiatric disorders. Newer studies report reversal of decreased NAA concentration with treatment. The objective of this review is to summarize the literature on NAA changes in association with psychopharmacological treatment in psychiatric disorders (affective disorders, obsessive-compulsive disorder, schizophrenia and dementia). The majority of studies identified increased NAA concentrations in response to treatment, while a smaller number of studies did not find this effect. The NAA increase seems to be neither specific for a certain disorder nor for a specific intervention. This suggests that the reduction of NAA may represent an altered functional (metabolic) state of neurons common to different psychiatric disorders and the increase after treatment to indicate functional restoration as one general effect of interventions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Pyrrolizidine alkaloids in medicinal tea of Ageratum conyzoides

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Cristiane F. Bosi

2013-06-01

Full Text Available It is now widely-recognized that the view that herbal remedies have no adverse effects and/or toxicity is incorrect; some traditionally-used plants can present toxicity. The well-established popular use of Ageratum conyzoides has led to its inclusion in a category of medicinal crude drugs created by the Brazilian Health Surveillance Agency. Ageratum belongs to the Eupatorieae tribe, Asteraceae, and is described as containing toxic pyrrolizidine alkaloids. Aqueous extracts of Ageratum conyzoides L. harvested in Brazil (commercial, flowering and non-flowering samples were prepared according to the prescribed method and analyzed by HPLC-HRMS. The pyrrolizidine alkaloids lycopsamine, dihydrolycopsamine, and acetyl-lycopsamine and their N-oxides, were detected in the analyzed extracts, lycopsamine and its N-oxide being known hepatotoxins and tumorigens. Together with the pyrrolizidine alkaloids identified by HPLC-HRMS, thirteen phenolic compounds were identified, notably, methoxylated flavonoids and chromenes. Toxicological studies on A. conyzoides are necessary, as is monitoring of its clinical use. To date, there are no established safety guidelines on pyrrolizidine alkaloids-containing plants, and their use in Brazil.

Pyrrolizidine alkaloids in medicinal tea of Ageratum conyzoides

Directory of Open Access Journals (Sweden)

Cristiane F. Bosi

2013-03-01

Full Text Available It is now widely-recognized that the view that herbal remedies have no adverse effects and/or toxicity is incorrect; some traditionally-used plants can present toxicity. The well-established popular use of Ageratum conyzoides has led to its inclusion in a category of medicinal crude drugs created by the Brazilian Health Surveillance Agency. Ageratum belongs to the Eupatorieae tribe, Asteraceae, and is described as containing toxic pyrrolizidine alkaloids. Aqueous extracts of Ageratum conyzoides L. harvested in Brazil (commercial, flowering and non-flowering samples were prepared according to the prescribed method and analyzed by HPLC-HRMS. The pyrrolizidine alkaloids lycopsamine, dihydrolycopsamine, and acetyl-lycopsamine and their N-oxides, were detected in the analyzed extracts, lycopsamine and its N-oxide being known hepatotoxins and tumorigens. Together with the pyrrolizidine alkaloids identified by HPLC-HRMS, thirteen phenolic compounds were identified, notably, methoxylated flavonoids and chromenes. Toxicological studies on A. conyzoides are necessary, as is monitoring of its clinical use. To date, there are no established safety guidelines on pyrrolizidine alkaloids-containing plants, and their use in Brazil.

Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells

DEFF Research Database (Denmark)

Thit, Amalie; Selck, Henriette; Bjerregaard, Henning F.

2015-01-01

and levels of reduced glutathione (GSH) and eventually cell death. We show that ROS (Reactive Oxygen Species) generation plays a key role and occurs early in Poly toxicity as Poly-induced DNA damage and cell death could be mitigated by the antioxidant NAC (N-acetyl-cysteine). Here we propose a model...

Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

Science.gov (United States)

Sun, Man; Yang, Hui-Hui; Tian, Lei; Li, Jian-Qiang; Zhao, Wei-Guang

2015-12-15

The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9μM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew. Copyright © 2015 Elsevier Ltd. All rights reserved.

