Efficient glycosidation of a phenyl thiosialoside donor with diphenyl sulfoxide and triflic anhydride in dichloromethane.
(41/177)
The formation of sialic acid glycosides with a thiosialic acid derivative, diphenyl sulfoxide, and trifluoromethanesulfonic anhydride is reported. With an excess of diphenyl sulfoxide, glycal formation can be completely suppressed and excellent yields are obtained for coupling to a wide range of primary, secondary, and tertiary acceptors. (+info)
Workshop overview: reassessment of the cancer risk of dichloromethane in humans.
(42/177)
The U.S. Environmental Protection Agency (U.S. EPA) classifies dichloromethane (DCM) as a "probable human carcinogen," based upon its risk assessment conducted in the late 1980s (http://www.epa.gov/iris/subst/0070.htm). Since that time, cancer risk-assessment practices have evolved, leading to improved scientifically based methods for estimating risk and for illuminating as well as reducing residual uncertainties. A new physiologically based pharmacokinetic (PBPK) model has been developed, using data from human volunteers exposed to low DCM levels, that provides new information on the human to human variability in DCM metabolism and elimination (L. M. Sweeney et al., 2004, Toxicol. Lett. 154, 201-216). This information, along with data from other published human studies, has been used to develop a new cancer risk estimation model utilizing probabilistic methodology similar to that employed recently by U.S. EPA for other chemicals (ENVIRON Health Sciences Institute, 2005, Development of population cancer risk estimates for environmental exposure to dichloromethane using a physiologically based pharmacokinetic model. Final Report to Eastman Kodak Company). This article summarizes the deliberations of a scientific peer-review panel convened on 3 and 4 May 2005 at the CIIT Centers for Health Research in Research Triangle Park, North Carolina, to review the "state of the science" for DCM and to critically evaluate the new information for its utility in assessing potential human cancer risks from DCM exposure. The panel (Melvin E Andersen, CIIT Centers for Health Research, Research Triangle Park, NC 27709; A. John Bailer, Miami University, Scripps Gerontology Center, Oxford, OH 45056; Kenneth S. Crump, ENVIRON Health Sciences Institute, Ruston, LA 71270; Clifford R. Elcombe, University of Dundee, Biomedical Research Centre, Dundee DD1 9SY, United Kingdom; Linda S. Erdreich, Exponent, 420 Lexington Avenue, Suite 1740, New York, NY 10170; Jeffery W. Fisher, University of Georgia, Department of Environmental Health Science, Athens, GA 30602; David Gaylor, Gaylor and Associates, LLC, Eureka Springs, AR 72631; F Peter Guengerich, Vanderbilt University, Department of Biochemistry, Nashville, TN 37232; Kenneth Mundt, ENVIRON Health Sciences Institute, Amherst, MA 01004; Lorenz R Rhomberg, Gradient Corporation, Cambridge, MA 021138; Charles Timchalk, Pacific Northwest National Laboratory, Richland, WA 99352), chaired by M.E.A., was composed of experts in xenobiotic metabolism and carcinogenic mechanisms, PBPK modeling, epidemiology, biostatistics, and quantitative risk assessment. Observers included representatives from U.S. EPA, CIIT, and Eastman Kodak Company (Kodak), as well as several consultants to Kodak. The workshop was organized and sponsored by Kodak, which employs DCM as a solvent in the production of imaging materials. Overall, the panel concluded that the new models for DCM risk assessment were scientifically and technically sound and represented an advance over those employed in past assessments. (+info)
Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in Ehrlich ascites carcinoma bearing mice.
(43/177)
The anticancer activity of dichloromethane extract of guduchi [Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Family: Menispermaceae (TCE)] in the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC mice receiving 25, 30, 40, 50 and 100 mg/kg, TCE showed a dose dependent elevation in tumor-free survival and a highest number of survivors were observed at 50 mg/kg TCE, which was considered as an optimum dose for its neoplastic action. The average survival time (AST) and median survival time (MST) for this dose were approximately 56 and 55 d, respectively when compared with 19 d of non-drug treated controls. Administration of 50 mg/kg TCE resulted in 100% long-term survivors (up to 90 d). An attempt was also made to evaluate the effectiveness of TCE in the various stages of tumor development, where 50 mg/kg TCE was administered intraperitoneally after 1, 3, 6, 9, 12 or 15 d of tumor inoculation and these days have been arbitrarily designated as stage I, II, III, IV or V, respectively for reasons of clarity. The greatest anticancer activity was recorded for stage I, II and III where number of long term survivors (LTS) was approximately 33, 25 and 17%, respectively. However, treatment of mice at stage IV and V did not increase LTS, despite an increase in AST and MST. The EAC mice receiving 50 mg/kg TCE showed a time dependent depletion in the glutathione (GSH) activity up to 12 h post-treatment and marginal elevation thereafter. This depletion in GSH was accompanied by a drastic elevation in lipid peroxidation (LPx) and a maximum elevation in LPx was observed at 6 h that declined gradually thereafter. TCE exerted cytotoxic effect on tumor cells by reducing the GSH concentration and increase in LPx simultaneously. (+info)
Application of physiologically based pharmacokinetic modeling in setting acute exposure guideline levels for methylene chloride.
