| Human Exposure Biomarkers - Permethrin as a Militarily-Relevant Model |
JUN 2007 |
23 pages |
| Authors:
Klaus G. Mross; Gina E. Adam; Daan Noort; Jeannot Zimmer; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA MILITARY PERFORMANCE DIV
|
 | Soldiers in operational environments are exposed to a variety of chemical substances. During deployment, they often move very rapidly from one "environment" to the other. Therefore ambient monitoring is very difficult and its outcome very complex to assess. Just as occupational and environmental assessments are becoming more common in industry, biomonitoring of chemical substances and their metabolites in body fluids of soldiers is the best way to calculate individual exposures. ... |
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| Endogenous 6-Hydroxymelatonin Excretion and Subsequent Risk of Breast Cancer: A Prospective Study |
MAR 2007 |
20 pages |
| Authors:
Paola C. Muti; ITALIAN NATIONAL CANCER INST REGINA ELENA ROME (ITALY)
|
| The prevalence of breast cancer is greatest in industrialized regions and exposure to light at night has been proposed as a potential risk factor. Modulation of melatonin secretion by light has been implicated in the causal pathway linking exposure to light and breast cancer risk. Recent evidence indicates that melatonin is a natural oncostatic agent capable of functioning through a variety of anti-proliferative, anti-oxidative, and immunostimulatory mechanisms. We conduct a ... |
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| Investigation of Hair Follicle and Plasma Biomarkers for Low-Level VX Vapor Exposure |
01 NOV 2006 |
8 pages |
| Authors:
E. M. LaFiandra; A. E. Chambers; J. Horsmon; J. J. Valdes; J. W. Sekowski; B. Benton; M. Horsmon; R. Mioduszewski; S. Thomson; C. Evans; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
| Currently, there are no field-ready and expedient assays able to determine whether someone has been exposed to very low-level chemical warfare agent (CWA). Furthermore, if it were known that a person had been exposed, there is a paucity of information regarding the potential for transient or persistent neurological or other injuries. While our laboratory is working to address both of these problems, our recent work toward finding a more expedient ... |
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| An Electrochemiluminescence-Based Competitive Displacement Immunossay for the Type-2 Brevetoxius in Oyster Extracts |
24 JUL 2006 |
7 pages |
| Authors:
Mark A. Poli; Victor R. Rivera; Dwayne D. Neal; Daniel G. Baden; Shawn A. Messer; Steven M. Plakas; Robert W. Dickey; Kathleen E. Said; Leanne Flewelling; David Green; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| A new competitive electrochemiluminescence-based immunoassay for the type-2 brevetoxins in oyster extracts was developed. The assay was verified by spiking known amounts of PbTx-3 into 80% methanol extracts of Gulf Coast oysters. We also provide preliminary data demonstrating that 100% acetone extracts, aqueous homogenates, and the clinical matrixes urine and serum can also be analyzed without significant matrix interferences. The assay offers the advantages of speed (2 h analysis time); ... |
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| Metabolism of Endosulfan-Alpha by Human Liver Microsomes and its Utility as a Simultaneous In Vitro Probe for CYP2B6 and CYP3A4 |
30 MAR 2006 |
33 pages |
| Authors:
Richard C. Casabar; Andrew D. Wallace; Ernest Hodgson; Randy L. Rose; NORTH CAROLINA STATE UNIV AT RALEIGH
|
| Endosulfan-alpha was metabolized to a single metabolite, endosulfan sulfate, in pooled human liver microsomes (Km = 9.8 muM, V(sub max) = 178.5 pmol/mg/min). With the use of recombinant cytochrome P450 (rCYP) isoforms, we identified CYP2B6 (K(sub m) = 16.2 muM, V(sub max) = 11.4 nmol/nmol CYP/min) and CYP3A4 (K(sub m) = 14.4 muM, V(sub max) = 1.3 nmol/nmol CYP/min) as the primary enzymes catalyzing the metabolism of endosultan-alpha, albeit CYP2B6 ... |
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| Spectrophotometric Analysis of the Cyanide Metabolite 1-Aminothiazoline-6-Carboxylic Acid |
2006 |
8 pages |
| Authors:
Steven I. Baskin; Ilona Petrikovics; Gennady E. Platoff; Gary A. Rockwood; Brian A. Logue; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Methods of directly evaluating cyanide levels are limited by the volatility of cyanide and by the difficulty of establishing steady- state cyanide levels with time. We investigated the measurement of a stable, toxic metabolite, 2-aminothiazoline-4- carboxylic acid (ATCA), in an attempt to circumvent the challenge of directly determining cyanide concentrations in aqueous media. This study was focused on the spectrophotometric ATCA determination in the presence of cyanide, thiocyanate (SCN-), cysteine, ... |
