Abstract  Alcohols are widely used as industrial solvents. In spite of the fact that ethanol is a human teratogen, there has not been systematic investigation of the potential teratogenic effects of other alcohols, particularly using the inhalation route of exposure, as would be appropriate in assessing occupational and environmental types of experience. As part of a large teratological examination of industrial alcohols, methanol and ethanol were administered by inhalation to groups of approximately 15 pregnant Sprague-Dawley rats. Methanol was administered at 20,000 ppm (20ME), 10,000 ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day on Days 1-19 of gestation (Days 7-15 for 20ME). Ethanol was administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000 ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1-19 of gestation. Dams were sacrificed on Day 20 (sperm = Day 0). One-half of the fetuses were examined using the Wilson technique for visceral defects, and the other half were examined for skeletal defects. The highest concentration of methanol (20ME) produced slight maternal toxicity and a high incidence of congenital malformations (p less than 0.001), predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were seen in the 10ME group, but the incidence was not significantly different from controls. No adverse effects were noted in the 5ME group. Dams in the 20ET group were narcotized by the end of exposure, and maternal weight gain and feed intake were decreased during the first week of exposure. The 16ET dams had slightly depressed weight gain (p less than 0.01) during the first week of exposure, but there were no significant effects on feed consumption. There was no definite increase in malformations at any level of ethanol, although the incidence in the 20ET group was of borderline significance.

Abstract  The characteristics of chlorate (ClO(3)(-)) and perchlorate (ClO(4)(-)) formation were studied during the electrolysis of water containing chloride ions (Cl(-)). The experiments were performed using an undivided Pt/Ti plate electrode under different pH conditions (pH 3.6, 5.5, 7.2, 8.0 and 9.0). ClO(3)(-) and ClO(4)(-) were formed during electrolysis in proportion to the Cl(-) concentration. The generation rates of ClO(3)(-) and ClO(4)(-) under acidic conditions (pH 3.6 and 5.5) were lower than in basic pH conditions (pH 7.2, 8.0 and 9.0). However, the pH of the solution did not influence the conversion of ClO(3)(-) to ClO(4)(-). The effects of intermediately formed oxidants on the production of ClO(3)(-) and ClO(4)(-) were observed using sodium thiosulfate (Na(2)S(2)O(3)) as the active chlorine scavenger and tertiary butyl alcohol (t-BuOH) as the hydroxyl radical (OH) scavenger. The results revealed that electrolysis reactions that involved active chlorine contributed dominantly to ClO(3)(-) production. The direct oxidation reaction rate of Cl(-) to ClO(3)(-) was 13%. The OH species that were intermediately formed during electrolysis were also found to significantly affect ClO(3)(-) and ClO(4)(-) production. The key formation pathways of ClO(3)(-) and ClO(4)(-) were studied using kinetic model development.

Abstract  Cyclotrimethylenetrinitramine (RDX) has been used extensively as an explosive. Prior to this study no data were available on the metabolism of RDX in animals. Metabolism of 14C-RDX was studied in male and female miniature pigs after a one-time gavage with 41 to 44 mg/kg, (0.8 to 0.9 mCi/animal) in an aqueous suspension of 0.1% carboxymethyl cellulose. Metabolic profiles and identification of 14C-RDX-derived radioactivity in plasma, liver and urine were performed utilizing HPLC radio-scanning and LC/MS/MS analysis. Analytical standards were available for all proposed metabolites. Two HPLC columns with differing elution profiles were used for separation, quantification and tentative identification. Identifications were confirmed using LC/MS/MS. Two metabolites were isolated and identified as 4-nitro-2, 4-diazabutanal and a novel metabolite, 4-nitro- 2-4 diaza-butanamide. Analysis also revealed trace levels of 1-nitroso-3,5-dinitro-1,3,5-triazacyclohexane (MNX), 1,3-dintroso-5-nitro-1,3,5-triazacyclohexane (DNX) and 1,3,5-trinitroso- 1,3,5-triazacyclohexane (TNX) in plasma and showed trace levels of MNX and DNX in urine. No metabolites were detected in the liver samples. Thus RDX was metabolized primarily by a method that accomplished both denitration and oxidative cleavage of the ring structure of this compound to form butanal and butanamide metabolites.