L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

Science.gov (United States)

Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

2017-03-01

L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective Effects of Acetylation on the Pathological Reactions of the Lens Crystallins with Homocysteine Thiolactone.

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Zeinab Moafian

Full Text Available Various post-translational lens crystallins modifications result in structural and functional insults, contributing to the development of lens opacity and cataract disorders. Lens crystallins are potential targets of homocysteinylation, particularly under hyperhomocysteinemia which has been indicated in various eye diseases. Since both homocysteinylation and acetylation primarily occur on protein free amino groups, we applied different spectroscopic methods and gel mobility shift analysis to examine the possible preventive role of acetylation against homocysteinylation. Lens crystallins were extensively acetylated in the presence of acetic anhydride and then subjected to homocysteinylation in the presence of homocysteine thiolactone (HCTL. Extensive acetylation of the lens crystallins results in partial structural alteration and enhancement of their stability, as well as improvement of α-crystallin chaperone-like activity. In addition, acetylation partially prevents HCTL-induced structural alteration and aggregation of lens crystallins. Also, acetylation protects against HCTL-induced loss of α-crystallin chaperone activity. Additionally, subsequent acetylation and homocysteinylation cause significant proteolytic degradation of crystallins. Therefore, further experimentation is required in order to judge effectively the preventative role of acetylation on the structural and functional insults induced by homocysteinylation of lens crystallins.

Phenolic aminocarboxylic acids as gallium-binding radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Hunt, F.C.

1984-06-01

The phenolic aminocarboxylic acids ethylenediamine di (o-hydroxyphenylacetic acid) (EDDHA) and N,N'-bis (2-hydroxybenzyl) ethylenediamine N,N'-diacetic acid (HBED) form gallium complexes having high stability constants which enable them to resist exchange of gallium with plasma transferrin. /sup 67/Ga complexes were synthesized with these ligands, placing substituent groups in the phenolic ring to direct excretion via the renal or hepatobiliary route. The amount of /sup 67/Ga-Br-EDDHA excreted via the hepatobiliary route was comparable with that of some of the sup(99m)Tc agents. Excretion of /sup 67/Ga-Br-HBED was similar but with delayed transit from the liver. /sup 67/Ga COOH-EDDHA was excreted exclusively via the renal route. These findings provide a basis for developing new /sup 67/Ga or /sup 68/Ga radiopharmaceuticals, the latter for use in positron emission tomography, using these phenolic aminocarboxylates.

Non-toxic invert analog glass compositions of high modulus

Science.gov (United States)

Bacon, J. F. (Inventor)

1974-01-01

Glass compositions having a Young's modulus of at least 15 million psi are described. They and a specific modulus of at least 110 million inches consist essentially of, in mols, 15 to 40% SiO2, 6 to 15% Li2O, 24 to 45% of at least two bivalent oxides selected from the group consisting of Ca, NzO, MgO and CuO; 13 to 39% of at least two trivalent oxides selected from the group consisting of Al2O3, Fe2O3, B2O3, La2O3, and Y2O3 and up to 15% of one or more tetravelent oxides selected from the group consisting of ZrO2, TiO2 and CeO2. The high modulus, low density glass compositions contain no toxic elements. The composition, glass density, Young's modulus, and specific modulus for 28 representative glasses are presented. The fiber modulus of five glasses are given.

Farmacogenética: importancia de la determinación del fenoticpo acetilador Pharmacogenitecs: importance of acetylating phenotype determination

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Alvaro Perez Arcila

1994-02-01

Full Text Available

El campo de la investigación relacionado con las respuestas de base hereditaria a las drogas se ha denominado farmacogenética. Se han descrito al menos 60 polimorfismos farmacogenéticos en la medicina clínica; muchos de ellos son responsables de las marcadas diferencias en la predisposición gen ética para

desarrollar toxicidad por drogas O cáncer. En este momento los polimorfismos de mayor atención son los de la debrisoquina-esparteína y de la N-acetilación por el gran número de fármacos de prescripción común y de aminas carcinogénicas que utilizan estas enzimas para su inactivación.