(44/177)
Acute exposure guideline levels (AEGLs) are derived to protect the human population from adverse health effects in case of single exposure due to an accidental release of chemicals into the atmosphere. AEGLs are set at three different levels of increasing toxicity for exposure durations ranging from 10 min to 8 h. In the AEGL setting for methylene chloride, specific additional topics had to be addressed. This included a change of relevant toxicity endpoint within the 10-min to 8-h exposure time range from central nervous system depression caused by the parent compound to formation of carboxyhemoglobin (COHb) via biotransformation to carbon monoxide. Additionally, the biotransformation of methylene chloride includes both a saturable step as well as genetic polymorphism of the glutathione transferase involved. Physiologically based pharmacokinetic modeling was considered to be the appropriate tool to address all these topics in an adequate way. Two available PBPK models were combined and extended with additional algorithms for the estimation of the maximum COHb levels. The model was validated and verified with data obtained from volunteer studies. It was concluded that all the mentioned topics could be adequately accounted for by the PBPK model. The AEGL values as calculated with the model were substantiated by experimental data with volunteers and are concluded to be practically applicable. (+info)
Studies of the extraction of bilirubin from human amniotic fluid.
(45/177)
The recovery of unconjugated bilirubin from human amniotic fluid was studied using dichloromethane, chloroform/isopropanol (3:1 vol/vol), and chloroform/ methanol (3:1 vol/vol) extraction of human amniotic fluid that had been supplemented with bilirubin at various concentrations. Results were compared with those obtained with conventional chloroform extraction. Mean recoveries were found to be only 28% for chloroform and 25% for dichloromethane. When the polarity of chloroform was increased by the addition of an alcohol, the mean recovery increased to only 40% for chloroform/isopropanol and 38% for chloroform/ methanol. These results suggest that extraction methods for determination of amniotic fluid "delta OD(450)" (visible spectrophotometric absorbance [optical density] of bilirubin at 450 nm) tend to underestimate the result when compared with the nonextraction (direct-scan) method, on which the Liley Prognostication Chart is based. This finding should be clinically significant, particularly if extraction and direct-scan methods are used to monitor the condition of the same patient. (+info)
Diffusion coefficients of C60 and C60- in benzonitrile and dichloromethane solutions containing tetrabutylammonium perchlorate, measured by potential-step chronoamperometry.
(46/177)
The diffusion coefficients of C(60) in dichloromethane and benzonitrile solutions containing 0.1 M tetrabutylammonium perchlorate were determined by single potential-step chronoamperometry at small disk electrodes. The diffusion coefficients of C(60) were obtained by curve fitting of the chronoamperograms to a theoretical equation by Shoup and Szabo. The values were (1.4 +/- 0.3) x 10(-9) and (4.1 +/- 0.3) x 10(-10) m(2) s(-1), respectively (the errors are 95% confidence limits). The diffusion coefficients of C(60)(-) in these solutions were measured by double potential-step chronoamperometry. The ratios of the diffusion coefficients of C(60) to those of C(60)(-) were obtained from theoretical curves of the ratios of the current at the second potential step to the current at the first one. The values of the ratios were 1.2 +/- 0.2 and 1.0 +/- 0.3, respectively. (+info)
Use of accelerating solvent extraction for detecting non-steroidal anti-inflammatory drugs in horse feces.
(47/177)
Feces are a possible medium to be used for horse doping control. Efficient methods for detecting drugs in feces collected from various animals are routinely applied in institutes of food safety in Belgium. We have already tested whether they are applicable to horse feces. In this report, accelerated solvent extraction (ASE), an efficient method for extracting compounds from solid material, has been tested. ASE has been used to replace the diethyl ether liquid-liquid extraction step present in the method initially set up. This technique has been optimized for detecting several non-steroidal anti-inflammatory drugs (NSAIDs) in horse feces. Extraction recovery and limit of detection have been determined for several NSAIDs, such as meclofenamic acid, flunixin, vedaprofen, celecoxib, carprofen, diclofenac, and ketoprofen. The method has been successfully applied to meclofenamic acid, flunixin, and phenylbutazone post-administration feces samples, and the main metabolites identified in urine were also detected in feces. In the case of meclofenamic acid, the detection profile in feces presented in this report is in accordance with our previous finding in feces obtained with the original method. The use of ASE decreases the time necessary for sample preparation. This method is applicable on a large scale, which is useful for horse doping control. (+info)
Cytotoxic activity of the dichloromethane fraction from Vernonia scorpioides (Lam.) Pers. (Asteraceae) against Ehrlich's tumor cells in mice.
(48/177)
Vernonia scorpioides has been widely used in Brazil to treat skin problems and chronic wounds, such as ulcers of the lower limbs and diabetic lesions. In the present study, we investigated the effect of a dichloromethane (DCM) fraction of V. scorpioides leaf extract on Ehrlich ascitic and solid tumor-bearing mice. The animals were treated once a day with the DCM fraction at a concentration of 5 mg/kg, administered ip during and after the development of the tumor. The lifespan, weight, number and type of leukocytes, number of tumor cells, volume of solid and ascitic tumors were measured. The development of the tumor with pre-treated tumor cells in vitro with the DCM fraction (5 mg/kg) was analyzed and the animals were sacrificed after 7 days. The DCM fraction (5 mg/kg) totally inhibited tumor development when in direct contact with tumor cells, and also ascitic tumor development with in vitro treatment or when administered ip, in loco (after 7 days). Animals treated with the DCM fraction increased their lifespan ca. 2 weeks and maintained their body weight for 30 days. When applied immediately after the inoculation of the tumor cells in vivo, it totally abolished tumor development, with tumor development only decreasing when treatment was started 3 days after the tumor challenge. These data suggest an antineoplastic activity of the fraction. Oral or ip administration of DCM fraction (5 mg/kg) for 7 days did not reduce the solid tumor volume. The cytotoxic activity described here differs from the conventional immune suppressing profile of standard chemotherapy because it increases neutrophil influx to the peritoneal cavity. These results show that, besides exhibiting a tumoricidal activity, the DCM fraction also exhibits inflammatory activity. (+info)