Abstract  This experimental study deals with the colloidal stability of sterically functionalized magnetite nanoparticles in a low dielectric constant organic solvent with different concentrations of technical grade polymers. Those dispersions are the starting point of a solution and spray drying process chain to synthesize highly filled nanocomposite materials with nanoparticle volume concentrations exceeding 10%. We introduce a thermo gravimetric method together with light extinction and dynamic light scattering measurements to gain quantitative information on the concentration of primary particles and the mechanism of destabilization or stabilization by polymer addition. Poly(vinyl butyral) is found to stabilize the dispersion considerably caused by stronger interactions with the fatty acid coated magnetite particles quantified by means of adsorption measurements. Both poly(methyl methacrylate) as well as two grades of poly(bisphenol A carbonate) are found to destabilize the dispersion due to depletion flocculation over the entire concentration range investigated However there is a significant quantity of a stable fraction of primary nanoparticles in the supernatant after depletion flocculation occurred. This fraction of primary particles is increasing with decreasing polymer concentration. We furthermore point out important concerns and limitations for the composition of and concentrations in such complex colloidal systems for use in industrially relevant processes.

Abstract  Tertiary butyl alcohol (TBA) was administered to groups of 15 female B6C3F1 mice in drinking water at concentrations of 0, 2.0 or 20 mg TBA ml(-1), for 14 days, for assessment of gross and histological changes in the liver and thyroid, thyroid hormones (T3, T4, and TSH), total hepatic cytochrome P450 (Cyp) content, specific Cyp activities and quantitative PCR analysis of specific Cyp enzymes (Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11), sulfuryltransferases (ST1a1, ST2a2, and STn) and glucuronyltransferases (UGT1a1, UGT2b1, and UGT2b5). Phenobarbital (PB) was administered to a positive control group by oral gavage at a daily dose of 80 mg kg(-1). TBA caused, on day 14, a reduction in circulating T3 (12-15% decrease) and a dose-dependent reduction in T4 (13-22% decrease), with no evidence of thyroid pathology. Two of five livers examined in the 20 mg TBA ml(-1) dose group showed mild, diffuse centrilobular hypertrophy. On day 14, Cyp 7-benzoxyresorufin-O-debenzylase activity was significantly induced 12-fold by TBA at 20 mg ml(-1), and 1.8-fold at the 2.0 mg TBA ml(-1) concentration. Cyp 7-pentoxyresorufin-O-dealkylase activity was slightly induced (2.1-fold) by 20 mg TBA ml(-1) on day 14. Quantitative PCR analysis of gene transcripts showed a significant induction of Cyp2b10 and ST1a1 with both TBA concentrations, and a slight induction of Cyp2b9 at 20 mg TBA ml(-1) only. PB induced all phase I and phase II gene transcripts except for Cyp1a1 and Cyp2b9. These findings suggest that TBA, at and below doses used in chronic studies, is an inducer of phase I and phase II liver enzymes, with resulting decreases in circulating thyroid hormones in B6C3F1 mice.

