ABSTRACT
Objective To improve the detection ability of laboratories, and to identify possible technical defects in the detection of dichloroacetic acid and trichloroacetic acid in drinking water. Methods A number of laboratories were organized to conduct interlaboratory determination of dichloroacetic acid and trichloroacetic acid in drinking water. Prefabricated standard series and intermediate samples were distributed. Data of determination were collected and statistically analyzed to evaluate the detection results. Results The slopes of dichloroacetic acid and trichloroacetic acid working curves were analyzed by Grubbs test. The analysis results showed that there were 1 outlier in the dichloroacetic acid data and 3 outliers in the trichloroacetic acid data, respectively. The determination results of the spiked samples of dichloroacetic acid and trichloroacetic acid were 1.5 and 4 times the actual value, respectively. Conclusion This investigation reveals that there exist some technical problems in the direct determination of dichloroacetic acid and trichloroacetic acid by gas chromatography, such as inappropriate selection of chromatographic conditions and injection port flow control, and incorrect way of spiking internal standards.
ABSTRACT
Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. Rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD+) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells' response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells' susceptibility to rapamycin treatment in vitro and in vivo.
Subject(s)
Humans , Sirolimus/pharmacology , Dichloroacetic Acid/pharmacology , Pyruvate Dehydrogenase Complex , TOR Serine-Threonine Kinases , Mechanistic Target of Rapamycin Complex 1 , Neoplasms/drug therapyABSTRACT
Objective@#To develop a headspace gas chromatography ( HS-GC ) assay for simultaneous determination of dichloroacetic acid ( DCA ) and trichloroacetic acid ( TCA ) in urine.@*Methods@#Urine samples (5 mL) were transferred to a 22 mL headspace bottle, added with 0.5 mL 10% sodium acetate solution , immediately sealed, and shaken evenly. The bottle was placed in the HS-GC system, and equilibrated at 90 ℃ for 60 minutes. The mixture was separated with the HP-INNOWAX chromatographic column, and the DCA and TCA concentrations were detected with the hydrogen flame detector.@*Results@#Under the optimal experimental conditions, the correlation coefficient of DCA and TAC was both > 0.999 0 within the range of 10-500.0 μg/L, and the lowest detection limits of DCA and TAC were 2.0 and 3.5 μg/L, with the spike recovery rate of 87.40% to 101.44%, and relative standard deviations of 1.89% to 3.25%. Of the 35 urine samples sampled from occupational populations, DCA and TCA were not detected.@*Conclusions@#The establishment of the HS-GAS assay through addition of sodium acetate and optimization of the headspace conditions, has high recovery and precision, which is effective to meet the requirements for daily determination of DCA and TCA in urine samples.
ABSTRACT
The investigation was carried out to determine the qualitative analysis of phytochemical screening and possible chemical components of Mukia maderaspatana (L.) (family: Cucurbitaceae), leaves GC-MS. The plant is an indigenous plant; traditionally it is used as an ingredient of various cocktail preparations and for the management of severe inflammatory disorders in Indian system of medicine. GC-MS analysis of hydroalcoholic extract lead to identification of 7 compounds. This analysis revealed that contains Mukia maderaspatana (L.) leaves mainly Dichloroacetic acid, 4-methylpentyl ester, 2-Butyn-1-ol, 4-methoxy and also showed the presence of other constituents like flavonoids, saponins, carbohydrates, steroids, tannins and phenolic compounds.
ABSTRACT
Sebaceous hyperplasia is a common disease in middle-aged adults. The lesions usually present as solitary or multiple yellowish tiny papules on the face. The areola, vulva and penis are rarely reported sites for this malady. There is no definitely successful treatment for sebaceous hyperplasia. A 35-year-old woman presented with a one-year-history of numerous asymptomatic tiny confluent papules arranged in yellowish plaques surrounding both nipples. Histologic examination showed multiple clustered sebaceous lobules around a centrally located, dilated sebaceous duct. The lesion was treated by applying dichloroacetic acid. After 6 weeks, the lesion had resolved leaving faint postinflammatory hypopigmentation. Herein, we report a rare case of areolar sebaceous hyperplasia that was treated with dichloroacetic acid.
Subject(s)
Adult , Female , Humans , Male , Dichloroacetic Acid , Hyperplasia , Hypopigmentation , Nipples , Penis , VulvaABSTRACT
The Arabidopsis thaliana glutathione S-transferases zeta class (AtGSTZ) is a multi-functional enzyme, which plays important role in cellular metabolism and environmental purification. Error-prone PCR and cycles of DNA shuffling were used to construct a mutagenesis library of AtGSTZ. The screening of the resultant libraries was carried out by a pH indicator dye-based colorimetric assay. Nine mutants which enhanced the dichloroacetic acid dechlorination activity were obtained. Among them, NN23 contained 25 amino acid substitutions with the activity improving 120%, whereas NN20 contained 24 amino acid substitutions with the activity improving 102%. EC1 contained 2 amino acid substitutions with the activity improving 47%. The rest 6 mutants contained one amino acid substitution with their activity increasing from 9% to 60%. The enzymatic characterization showed that all the evolved enzymes increased their catalytic efficiencies towards dichloroacetic acid and binding affinity towards glutathione whereas some of them increased the renaturability. However there is no obvious change in their thermostability. Based on these data, functional residues related to catalysis and refolding of AtGSTZ were discussed.
ABSTRACT
Objective To study the DNA damage induced by dichloroacetic acid(DCA) and trichloroacetic acid(TCA) which are from drinking water disinfection by-products. Methods V79 cells and hepatocytes of mice were treated with DCA and TCA for 1 hour and then were tested by comet assay. After stained by EB, tail length of the cells were observed and counted under the fluorescence microscope. Results Both DCA and TCA could result in the increasing of average tail length of the treated cells whether they were V79 cells or hepatocytes of mice and the dose-response relationships were seen. Conclusion Both DCA and TCA can cause DNA damage of mammalian cells and this may be related to the carcinogenic mechanism. DCA and TCA belong to genetic carcinogens.