Enhanced DC Dielectric Properties of Crosslinked Polyethylene Comprehensively Modified by the Grafting of a Multifunctional Voltage Stabilizer.

In this paper, a new multifunctional compound, 1,1'-(oxalylbis(4,1-phenylene))bis(1H-pyrrole-2,5-dione) (BVM), is grafted onto crosslinked polyethylene (XLPE) by radical-initiated grafting to play triple roles as a voltage stabilizer, space-charge inhibitor and crosslinking auxiliary and to achieve the purpose of comprehensively enhancing the DC dielectric properties of polymers while decreasing the type and number of additives. By analyzing the DC breakdown field strength, current density and space-charge distribution of the materials at different temperatures, it is demonstrated that BVM grafting can comprehensively and effectively enhance the electrical properties of the materials, with little dependence on temperature. The BVM molecule has two polar groups and an effective molecular structure that acts as a voltage stabilizer, thus enabling the introduction of dense, uniform, deeply trapped energy levels within the material to inhibit the space charge and to capture high-energy electrons to prevent damage to the material structure; however, the two functions do not affect each other. This is also consistent with first-principles calculations and quantum-chemical calculations. Gel content testing shows no effect on polymer crosslinking, even with a 27.8% reduction in the amount of the crosslinking agent di-isopropyl peroxide (DCP), which reduces the damage to the polymer's electrical resistance caused by the byproducts of DCP decomposition. Therefore, grafting multifunctional BVM compounds to improve the dielectric characteristics of polymers is a viable area of study in the development of high-voltage direct current (HVDC) cable materials.

Learning From Pixel-Level Label Noise: A New Perspective for Semi-Supervised Semantic Segmentation.

This paper addresses semi-supervised semantic segmentation by exploiting a small set of images with pixel-level annotations (strong supervisions) and a large set of images with only image-level annotations (weak supervisions). Most existing approaches aim to generate accurate pixel-level labels from weak supervisions. However, we observe that those generated labels still inevitably contain noisy labels. Motivated by this observation, we present a novel perspective and formulate this task as a problem of learning with pixel-level label noise. Existing noisy label methods, nevertheless, mainly aim at image-level tasks, which can not capture the relationship between neighboring labels in one image. Therefore, we propose a graph-based label noise detection and correction framework to deal with pixel-level noisy labels. In particular, for the generated pixel-level noisy labels from weak supervisions by Class Activation Map (CAM), we train a clean segmentation model with strong supervisions to detect the clean labels from these noisy labels according to the cross-entropy loss. Then, we adopt a superpixel-based graph to represent the relations of spatial adjacency and semantic similarity between pixels in one image. Finally we correct the noisy labels using a Graph Attention Network (GAT) supervised by detected clean labels. We comprehensively conduct experiments on PASCAL VOC 2012, PASCAL-Context, MS-COCO and Cityscapes datasets. The experimental results show that our proposed semi-supervised method achieves the state-of-the-art performances and even outperforms the fully-supervised models on PASCAL VOC 2012 and MS-COCO datasets in some cases.

A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery.

A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.

Biocompatibility, mechanical, and bonding properties of a dental adhesive modified with antibacterial monomer and cross-linker.