Abstract  Abstract: In this paper, we evaluate the efficiency of UV/H2O2 process to remove methyl tert-butyl ether (MtBE) and tertiary butyl alcohol (tBA) from a drinking water source. Kinetic models were used to evaluate the removal efficiency of the UV/H2O2 technologies with different pretreatment options and light sources. Two commercial UV light sources, i.e. low pressure, high intensity lamps and medium pressure, high intensity lamps, were evaluated. The following pretreatment alternatives were evaluated: (1) ion exchange softening with seawater regeneration (NaIX); (2) Pellet Softening; (3) weak acid ion exchange (WAIX); and (4) high pH lime softening followed by reverse osmosis (RO). The presence or absence of a dealkalization step prior to the UV/H2O2 Advanced Oxidation Process (AOP) was also evaluated for each pretreatment possibility. Pretreatment has a significant impact on the performance of UV/H2O2 process. The NaIX with dealkalization was shown to be the most cost effective. The electrical energy per order (EEO) values for MtBE and tBA using low pressure high output UV lamps (LPUV) and 10mg/LH2O2 are 0.77 and 3.0kWh/kgal-order, or 0.20 and 0.79kWh/m³-order, respectively. For medium pressure UV high output lamps (MPUV), EEO values for MtBE and tBA are 4.6 and 15kWh/kgal-order, or 1.2 and 4.0kWh/m³-order, for the same H2O2 dosage. [Copyright 2008 Elsevier] Copyright of Water Research is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Abstract  Enantioenriched poly(hydroxy butyrate) (PHB) is a biodegradable polyester of significant commercial interest as an environmentally benign substitute of commodity polyolefines. We report on the design and development of new chiral indole-based ligand families and on their chromium(III) complexes as enantioselective catalysts for the conversion of propylene oxide and carbon monoxide to enantioenriched [beta]-butyrolactone, the key monomer for the production of PHB by ring-opening polymerization. The enantioselective carbonylation catalysts are based on new chiral tri- and tetradentate [N2O] and [N4] chromium(III) complexes containing chiral indolaldimine ligand scaffolds. The conceptual design of these ligands is inspired by Jacobsen's salicylaldimine lead structure; the key difference is an exchange of the salicyl-O-donor against an indole-N-donor, allowing additional structural diversity and stereoelectronic tuning by the indole substitution pattern. Synthetically, chiral indolealdimines are easily accessible from 7-formylindoles by standard Schiff base condensation with chiral amine building blocks; the 7-formylindoles in turn are synthesized from the corresponding 7-bromoindoles by the Rapoport synthesis, and the starting 7-bromoindoles are accessible from 2-bromoaniline by the classical Fischer indole synthesis. Three generations of chiral [N2O] and [N4] chromium(III) catalysts have been developed and evaluated in the enantioselective carbonylation of racemic propylene oxide with carbon monoxide using tetracarbonylcobaltate as the nucleophilic reagent for the insertion of carbon monoxide into the activated propylene oxide/chiral Lewis acid complex. The best catalyst out of 10 candidates showed at a temperature of 80 °C an activity of 37% conversion, 100% chemoselectivity, and 19% stereoselectivity.

Abstract  The methanol and methanol-chloroform (1:1) extracts of the freshly collected Haliclona exigua showed minumim inhibitory concentration (MIC) of 125 mu g/ml and 250 mu g/ml respectively in in vitro studies, but when both of these were tested in vivo in rats, only methanol-chloroform showed 80% inhibition of trophozoites at the dose of 900 mg/kg body weight against Entameba histolytica. Therefore only methanol-chloroform extract was further fractionated into four fractions (n-hexane, chloroform, n-butanol soluble and n-butanol insoluble fractions). Out of these, only n-hexane and n-butanol soluble fractions showed 80% inhibition of trophozoites at 900 mg/kg dose. Further the chromatography of the n-butanol fraction yielded araguspongin-C which showed promising results at different doses.