Research concerning hereditary basis of response to drugs is known as pharmacogenetics; at least 60 pharmacogenetic polymorphisms have been described in clinical medicine; many of them are responsible for marked differences in predisposition towards drug toxicity or cancer. The debrisoquine.esparteine and the N-acetylation polymorphisms are presently the most important, since they involve both many frequently prescribed drugs, and carcinogenic amines that use this enzyme for inactivation.

Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through increasing histone acetylation and activation of NF-kappaB.

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Hao Ying

Full Text Available Histone deacetylase (HDAC inhibitors present an exciting new approach to activate HIV production from latently infected cells to potentially enhance elimination of these cells and achieve a cure. M344, a novel HDAC inhibitor, shows robust activity in a variety of cancer cells and relatively low toxicity compared to trichostatin A (TSA. However, little is known about the effects and action mechanism of M344 in inducing HIV expression in latently infected cells.Using the Jurkat T cell model of HIV latency, we demonstrate that M344 effectively reactivates HIV-1 gene expression in latently infected cells. Moreover, M344-mediated activation of the latent HIV LTR can be strongly inhibited by a NF-κB inhibitor aspirin. We further show that M344 acts by increasing the acetylation of histone H3 and histone H4 at the nucleosome 1 (nuc-1 site of the HIV-1 long terminal repeat (LTR and by inducing NF-κB p65 nuclear translocation and direct RelA DNA binding at the nuc-1 region of the HIV-1 LTR. We also found that M344 synergized with prostratin to activate the HIV-1 LTR promoter in latently infected cells.These results suggest the potential of M344 in anti-latency therapies and an important role for histone modifications and NF-κB transcription factors in regulating HIV-1 LTR gene expression.

Toxic effect of Cr(VI) in presence of n-TiO2 and n-Al2O3 particles towards freshwater microalgae.

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Dalai, Swayamprava; Pakrashi, Sunandan; Bhuvaneshwari, M; Iswarya, V; Chandrasekaran, N; Mukherjee, Amitava

2014-01-01

The reactivity and toxicity of the soluble toxicants in the presence of the engineered nanomaterials is not well explored. In this study, the probable effects of TiO2 and Al2O3 nanoparticles (n-TiO2, n-Al2O3) on the toxicity of Cr(VI) were assessed with the dominant freshwater algae, Scenedesmus obliquus, in a low range of exposure concentrations (0.05, 0.5 and 1μg/mL). In the presence of 0.05μg/mL n-TiO2, the toxicity of Cr(VI) decreased considerably, which was presumably due to the Cr(VI) adsorption on the nanoparticle surface leading to its aggregation and precipitation. The elevated n-TiO2 concentrations (0.5 and 1μg/mL) did not significantly influence Cr(VI) bio-availability, and a dose dependent toxicity of Cr(VI) was observed. On the other hand, n-Al2O3 did not have any significant effect on the Cr(VI) toxicity. The microscopic observations presented additional information on the morphological changes of the algal cells in the presence of the binary toxicants. The generation of reactive oxygen species (ROS) suggested contribution of oxidative stress on toxicity and LDH release confirmed membrane permeability of algal cells upon stress. Copyright © 2013 Elsevier B.V. All rights reserved.

1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

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Atul Rawat

2016-01-01

Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

Development of Rare Bacterial Monosaccharide Analogs for Metabolic Glycan Labeling in Pathogenic Bacteria.