OBJECTIVES: This study investigated the antibacterial, cytotoxicity, and mechanical properties of a dental adhesive modified with quaternary ammonium monomer ((2-acryloyloxyethyl)dimethyldodecylammonium bromide) and cross-linker (bis(2-acryloyloxyethyl)methyldodecylammonium bromide). MATERIALS AND METHODS: Monomer (M), cross-linker (C), or a combination of these (M + C) were incorporated into adhesive Adper Single Bond Plus (SB) in 5, 10, or 25% (as wt%). A colony-forming unit and MTT assays were used to evaluate antibacterial properties against Streptococcus mutans and cell viability. Resin-dentin beams (0.9 ± 0.1 mm2) were evaluated for micro-tensile bond strength (µTBS) after 24 h, 6 months, and 3 years. Hourglass specimens were evaluated for ultimate tensile strength (UTS) after 24 h, 1 week, and 6 months. Micro-hardness measurements after softening in ethanol were taken as an indirect assessment of the polymer cross-linking density. Kruskal-Wallis, one-way ANOVA, two-way ANOVA, and Student's t test were used for analysis of the antibacterial, cytotoxicity, µTBS, UTS, and hardness data, all with a significance level of p < 0.05. RESULTS: 10%M and 25%M demonstrated a significant reduction in S. mutans relative to SB (p < 0.001). No differences in cytotoxicity were detected for any of the groups. After 6 months, no changes in µTBS were shown for any of the groups. After 3 years, all groups evidenced a significant decrease in µTBS (p < 0.05) except 5%M, 5%C, and 5%M + 5%C. All groups demonstrated either stable or significantly increased UTS after 6 months. Except for the cross-linker groups, a significant decrease in micro-hardness was shown for all groups after softening in ethanol (p < 0.05). CONCLUSIONS: A 5-10% of monomer may render the resin antibacterial without a compromise to its mechanical and bonding properties. CLINICAL RELEVANCE: Biomodification of a resin adhesive with an antibacterial monomer and cross-linker may help improve the life span of adhesive restorations.

Object Discovery From a Single Unlabeled Image by Mining Frequent Itemset With Multi-scale Features.

The goal of our work is to discover dominant objects in a very general setting where only a single unlabeled image is given. This is far more challenge than typical colocalization or weakly-supervised localization tasks. To tackle this problem, we propose a simple but effective pattern mining-based method, called Object Location Mining (OLM), which exploits the advantages of data mining and feature representation of pretrained convolutional neural networks (CNNs). Specifically, we first convert the feature maps from a pre-trained CNN model into a set of transactions, and then discovers frequent patterns from transaction database through pattern mining techniques. We observe that those discovered patterns, i.e., co-occurrence highlighted regions, typically hold appearance and spatial consistency. Motivated by this observation, we can easily discover and localize possible objects by merging relevant meaningful patterns. Extensive experiments on a variety of benchmarks demonstrate that OLM achieves competitive localization performance compared with the state-of-the-art methods. We also evaluate our approach compared with unsupervised saliency detection methods and achieves competitive results on seven benchmark datasets. Moreover, we conduct experiments on finegrained classification to show that our proposed method can locate the entire object and parts accurately, which can benefit to improving the classification results significantly.

A rapid LC-MS/MS method for simultaneous determination of quetiapine and duloxetine in rat plasma and its application to pharmacokinetic interaction study.

Combinations of new antidepressants like duloxetine and second-generation antipsychotics like quetiapine are used in clinical treatment of major depressive disorder, as well as in forensic toxicology scenarios. The drug-drug interaction (DDI) between quetiapine and duloxetine is worthy of attention to avoid unnecessary adverse effects. However, no pharmacokinetic DDI studies of quetiapine and duloxetine have been reported. In the present study, a rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of quetiapine and duloxetine in rat plasma. A one-step protein precipitation with acetonitrile was applied for sample preparation. The analytes were eluted on an Eclipse XDB-C18 column using the mixture of acetonitrile and 2 mM ammonium formate containing 0.1% formic acid at a gradient elution within 6.0 min. Quantification was performed in multiple-reaction-monitoring mode with the ion transitions m/z 384.4 â†’ 253.2 for quetiapine, m/z 298.1 â†’ 154.1 for duloxetine and m/z 376.2 â†’ 165.2 for IS (haloperidol), respectively. Good linearity was obtained in the range of 0.50-100 ng/mL for quetiapine (r2 = 0.9972) and 1.00-200 ng/mL for duloxetine (r2 = 0.9982) using 50 µL of rat plasma, respectively. The method was fully validated with accuracy, precision, matrix effects, recovery and stability. The validated data have met the acceptance criteria in FDA guideline. The method was applied to a pharmacokinetic interaction study and the results indicated that quetiapine had significant effect on the enhanced plasma exposure of duloxetine in rats under combination use. This study could be readily applied in therapeutic drug monitoring of major depressive disorder patients receiving such drug combinations.