Abstract  The basic secretagogues, such as compound 48/80 (c48/80) and mastoparans, are widely used histamine-releasing agents and their mechanism of action is commonly attributed to a direct, receptor-bypassing property to activate the G(i/o) class of G proteins. We tested here whether c48/80 could directly stimulate [(35)S]guanosine-5'-[gamma-thio]triphosphate ([(35)S]GTPgammaS) binding to rat brain sections in an attempt to visualize the entire signaling pool of G(i/o) in its native neuroanatomical context. Instead of direct G(i/o) activation, c48/80 (100 microg ml(-1)) from various suppliers stimulated brain phospholipase D (PLD) activity, leading to the generation of endogenous phospholipids capable of activating brain white matter-enriched, G(i/o)-coupled lysophosphatidic acid (LPA) receptors. This response was sensitive to 1-butanol and was potently reversed by the LPA(1)/LPA(3) receptor-selective antagonist Ki16425 (IC(50) 59+/-13 nM, mean+/-s.e.m.), and showed age-dependent decline, closely reflecting known developmental regulation of the PLD-LPA(1) receptor axis in the CNS. In addition, c48/80 was found to modestly activate hippocampal 5-HT(1A) receptors in a pH-dependent and antagonist-sensitive manner. Consistent with the lack of direct G(i/o)-activating properties in brain sections, c48/80 showed no activity in classical membrane [(35)S]GTPgammaS binding assays. Instead, c48/80 from one particular manufacturer elicited non-specific effect in these assays, therefore challenging the previous interpretations regarding the compound's ability to activate G proteins directly. We conclude that c48/80 is not a receptor-bypassing general G protein activator but rather activates PLD, leading to generation of endogenous LPA receptor-activating phospholipids. This property may also contribute to the compound's ability to release histamine from mast cells.

Abstract  Aim: Transcranial Doppler sonography (TCD) is increasingly used in cerebrovascular disease for monitoring brain perfusion. It allows estimation of cerebral blood flow (CBF) by the measurement of cerebral blood flow velocity (CBFV). The CBFV as well as CB F are intimately associated with the intravascular CO2-concentration. Thus, hyper- or hypocapnia can be used to induce a defined range of blood flows. The aim of our study was the comparison of vasomotor reactivity assessed with simultaneous TCD and quantitative regional CBF-measurements (rCBF) by PET (serving as the reference method for in-vivo quantification of rCBF). Patients, methods: Six healthy young volunteers participated in this study. CBF was measured using O-15-butanol PET. A flow and dispersion-model was fitted to the measured time activity curves using arterial input curves. Each subject underwent five scans at five different end-tidal CO2 levels (EtCO2): 25, 32, 40, 48, and 55 mmHg. CBFV was assessed by continuous bilateral TO of the middle cerebral artery (MCA). Volumes of interest for rCBF determination were placed in grey matter of the prefrontal cortex (PFC) as determined from individual MRIs. Comparisons between the rCBF, EtCO2 and CBFV were carried out with regression and correlation analysis and paired t-tests. Results: Strong positive linear correlations of rCBF and CBFV with the CO2-concentration and linear relationships between rCBF and CBFV were found in each individual. Normalised CO2-reactivities measured by TO and PET were closely correlated. Conclusions: TCD-measurements of vascular reactivity in healthy volunteers show a high correlation to those acquired with PET that serves as the reference method of quantitative rCBF-measurement. The results of the MCA insonation are a close approximation of the rCBF changes induced by variations of EtCO2.

Abstract  This study was planned to investigate whether Lactuca sativa is capable of protecting neurons against glucose/serum deprivation (GSD)-induced cell injury, an in vitro model of brain ischemia. Two neuronlike cells, rat pheochromocytoma-derived cell line (PC12) and mouse neuroblastoma-like cell line (N2a), were cultivated for 24 h in standard media or for 6 and 12 h in GSD condition in the absence or presence of hydro-alcoholic extract (HAE), water fraction (WF), ethyl acetate fraction (EAF) or N-butanol fraction (NBF) of L. sativa. At the end of the experiments, the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium (MTT) assay. The L. sativa exhibited no cytotoxicity under standard condition unless at very high concentrations. Exposure of PC12 cells to GSD condition for 6 and 12 h led to 44 and 90% decrease in cell viability, respectively. The NBF and especially EAF significantly attenuated GSD-induced cell death. Also, GSD caused a significant reduction in N2a cell viability after 6 h (28%) and 12 h (84%). On the other hand, treatment of N2a cells with EAF blocked the cytotoxic effects of GSD condition. The present study revealed that intermediate polarity fraction of L. sativa (EAF) exerts neuroprotection and has the potential to be used as a new therapeutic strategy for common neurodegenerative disorders such as stroke.