Science.gov (United States)

Clark, Emily L; Emmadi, Madhu; Krupp, Katharine L; Podilapu, Ananda R; Helble, Jennifer D; Kulkarni, Suvarn S; Dube, Danielle H

2016-12-16

Bacterial glycans contain rare, exclusively bacterial monosaccharides that are frequently linked to pathogenesis and essentially absent from human cells. Therefore, bacterial glycans are intriguing molecular targets. However, systematic discovery of bacterial glycoproteins is hampered by the presence of rare deoxy amino sugars, which are refractory to traditional glycan-binding reagents. Thus, the development of chemical tools that label bacterial glycans is a crucial step toward discovering and targeting these biomolecules. Here, we explore the extent to which metabolic glycan labeling facilitates the studying and targeting of glycoproteins in a range of pathogenic and symbiotic bacterial strains. We began with an azide-containing analog of the naturally abundant monosaccharide N-acetylglucosamine and discovered that it is not broadly incorporated into bacterial glycans, thus revealing a need for additional azidosugar substrates to broaden the utility of metabolic glycan labeling in bacteria. Therefore, we designed and synthesized analogs of the rare deoxy amino d-sugars N-acetylfucosamine, bacillosamine, and 2,4-diacetamido-2,4,6-trideoxygalactose and established that these analogs are differentially incorporated into glycan-containing structures in a range of pathogenic and symbiotic bacterial species. Further application of these analogs will refine our knowledge of the glycan repertoire in diverse bacteria and may find utility in treating a variety of infectious diseases with selectivity.

Density, viscosity, and N2O solubility of aqueous amino acid salt and amine amino acid salt solutions

International Nuclear Information System (INIS)

Aronu, Ugochukwu E.; Hartono, Ardi; Svendsen, Hallvard F.

2012-01-01

Highlights: ► Density of amino acid salt and amine amino acid salt. ► Viscosity of amino acid salt and amine amino acid salt. ► Henry’s law constant/N 2 O solubility of amino acid salt and amine amino acid salt. ► Schumpe model. Correlations for density, viscosity, and N 2 O solubility. - Abstract: Physicochemical properties of aqueous amino acid salt (AAS), potassium salt of sarcosine (KSAR) and aqueous amine amino acid salt (AAAS), 3-(methylamino)propylamine/sarcosine (SARMAPA) have been studied. Densities of KSAR were measured for sarcosine mole fraction 0.02 to 0.25 for temperature range 298.15 K to 353.15 K, the viscosities were measured for 0.02 to 0.10 mole fraction sarcosine (293.15 K to 343.15 K) while the N 2 O solubilities were measured from 0.02 to 0.10 mole fraction sarcosine solutions (298.15 K to 363.15 K). Densities of SARMAPA were measured for sarcosine mole fraction 0.02 to 0.23 for temperature range (298.15 K to 353.15 K), viscosities were measured for 0.02 to 0.16 mole fraction sarcosine (293.15 K to 343.15 K) while the N 2 O solubilities were measured from 0.02 to 0.16 mole fraction sarcosine solutions (298.15 K to 343.15 K). Experimental results were correlated well with empirical correlations and N 2 O solubility results for KSAR were predicted adequately by a Schumpe model. The solubilities of N 2 O in AAS and AAAS are significantly lower than values for amines. The solubilities vary as: amine > AAAS > AAS.

Antileishmanial, toxicity, and phytochemical evaluation of medicinal plants collected from Pakistan.

Science.gov (United States)

Shah, Naseer Ali; Khan, Muhammad Rashid; Nadhman, Akhtar

2014-01-01

Leishmaniasis is an important parasitic problem and is in focus for development of new drugs all over the world. Objective of the present study was to evaluate phytochemical, toxicity, and antileishmanial potential of Jurinea dolomiaea, Asparagus gracilis, Sida cordata, and Stellaria media collected from different areas of Pakistan. Dry powder of plants was extracted with crude methanol and fractionated with n-hexane, chloroform, ethyl acetate, n-butanol, and water solvents in escalating polarity order. Qualitative phytochemical analysis of different class of compounds, that is, alkaloids, saponins, terpenoids, anthraquinones, cardiac glycosides, coumarins, phlobatannins, flavonoids, phenolics, and tannins, was tested. Its appearance was observed varying with polarity of solvent used for fractionation. Antileishmanial activity was performed against Leishmania tropica KWH23 promastigote. Potent antileishmanial activity was observed for J. dolomiaea methanol extract (IC50 = 10.9 ± 1.1 μ g/mL) in comparison to other plant extracts. However, J. dolomiaea "ethyl acetate fraction" was more active (IC50 = 5.3 ± 0.2 μ g/mL) against Leishmania tropica KWH23 among all plant fractions as well as standard Glucantime drug (6.0 ± 0.1 μ g/mL). All the plants extract and its derived fraction exhibited toxicity in safety range (LC50 > 100) in brine shrimp toxicity evaluation assay.