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluorescent probe, via azide-alkyne click reactions. Subsequently, the allyl groups of the yielded PEG-grafted brush polymer are used to covalently link PTX and GEM onto the backbone via thiol-ene click reactions. The resulting BPDC exhibits an average hydrodynamic diameter of 111 nm. Sustained and simultaneous release of PTX and GEM from the BPDC is observed in phosphate buffered saline, with the release of PTX showing sensitivity in mild acidic conditions. In vitro studies using MIA PaCa-2 human pancreatic cancer cells illustrate the cellular uptake and cytotoxicity of the BPDC. In vivo, the BPDC possesses long blood circulation, tumor accumulation, and enables optical tumor imaging. Further development and testing is warranted for multifunctional conjugated brush polymer systems that integrate combination chemotherapies and imaging.

Polymer-antibiotic conjugates as antibacterial additives in dental resins.

Affecting the vast majority of human beings, dental caries is a premier concern of worldwide dental health. As the most commonly used restorative material to treat dental caries, resin-based composites (RBCs) lack antibacterial properties leading to quite limited restoration lifetimes. The objective of this study is to develop a polymer-antibiotic conjugate (PAC) as an effective antibacterial additive for RBCs. A monomer-antibiotic conjugate (MAC) with significant solubility was prepared by an esterification reaction of tert-butyloxycarbonyl (Boc)-protected ciprofloxacin (Cip) and 2-hydroxyethyl methacrylate (HEMA). The Cip-containing PAC with well-controlled molecular weight and composition was synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization of the MAC with HEMA (1 : 3 molar ratio), followed by the removal of Boc from the resulting copolymer. The antibacterial dental resin was then prepared by incorporating the PAC into a commercial resin, and their properties and antibacterial performance against Streptococcus mutans were tested. In vitro experiments revealed a very slow release of Cip, which resulted in significant killing effectiveness against Streptococcus mutans nonetheless, as observed through zone of inhibition assessment and SEM imaging. The promising antibacterial properties of these resins indicate that incorporating a PAC as an additive is a valid strategy to generate antibacterial materials for dental applications.

Rapid solid-phase extraction coupled with GC-MS method for the determination of venlafaxine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of venlafaxine combined with fluoxetine.

A rapid and sensitive gas chromatography with mass spectrometry method for the determination of venlafaxine in rat plasma has been developed and applied to a drug-drug interaction study of fluoxetine on pharmacokinetics of venlafaxine in rats. Rat plasma was spiked with 2% aqueous ammonia before subjected to preactivated C18 solid-phase extraction columns and eluted with methanol. No endogenous interferences were observed under optimal condition. The calibration curve was linear (R2  = 0.9994) in the range of 10-1000 ng/mL. The quantification limit of venlafaxine in rat plasma was 10 ng/mL. The accuracy was in the range of 85-110%, and the extraction recovery was no less than 50%. Both the intra- and interday precision were 5.0-10.7%. The concentration-time curve showed that plasma concentrations of the coadministration group (group B) were higher than that of single dose group (group A). Both values of Cmax (0.069 mg/L) and AUC0→∞ (0.291 mg h/L) in group B were statistically greater than that of Cmax (0.046 mg/L) and AUC0→∞ (0.181 mg·h/L) in group A (P < 0.05). The results indicated that a significant effect of fluoxetine was shown on the pharmacokinetics of venlafaxine, suggesting that drug-drug interactions are of concern for the treatment of depression with the combined use of venlafaxine and fluoxetine.

Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the simultaneous determination of 12 new antidepressants and 2 antipsychotics in whole blood by gas chromatography-mass spectrometry.

Antidepressant drugs are widely used in the treatment of different psychiatric disorders, as well as in conjunction with antipsychotics for the treatment of major depressive disorder. In this study, a simple and rapid ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) method was developed for the simultaneous determination of 12 new antidepressants (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide, melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram, paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting the UA-LDS-DLLME were optimized and the optimal conditions were as follows: 100µL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound stirring. Good linearity (R2≥0.991) was obtained at the concentration range of 15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N-desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The intra-day and inter-day precision were all less than 10%, and accuracy of intra-day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%, respectively. The extraction recoveries of most analytes were more than 60%. The UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy and good specificity for the simultaneous determination of 12 antidepressants and 2 antipsychotics, and has been successfully applied in a real case.