Abstract  Hopbush (Dodoneae viscosa L.) is an evergreen bush type tree; that is used for hedges and green walls in parks, gardens and houses, in South East of Iran. Propagation by stem cuttings is quicker and cheaper than seed, if the cuttings set in convenient media and rooting hormone. In order to investigate the effects of different media and different concentrations of indole 3-butyric acid (IBA) on rooting of hopbush (Dodonea viscosa L.) cuttings, an experiment was conducted using mist system in greenhouse in spring 2010. The treatments were 3 different media: sand, perlite, and sand + perlite, (1+1 by volume), with 4 levels of IBA concentrations (0 m, 2000 ppm, 4000 ppm, and 6000 ppm). A randomized complete block with factorial design was used with 5 replications. The average and the means were compared by Duncun's multiple range test (1% and 5%); M STAT-C was used for comparing the interaction effects. The effect of medium on number of roots, percentage survival of stem cutting, root fresh weight and dry weight was significant, but on root length was not significantly affected. The effects of different concentrations of hormone on number of roots, percentage survival of stem cutting, root fresh weight and dry weight was significant. The interaction effect of media and hormone on root length was significant, too. The best result was obtained in perlite, with 4000 ppm IBA. The results showed that perlite medium and 4000 ppm IBA concentration can be suggested for soft wood cutting of hopbush.

Abstract  The theory of depression is dominated by the monoamine hypothesis but there is increasing evidence that beyond monoamines, glutamate (Glu) and gamma-aminobutyric acid (GABA) play an essential role in the pathogenesis of depression. In this study, the effect of alterations of GABA and Glu were investigated in the congenital learned helplessness paradigm. Proton magnetic resonance spectroscopy is an important monitoring tool to bridge the findings in clinical and preclinical studies. We found increased Glu/GABA ratios in the hippocampus and prefrontal cortex of placebo-treated (saline intraperitoneally) congenital learned helplessness rats versus wild-type rats, and a treatment-induced (desipramine 10 mg/kg intraperitoneally or electroconvulsive shock) decrease of this monoamine ratio in both brain regions. Our results corroborate previous findings of an amino-acid influence on the pathomechanisms of mood disorders.

Abstract  ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Xiangdan injection and its modifications have been used in traditional Chinese medicine for about hundreds years to alleviate pain and promoting blood.

AIM: To investigate the anti-hypoxia active fraction of Xiangdan injection.

MATERIALS AND METHODS: Xiangdan injection was extracted by ligarine, chloroform, acetic ether, n-butanol and water, represented respectively by A, B, C, D and E. Five extractions were group on the L12(2(5)) orthogonal designed table. NIH mices anti-hypoxia experiment under normal pressure with rats was adopted on the basis of orthogonal design, prediction pharmacodynamics model of TCM prescriptions was established, and the simulation bias was evaluated by combining two scatterplots. The anti-hypoxia active fraction of Xiangdan injection was determined by experiments.

RESULTS: The prediction model of TCM prescriptions established in this study can predict the drug actions for different formulas, and PE% <or= 25% was observed in 112 mice (93.3%).

CONCLUSION: As indicated in model prediction and experimental confirmation, the pharmacodynamic actions of the 5 formulas are all superior to that of the original formula, and ADE has the best effect.

Abstract  Present work describes the potent antidiabetic fraction from flowers of Cassia auriculata Linn. Hydromethanolic extract along with its ethyl acetate and n-butanol fractions were evaluated for antidiabetic activity in alloxan-induced diabetes in rats. The n-butanol fraction exhibited significant reduction (p<0.001) in blood glucose levels and was also found effective in restoring the blood lipids and proteins to normal level. The activity was found comparable with standard drug phenformin. The hydromethanolic extract and its fractions were subjected to preliminary qualitative chemical investigations which indicated the presence of phenolic compounds, carbohydrates, tannins, steroids and amino acids.