A three-enzyme-system to degrade curcumin to natural vanillin.

Science.gov (United States)

Esparan, Vida; Krings, Ulrich; Struch, Marlene; Berger, Ralf G

2015-04-14

The symmetrical structure of curcumin includes two 4-hydroxy-3-methoxyphenyl substructures. Laccase catalyzed formation of a phenol radical, radical migration and oxygen insertion at the benzylic positions can result in the formation of vanillin. As vanillin itself is a preferred phenolic substrate of laccases, the formation of vanillin oligomers and polymers is inevitable, once vanillin becomes liberated. To decelerate the oligomerization, one of the phenolic hydroxyl groups was protected via acetylation. Monoacetyl curcumin with an approximate molar yield of 49% was the major acetylation product, when a lipase from Candida antarctica (CAL) was used. In the second step, monoacetyl curcumin was incubated with purified laccases of various basidiomycete fungi in a biphasic system (diethyl ether/aqueous buffer). A laccase from Funalia trogii (LccFtr) resulted in a high conversion (46% molar yield of curcumin monoacetate) to vanillin acetate. The non-protected vanillin moiety reacted to a mixture of higher molecular products. In the third step, the protecting group was removed from vanillin acetate using a feruloyl esterase from Pleurotus eryngii (PeFaeA) (68% molar yield). Alignment of the amino acid sequences indicated that high potential laccases performed better in this mediator and cofactor-free reaction.

Induction of phenolic metabolites and physiological changes in chamomile plants in relation to nitrogen nutrition.

Science.gov (United States)

Kováčik, Jozef; Klejdus, Bořivoj

2014-01-01

Alternative tools, such as the manipulation of mineral nutrition, may affect secondary metabolite production and thus the nutritional value of food/medicinal plants. We studied the impact of nitrogen (N) nutrition (nitrate/NO3(-) or ammonium/NH4(+) nitrogen) and subsequent nitrogen deficit on phenolic metabolites and physiology in Matricaria chamomilla plants. NH4(+)-fed plants revealed a strong induction of selected phenolic metabolites but, at the same time, growth, Fv/Fm, tissue water content and soluble protein depletion occurred in comparison with NO3(-)-fed ones. On the other hand, NO3(-)-deficient plants also revealed an increase in phenolic metabolites but growth depression was not observed after the given exposure period. Free amino acids were more accumulated in NH4(+)-fed shoots (strong increase in arginine and proline mainly), while the pattern of roots' accumulation was independent of N form. Among phenolic acids, NH4(+) strongly elevated mainly the accumulation of chlorogenic acid. Within flavonoids, flavonols decreased while flavones strongly increased in response to N deficiency. Coumarin-related metabolites revealed a similar increase in herniarin glucosidic precursor in response to N deficiency, while herniarin was more accumulated in NO3(-)- and umbelliferone in NH4(+)-cultured plants. These data indicate a negative impact of NH4(+) as the only source of N on physiology, but also a higher stimulation of some valuable phenols. Nitrogen-induced changes in comparison with other food/crop plants are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, A Review of Effectiveness in Reducing HIV Progression

NARCIS (Netherlands)

R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); G.K. Reid (Gregor)

2010-01-01

textabstractLow serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical

Micronutrients, N-acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression

NARCIS (Netherlands)

R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); G. Reid (Gregor)

2010-01-01

textabstractLow serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical

Formation constants of Sm(III), Dy(III), Gd(III), Pr(III) and Nd(III) complexes of tridentate schiff base, 2-[(1H-benzimidazol-2-yl-methylene) amino] phenol

International Nuclear Information System (INIS)

Omprakash, K.L.; Chandra Pal, A.V.; Reddy, M.L.N.