Two Fatal Intoxications with Cyanohydrins.

Cyanohydrins, also be called cyanoalcohols, are important industrial precursors to carboxylic acids and some amino acids. Acetone cyanohydrin (ACH) and formaldehyde cyanohydrin (glycolonitrile, FCH), which are the typical examples of cyanohydrins, are classified as extremely hazardous substances. As the cyanohydrins can readily decompose, and it is hard to find cyanohydrins in gastric contents and heart blood, the determination study in biological samples can be divided into two parts: the first is the determination of HCN by using a Prussian blue reaction and the HS-GC-MSD after derivatization by chloramine-T. The second is the determination of acetone or formaldehyde. In this part, headspace gas chromatography with flame ionization detector (HS-GC-FID) and solid phase microextraction (SPME)-gas chromatography with mass spectrometric detectors (GC-MSD) had been used. In this report, we reported two fatal intoxication cases of ACH and FCH; one person was killed by his wife by poisoning his food and the other was suicide by poison. Two real cases of ACH and FCH in human blood and gastric contents have been analyzed by using the above-mentioned method. The Prussian blue reaction was positive in the two cases. The peaks of acetone with retention times of 0.998 min appear in specimens of the deceased are consistent with the retention times of pure acetone. The peaks of formaldehyde with a retention time of 1.658 min appear in heart blood of the deceased, and the retention time of formaldehyde of the liquid is 1.674 min, which are consistent with the retention times of pure formaldehyde (1.673 min).

Phytochemical screening and chemical variability in volatile oils of aerial parts of Morinda morindoides.

Morinda morindoides is an important Liberian traditional medicine for the treatment of malaria, fever, worms etc. The plant was subjected to integrated approaches including phytochemical screening and gas chromatography mass spectrometry (GC-MS) analyses. Phytochemical investigation of the powdered plant revealed the presence of phenolics, tannins, flavonoids, saponins, terpenes, steroidal compounds and volatile oil. Steam distillation followed by GC-MS resulted in the identification of 47 volatiles in its aerial parts: 28 were in common including various bioactive volatiles. Major constituents of leaves were phytol (43.63%), palmitic acid (8.55%) and geranyl linalool (6.95%) and stem were palmitic acid (14.95%), eicosane (9.67%) and phytol (9.31%), and hence, a significant difference in the percentage composition of aerial parts was observed. To study seasonal changes, similarity analysis was carried out by calculating correlation coefficient (r) and vector angle cosine (z) that were more than 0.91 for stem-to-stem and leaf-to-leaf batches indicating considerable consistency.

Investigation of bi-enzymatic reactor based on hybrid monolith with nanoparticles embedded and its proteolytic characteristics.

The bottom-up strategy of proteomic profiling study based on mass spectrometer (MS) has drawn high attention. However, conventional solution-based digestion could not satisfy the demands of highly efficient and complete high throughput proteolysis of complex samples. We proposed a novel bi-enzymatic reactor by immobilizing two different enzymes (trypsin/chymotrypsin) onto a mixed support of hybrid organic-inorganic monolith with SBA-15 nanoparticles embedded. Typsin and chymotrypsin were crossly immobilized onto the mixed support by covalent bonding onto the monolith with glutaraldehyde as bridge reagent and chelation via copper ion onto the nanoparticles, respectively. Compared with single enzymatic reactors, the bi-enzymatic reactor improved the overall functional analysis of membrane proteins of rat liver by doubling the number of identified peptides (from 1184/1010 with trypsin/chymotrypsin enzymatic reactors to 2891 with bi-enzymatic reactor), which led to more proteins identified with deep coverage (from 452/336 to 620); the efficiency of the bi-enzymatic reactor is also better than that of solution-based tandem digestion, greatly shorting the digestion time from 24h to 50s. Moreover, more transmembrane proteins were identified by bi-enzymatic reactor (106) compared with solution-based tandem digestion (95) with the same two enzymes and enzymatic reactors with single enzyme immobilized (75 with trypsin and 66 with chymotrypsin). The proteolytic characteristics of the bi-enzymatic reactors were evaluated by applying them to digestion of rat liver proteins. The reactors showed good digestion capability for proteins with different hydrophobicity and molecular weight.