Abstract  The second order standard addition method and spectrofluorimetry were used for determination of ibuprofen enantiomers in human plasma and urine. The methodology was based on chiral recognition of ibuprofen by formation of an inclusion complex with a chiral auxiliary, beta-cyclodextrin, in the presence of 1-butanol. The strategy combines the use of PARAFAC, for extraction of the pure analyte signal, with the standard addition method, for determinations in presence of a matrix effect. A specific PARAFAC model was built for each sample and the scores were related to (S)-ibuprofen concentration using a linear regression in the standard addition method. Feasible results were obtained for determinations in the molar fraction range from 50 to 80% of (S)-ibuprofen, providing absolute errors lowers than 4.0% for plasma and urine. (C) 2010 Elsevier B.V. All rights reserved.

Abstract  The acrosome reaction (AR) is influenced by the action of several molecules such as GABA. P(4). and ET Objective: to determine the interaction between GABA / E(2). and GABA / P(4) in the AR. Methods: Washed human spermatozoa capacitated for 2 h were incubated in the following conditions: BWW medium alone (control) or BWW plus: P(4) E(2) GABA, GABA+ P(4) or GABA+ E(2) The % of AR was determined by FITC-PSA.'ReSults: Spermatozoa incubated with -GABA or P(4) showed higher % of AR: additionally, separate and simultaneous P(4) and GABA incubations showed no significant difference in the % of AR. GABA plus E, incubation showed lower % of AR than GABA only incubated spermatozoa. Conclusions: The AR would be modulated by inductors such as GABA and P4, there is not synergistic interaction between these molecules on AR induction: besides, there are inhibitory hormones such as E,. whose effect prevails in a combined GABA/E, incubation. The localisation of these compounds would determine timely AR occunence.

Abstract  This study investigated gamma-amino butyric acid (GABA) barley seeds for its potential uses such as in foodstuffs. A simple method was designed to produce "mochi" barley containing a high concentration of GABA. Scaled seeds of "mochi" barley (Hordeum vulgare) were soaked in a glutamic acid solution. After draining off the solution, the processed seeds were allowed to stand at room temperature overnight. During this process, glutamate decarboxylase in the mochi barley converted glutamic acid to GABA. For optimal conversion, seeds were scaled before soaking in a solution containing 0.3-1% glutamic acid at pH 4 to 8. (Received Sep. 27, 2010; Accepted Jan. 7, 2011)

Abstract  A novel microemulsion based on a mixture of diethyl L-tartrate (DET) and SDS was developed for the microemulsion EKC (MEEKC) determination of structurally related steroids. The system consisted of 0.5% w/w DET, 1.7% w/w SDS, 1.2% w/w 1-butanol, 89.6% w/w phosphate buffer (40 mM, pH 7.0), and 7% w/w ACN. With an applied voltage of +10 kV, a baseline separation of aldosterone (A), cortisone acetate (CA), dexamethasone (D), hydrocortisone (H), hydrocortisone acetate (HA), prednisolone (P), prednisolone acetate (PA), prednisone (Ps), triamcinolone (T), and triamcinolone acetonide (TA) could be achieved. Under the optimized conditions, the reproducibility of the retention time (n = 4) for most of the compounds was less than +/-0.8% with the exception of A, Ps, and T. The average number of theoretical plates was 18 800 plates/m. The results were compared with those achieved by the modified micellar EKC (MEKC). MEEKC showed obvious advantages over MEKC for the separation of highly hydrophobic substances. To further evaluate the system, we tested the MEEKC method by analyzing corticosteroids in a spiked urine sample.