1982-01-01

A new tridentate schiff base, 2- (1H-benzimidazol-2-yl-methylene)amino phenol derived from benzimididazole-2-carbo-xaldehyde and 2-aminophenol has been synthesised and characterised by spectral and analytical data. Proton-ligand formation constants of the schiff base and metal-ligand formation constants of its complexes with Sm(III), Dy(III), Gd(III), Nd(III) and Pr(III) have been determined potentiometrically in 50% (v/v) aqueous dioxane at an ionic strength of 0.1M (NaClO 4 ) and at 25deg C using the Irving-Rossotti titration technique. The order of stability constants (logβ 2 ) is found to be Sm(III)>Dy(III)>Gd(III)>Pr(III)>Nd(III). (author)

Formation constants of Sm(III), Dy(III), Gd(III), Pr(III) and Nd(III) complexes of tridentate schiff base, 2-((1H-benzimidazol-2-yl-methylene) amino) phenol

Energy Technology Data Exchange (ETDEWEB)

Omprakash, K L; Chandra Pal, A V; Reddy, M L.N. [Osmania Univ., Hyderabad (India). Dept. of Chemistry

1982-03-01

A new tridentate schiff base, 2- (1H-benzimidazol-2-yl-methylene)amino phenol derived from benzimididazole-2-carbo-xaldehyde and 2-aminophenol has been synthesised and characterised by spectral and analytical data. Proton-ligand formation constants of the schiff base and metal-ligand formation constants of its complexes with Sm(III), Dy(III), Gd(III), Nd(III) and Pr(III) have been determined potentiometrically in 50% (v/v) aqueous dioxane at an ionic strength of 0.1M (NaClO/sub 4/) and at 25deg C using the Irving-Rossotti titration technique. The order of stability constants (log..beta../sub 2/) is found to be Sm(III)>Dy(III)>Gd(III)>Pr(III)>Nd(III).

Effects of surface chemical properties of activated carbon modified by amino-fluorination for electric double-layer capacitor.

Science.gov (United States)

Jung, Min-Jung; Jeong, Euigyung; Cho, Seho; Yeo, Sang Young; Lee, Young-Seak

2012-09-01

The surface of phenol-based activated carbon (AC) was seriatim amino-fluorinated with solution of ammonium hydroxide and hydrofluoric acid in varying ratio to fabricate electrode materials for use in an electric double-layer capacitor (EDLC). The specific capacitance of the amino-fluorinated AC-based EDLC was measured in a 1 M H(2)SO(4) electrolyte, in which it was observed that the specific capacitances increased from 215 to 389 Fg(-1) and 119 and 250 Fg(-1) with the current densities of 0.1 and 1.0 Ag(-1), respectively, in comparison with those of an untreated AC-based EDLC when the amino-fluorination was optimized via seriatim mixed solution of 7.43 mol L(-1) ammonium hydroxide and 2.06 mol L(-1) hydrofluoric acid. This enhancement of capacitance was attributed to the synergistic effects of an increased electrochemical activity due to the formation of surface N- and F-functional groups and increased, specific surface area, and mesopore volumes, all of which resulted from the amino-fluorination of the electrode material. Copyright © 2012 Elsevier Inc. All rights reserved.

Scope and limitations of the Heck-Matsuda-coupling of phenol diazonium salts and styrenes: a protecting-group economic synthesis of phenolic stilbenes.