[Development of preparation of immobilized enzyme reactors in proteomics].

As an important part in "bottom-up" strategy of proteomics, immobilized enzyme reactors have great significance in the development of fast and more efficient protein analytical method, owing to its advantages of high speed and enzymatic efficiency, good stability and activity, easy operation, and the possibility of hyphenating with multiple detection instruments. In this paper, the preparation methods of immobilized enzyme reactors and their applications in proteomic investigation are introduced, focusing on the nature of enzymes, the immobilization methods and the carrier materials used for immobilizing enzyme. In recent years, the investigations are focused on increasing the immobilization amounts of enzyme, keeping enzymatic activity, improving enzymatic efficiency and decreasing nonspecific adsorption. The investigation results showed that by using novel carriers such as nanomaterial and monolith, increasing of hydrophilicity of carrier and tandem hydrolysis with multiple enzymes can greatly improve the performance of immobilized enzyme reactors and increase protein identification efficiencies.

Development of a field sampling method based on magnetic nanoparticles for the enrichment of pesticides in aqueous samples.

A field sampling method based on magnetic core-shell silica nanoparticles was developed for field sampling and the enrichment of low concentrations of pesticides in aqueous samples. The magnetic nanoparticles could be easily extracted from water samples by a custom-made magnetic nanoparticle collector. The recovery of 15 mg of magnetic particles from a 500 mL water sample was 90.8%. Mixtures of seven pesticides spiked into pure water and pond water were used as marker samples to evaluate the field sampling method. The average recoveries at three levels of spiking were in the range 60.0-104.7% with relative standard deviations <7.1%. The proposed method has good linearity with a correlation coefficient >0.9990 in the concentration range 0.5-15 µg L(-1). The results of the analysis of a sample of poisoned pond water indicate that this method is fast, convenient and efficient for the field sampling and enrichment of pesticides in aqueous samples.

A coumarin-based fluorescent probe for differential identification of sulfide and sulfite in CTAB micelle solution.

Sulfite and sulfide share several similarities in terms of chemical properties, such as nucleophilic and reducing reactivities. Therefore, they may disturb the detection of each other. In order to discriminate between these two kinds of sulfur-containing species, a new probe -N3 was developed, in which para-azidobenzenyl ketone was covalently incorporated to a coumarin fluorophore linked by a C=C double bond. Sulfite and sulfide can respectively react with the C=C double bond and the azido group to give different products, consequently, they can be differentially identified by UV-vis and fluorescence spectroscopy as well as by the naked eye. Selectivity and competition results reveal that -N3 is a good candidate for the detection of sulfide and sulfite. The bioimaging experiment demonstrates the potential of the -N3 probe for the differential imaging of sulfide and sulfite in living cells.

Prevalence of blood alcohol in fatal traffic crashes in Shanghai.

The objective of this project was to investigate the incidence of alcohol consumption in fatal traffic deaths in Shanghai, one of the largest cities in China. A study was conducted on 803 individuals killed in road accidents during the period 2009-2011, in terms of alcohol-positive rate, mean blood alcohol content (BAC), gender, age, vehicle type, pedestrian alcohol problem, single-vehicle vs multiple-vehicle crashes, and time of day. It was found that 28.9% of the drivers involved had a BAC≥0.20mg/mL (limit of civil offense) and 21.8% had a BAC≥0.80mg/mL (limit of criminal offense). The mean BAC of alcohol-positive drivers (with a BAC≥0.20mg/mL) was 1.51mg/mL. The vast majority of the drivers involved were males. With regards to age, the largest group was of drivers aged between 40 and 49 years group in both alcohol-negative cases (26.8%) and alcohol-positive cases (26.2%). Motorcycles were most likely to be involved, representing 34.4% of alcohol-negative crashes and 51.6% of alcohol-positive crashes. Very high BACs were common among alcohol-positive pedestrians, yet all female pedestrians were alcohol-negative. Single-vehicle crashes were over-represented in alcohol-positive cases. Alcohol-negative crashes and alcohol-positive crashes most often happened during the time period of 17:00-18:59 and 19:00-20:59, respectively.