Abstract  Phospholipase A(2) (PLA(2)) forms are expressed in spinal cord, and inhibiting spinal PLA(2) induces a potent antihyperalgesia. Here, we examined the antihyperalgesic effects after systemic and i.t. delivery of four compounds constructed with a common motif consisting of a 2-oxoamide with a hydrocarbon tail and a four-carbon tether. These molecules were characterized for their ability to block group IVA calcium-dependent PLA(2) (cPLA(2)) and group VIA calcium-independent PLA(2) (iPLA(2)) in inhibition assays using human recombinant enzyme. The rank ordering of potency in blocking group IVA cPLA(2) was AX048 (ethyl 4-[(2-oxohexadecanoyl)amino]butanoate), AX006 (4-[(2-oxohexadecanoyl)amino]butanoic acid), and AX057 (tert-butyl 4-[(2-oxohexadecanoyl)amino]butanoate) > AX010 (methyl 4-[(2-oxohexadecanoyl)amino]butanoate) and for inhibiting group VIA iPLA(2) was AX048, AX057 > AX006, and AX010. No agent altered recombinant cyclooxygenase activity. In vivo, i.t. (30 mug) and systemic (0.2-3 mg/kg i.p.) AX048 blocked carrageenan hyperalgesia and after systemic delivery in a model of spinally mediated hyperalgesia induced by i.t. substance P (SP). The other agents were without activity. In rats prepared with lumbar i.t. loop dialysis catheters, SP evoked spinal prostaglandin E(2) (PGE(2)) release. AX048 alone inhibited PGE(2) release. Intrathecal SR141617, a cannabinoid CB1 inhibitor at doses that blocked the effects of i.t. anandamide had no effect upon i.t. AX048. These results suggest that AX048 is the first systemically bioavailable compound with a significant affinity for group IVA cPLA(2), which produces a potent antihyperalgesia. The other agents, although demonstrating enzymatic activity in cell-free assays, appear unable to gain access to the intracellular PLA(2) toward which their action is targeted.

Abstract  In this paper, a micellar electrokinetic chromatography (MEKC) method combined with cation-selective exhaustive injection (CSEI) and sweeping was developed to separate and concentrate four tobacco-specific N-nitrosamines (TSNAs) including N'-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL). Experimental parameters affecting separation efficiency and enhancement factors were investigated in detail. Under the optimum MEKC condition, NAB, NNK, NNAL and iso-NNAL were baseline separated with high separation efficiencies and good peak shapes. Furthermore, with the preconcentration by CSEI-sweeping-MEKC, the sensitivity enhancement factors for NAB, NNK, NNAL and iso-NNAL in terms of peak areas ranged from 6.0×10(3) to 1.5×10(4), and the detection limits (LOD, S/N=3) of four TSNAs were in the range of 0.004-0.016μg/mL. In addition, this method had fairly good repeatability, and the RSDs of retention time and peak area were less than 1% and 5%, respectively. Finally, this method showed promising capabilities in the application of detecting and analyzing TSNAs in human urine samples.

Abstract  Aggregation of two porphyrin derivatives with carboxylic groups, 4-oxo-4-((4-(10,15,20-triphenyl-21H,23H-porphin-5-yl)phenyl)amino)butanoic acid (MAC) and 4,4',4'',4'''-[21H,23H-porphine-5,10,15,20-tetrayltetrakis(4,1-phenyleneimino)]tetrakis(4-oxo-butanoic acid) (TA4C), and their affinity to bovine serum albumin were investigated via absorption spectrometry, (1)H NMR and fluorescence spectrometry. MAC and its complexes with beta-cyclodextrin could form aggregates in an aqueous solution while TA4C was self-associated loosely. From the absorbance profiles of MAC in the titration of bovine serum albumin, hypochromicity was observed without any shift of the maximum absorbance wavelength. In both absorption spectra of TA4C in aqueous solutions and in solid state, three Q bands appeared in the visible region. In the measurements of absorption and fluorescence spectra upon titration of BSA, some spectral changes of TA4C were observed. The whole procedure of titration could be divided into three successive stages. The three-banded profiles of TA4C might be explained according to a loose dimer model.