Science.gov (United States)

Schmidt, Bernd; Elizarov, Nelli; Berger, René; Hölter, Frank

2013-06-14

4-Phenol diazonium salts undergo Pd-catalyzed Heck reactions with various styrenes to 4'-hydroxy stilbenes. In almost all cases higher yields and fewer side products were observed, compared to the analogous 4-methoxy benzene diazonium salts. In contrast, the reaction fails completely with 2- and 3-phenol diazonium salts. For these substitution patterns the methoxy-substituted derivatives are superior.

Behavior of 15N-labelled amino acids in germinated corn

International Nuclear Information System (INIS)

Samukawa, Kisaburo; Yamaguchi, Masuro

1979-01-01

By investigating the rise and fall of 15 N-labelled amino acids in germinated corns, the behavior of amino radicals in free amino acids, the influence of the hydrolysis products of stored proteins on free amino acids and the change from heterotrophy to autotrophy of seeds were clarified. The amount of amino acid production depending on external nitrogen was very small in the early period of germination. 15 N incorporation into proline was not observed in the early period of germination, which suggested that the proline may be nitrogen-storing source. Most of the amino-state nitrogen of asparagine accumulated at the time of germination was internal nitrogen, and this fact suggested that aspartic acid serve as the acceptor of ammonia produced in the early stage of germination. 15 N content increased significantly on 9 th day after germination, and decreased on 12 th day. These facts prove that there are always active decomposition and production of protein in plant body. (Kobatake, H.)

Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2).

Science.gov (United States)

Edwards, Noel; Anderson, Catriona M H; Gatfield, Kelly M; Jevons, Mark P; Ganapathy, Vadivel; Thwaites, David T

2011-01-01

The H(+)-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2 in amino acid reabsorption in the renal proximal tubule is demonstrated by mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and glycine uria) in humans. A number of proline, GABA and tryptophan derivatives were examined to determine if they function either as transported substrates or non-transported inhibitors of PAT2. The compounds were investigated following heterologous expression of rat PAT2 in Xenopus laevis oocytes. PAT2 function was characterised by: radiotracer uptake and competition (cis-inhibition) studies; radiotracer efflux and trans-stimulation; and measurement of substrate-induced positive inward current by two-electrode voltage-clamp. In general, the proline derivatives appeared to be transported substrates and the relative ability to induce current flow was closely related to the inhibitory effects on PAT2-mediated l-[(3)H]proline uptake. In contrast, certain heterocyclic GABA derivatives (e.g. l-pipecolic acid) were translocated only slowly. Finally, the tryptophan derivatives inhibited PAT2 function but did not undergo transport. l-Proline uptake was inhibited by 5-hydroxy-l-tryptophan (IC(50) 1.6±0.4mM), α-methyl-d,l-tryptophan (3.5±1.5mM), l-tryptophan, 1-methyl-l-tryptophan and indole-3-propionic acid. Although neither 5-hydroxy-l-tryptophan nor α-methyl-d,l-tryptophan were able to elicit inward current in PAT2-expressing oocytes both reduced the current evoked by l-proline. 5-Hydroxy-l-tryptophan and α-methyl-d,l-tryptophan were unable to trans-stimulate l-proline efflux from PAT2-expressing oocytes, confirming that the two compounds act as non-transported blockers of PAT2. These two tryptophan derivatives should prove valuable experimental tools in future investigations of the physiological roles of PAT2. Copyright © 2010 Elsevier B.V. All rights

Complexation of Phenol and Thiophenol by Amine N-Oxides: Isothermal Titration Caloritmetry and ab Initio Calculations

NARCIS (Netherlands)

Cuypers, R.; Sukumaran, M.; Marcelis, A.T.M.; Sudhölter, E.J.R.; Zuilhof, H.

2010-01-01

To develop a new solvent-impregnated resin (SIR) system for removal of phenols from water the complex formation of dimethyldodecylamine. N-oxide (DMDAO), trioctylamine N-oxide (TOAO), and tris(2-ethylhexyl)amine N-oxide (TEHAO) with phenol (PhOH) and thiophenol (PhSH) is studied To this end we use