Solid-phase extraction based on magnetic core-shell silica nanoparticles coupled with gas chromatography-mass spectrometry for the determination of low concentration pesticides in aqueous samples.

A simple and effective preconcentration method based on magnetic core-shell silica nanoparticles with C(18)-modified surface was developed for the analysis of pesticide residues in environmental water samples by gas chromatography-mass spectrometry. Several kinds of organophosphorous and pyrethroid pesticides including methamidophos, dichlorvos, orthene, phorate, dimethoate, carbofuran, bifenthrin, fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were used as model compounds to systematically evaluate the method. Various parameters, including the amounts of magnetic nanoparticles absorbents, extraction time, eluting solvent, eluting volume, and sample pH values were optimized. The optimized method affords low detection limits (signal-to-noise ratio = 3) from 0.001 to 0.008 µg/L, and shows good linearity with correlation coefficients over 0.9990 in the concentration range of 0.025-0.5 µg/L. Average recoveries at three spiked levels were in the range of 70.2-110.2% with relative standard deviations below 9.6%. A maximum enrichment factor of 1015 times was achieved. Analysis results of poisoned pond water indicate that this method is fast, convenient, and efficient for the detections of low-concentration pesticides in aqueous samples.

Anticancer constituents and cytotoxic activity of methanol-water extract of Polygonum bistorta L.

This study was specifically designed to identify anticancer constituents in methanol-water extract of Polygonum bistorta L. and evaluate its cytotoxicity. For this purpose methanol-water (40:60 v/v) extract was subjected to conventional preparative high pressure liquid chromatography and 13 fractions were obtained. Constituents of obtained fractions were separated and identified with the help of GC-MS and LC-DAD-ESI-MS. Anticancer phenolic compounds such as gallic acid, protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanillic acid, syringic acid, catechol, 4-methyl catechol, syringol and pyrogallol and fatty acids such as linoleic acid, myristic acid and palmitic acid were separated from different fractions. Fractions were evaluated for their cytotoxic activity on a rarely studied human hepatocellular carcinoma cell line (HCCLM3). 11 fractions showed good to strong cytotoxicity in a range of 200 µg/mL-800 µg/mL, whereas 2 fractions did not show any activity even at 800 µg/mL and no anticancer constituent was detected from them. 50 percent growth inhibition (GI50) values for five most active fractions were calculated and results were in a range of 86.5 (±3) µg/mL-126.8 (±3) µg/mL. 3 out of these 5 most active fractions were found to contain phenolic content in them whereas all other fractions containing phenolic content did possess cytotoxic activity that may suggest the importance of phenolic constituents in anticancer activity. Moreover, the results also showed a definite dose dependent relationship between amount of fractions and cytotoxic activity.

[Simultaneous determination of trihexyphenidyl, chlorpromazine and clozapine in blood by GC-MS].

OBJECTIVE: To develop a method to measure trihexyphenidyl, chlorpromazine and clozapine in human blood with GC-MS. METHODS: The specimens were alkalized (pH > 10) and extracted with V (benzene):V(ethyl acetate) = 1:1, and qualitatively analyzed using GC-MS-Full Scan with internal standard SKF525A. The specimens were alkalized (pH > 10) and extracted with V(benzene):V(ethyl acetate) = 1:1, and quantitatively analyzed using GC-MS-SIM with internal standard diazepam-d5. RESULTS: The lowest detection limits of trihexyphenidyl, chlorpromazine and clozapine were 0.3, 0.3 and 0.7 ng/mL (S/N > or = 3) respectively. The calibration curve in 20-10 000 ng/mL showed a good linear distribution. The recovery rate was 79.9% to 85.5%. The RSDs of intraday and interday were less than 5.1%. CONCLUSION: The established method was simple, sensitive and accurate for simultaneous determination of trihexyphenidyl, chlorpromazine and clozapine in human blood, and can be applied in forensic toxicological cases.