Abstract  Lysophosphatidylcholine (LPC) is a bioactive lipid generated by phospholipase A2-mediated hydrolysis of phosphatidylcholine. In the present study, we demonstrate that LPC stimulates phospholipase D2 (PLD2) activity in rat pheochromocytoma PC12 cells. Serum deprivation induced cell death of PC12 cells, as demonstrated by decreased viability, DNA fragmentation, and increased sub-G1 fraction of cell cycle. LPC treatment protected PC12 cells partially from the cell death and induced neurite outgrowth of the cells. Overexpression of PLD2 drastically enhanced the LPC-induced inhibition of apoptosis and neuritogenesis. Pretreatment of the cells with 1-butanol, a PLD inhibitor, completely abrogated the LPC-induced inhibition of apoptosis and neurite outgrowth in PC12 cells overexpressing PLD2. These results indicate that LPC possesses the neurotrophic effects, such as anti-apoptosis and neurite outgrowth, through activation of PLD2.

Abstract  Substrate binding and the subsequent reaction are the two principal phenomena that underlie the activity of enzymes, and many enzyme-like catalysts were generated based on the phenomena. The single chain variable region fragment of antibody 2F3 (scFv2F3) was elicited against hapten GSH-S-DN2phBu, a conjugate of glutathione (GSH), butyl alcohol, and 1-chloro-2,4-dinitrobenzene (CDNB); it can therefore bind both GSH and CDNB, the substrates of native glutathione S-transferases (GSTs). It was shown previously that there is a serine residue that is the catalytic group of GST in the CDR regions of scFv2F3 close to the sulfhydryl of GSH. Thus, we anticipated that scFv2F3 will display GST activity. The experimental results showed that scFv2F3 indeed displayed GST activity that is equivalent to the rat-class GST T-2-2 and exhibited pH- and temperature-dependent catalytic activity. Steady-state kinetic studies showed that the Km values for the substrates are close to those of native GSTs, indicating that scFv2F3 has strong affinities for the substrates. Compared with some other GSTs, its kcat value was found to be low, which could be caused by the similarity between the GSH-S-DN2phBu and the reaction product of GSH and CDNB. These results showed that our approach to imitating enzymes is correct, which is that an active site may catalyze a chemical reaction when a catalytic group locates beside a substrate-binding site of a receptor. It is important to consider product inhibition in hapten design in order to obtain a mimic with a high catalytic efficiency.

Abstract  The heartwood or root of Dalbergia odorifera T. Chen is an important traditional Chinese medicine. Antioxidant activities of seed extracts from D. odorifera T. Chen were first investigated in this study. Ethanolic extracts were suspended in distilled water and partitioned successively with petroleum ether, ethyl acetate, n-butanol (n-BuOH) and water, yielding four extracts named as PE, EE, BE and WE, respectively. The EE exhibited the highest total phenolic, total flavonoid, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, linoleic acid and lard peroxidation inhibition, but lowest chelating ability. Liquid chromatography mass spectrometry (LC/MS) analysis of EE revealed that there was a predominant component with negative molecular ion [M-H](-) at m/z 373.2, a fragment at m/z 343.2 and UV Lambda(max) at 263 and 297nm. The mechanisms of antioxidant activities of seed extracts were exploited. Positive linear correlations were observed between reducing power and DPPH radical scavenging activity (R(2) = 0.836), and linoleic acid peroxidation inhibition (R(2) = 0.920), respectively. Similarly, high positive linear correlations of the total phenolic and total flavonoid with DPPH radical scavenging activity, reducing power and linoleic acid peroxidation inhibition were observed. This study therefore suggests that seeds of D. odorifera T. Chen have the potential to be used as natural antioxidants in food or pharmaceutical industry.