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| Simulating the Interactions of Genes, Proteins, and Metabolities in Cell-Like Entities |
SEP 2005 |
34 pages |
| Authors:
Brent D. Foy; WRIGHT STATE UNIV DAYTON OH
|
| The goal of this project was to create software to model Cell-Like Entities, and to perform initial simulations. A software package was written in Matlab that performs stochastic simulations using a Gillespie-based algorithm of biomolecular networks. Biochemical processes that can be modeled include binding, unbinding, transcription, translation, Michaelis-Menten, and n-th order processes. Models and parameters are defined using several text files. The software package was designed to enable simple porting ... |
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| Microfabricated Multianalyte Sensor Arrays for Metabolite Monitoring |
SEP 2005 |
36 pages |
| Authors:
Michael V. Pishko; Amos Mugweru; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| Development of simple and painless techniques of monitoring metabolites like glucose with increased frequency would be beneficial to diabetic patients. Implantable sensors for glucose have been under investigation for nearly three decades, Poor stability and sensitivity of these sensors limit their use in closed-loop delivery. In this work we have taken advantage of silicon micro-fabrication technologies to develop implantable redundant microsensor arrays with glucose oxidase molecules immobilized in photopolymerized and ... |
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| Aromatase Overexpression and Breast Cancer Development |
AUG 2005 |
9 pages |
| Authors:
Wei Yue; Jiping Wang; Sandra Gunselman; Ercole Cavalieri; Eleanor Rogan; Richard Santen; VIRGINIA UNIV CHARLOTTESVILLE
|
| Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite or estrogen, which causes DNA damage and tumors in animal models. In situ synthesis of estrogen in the breast through aromatase results in high tissue estrogen concentrations. We hypothesized that overexpression of aromatase in breast tissue increases tissue estradiol concentrations and consequent genotoxic metabolites, and eventually causes breast cancer. To test our hypothesis, we stably expressed aromatase cDNA in ... |
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| Endogenous 6-Hydroxymelatonin Excretion and Subsequent Risk of Breast Cancer: A Prospective Study |
MAR 2005 |
41 pages |
| Authors:
Paola C. Muti; STATE UNIV OF NEW YORK AT BUFFALO AMHERST
|
| The prevalence of breast cancer is greatest in industrialized regions and exposure to light at night has been proposed as a potential risk factor. Modulation of melatonin secretion by light has been implicated in the caupathway linking exposure to light and breast cancer risk. Recent evidence indicates that melatonin is a naturaoncostatic agent capable of functioning through a variety of anti-proliferative anti-oxidative and immunostimulatory mechanisms. We conduct a study to ... |
|
| Gas Chromatographic/Mass Spectrometric Differentiation of Atenolol, Metoprolol, Propranolol, and an Interfering Metabolite Product of Metoprolol |
OCT 2004 |
9 pages |
| Authors:
Mike K. Angier; Russel J. Lewis; Arvind K. Chaturvedi; Dennis V. Canfield; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| Pilots who successfully control their hypertension with medications, diet, and/or exercise can be medically certified to fly an aircraft. At the present time, approximately 8% of active pilots are designated as "hypertensive with medication" by the Federal Aviation Administration (FAA). One of the groups of antihypertensives is the beta-blocker. Of this group, atenolol, metoprolol, and propranolol are commonly prescribed, and they also have chemical and structural similarities. The FAA's Civil ... |
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| Breast Cancer Risk in Relation to Urinary Estrogen Metabolites and Their Genetic Determinants: A Study Within the Dutch "DOM" Cohort |
SEP 2004 |
7 pages |
| Authors:
Rudolf J. Kaaks; INTERNATIONAL AGENCY FOR RESEARCH ON CANCER LYONS (FRANCE)
|
| We are conducting a large case-control study, nested within a prospective cohort, to estimate relative risk of breast cancer in post- menopausal women by levels of urinary estrogens and estrogen metabolites, and to examine the association between the concentrations of these hormones and breast cancer risk with polymorphic variations of a series of candidate genes, known to be implicated in the regulation of estrogen metabolites synthesis. In this second year ... |
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| Aromatase Overexpression and Breast Cancer Development |
AUG 2004 |
13 pages |
| Authors:
Wei Yue; Jiping Wang; Yuebai Li; Sandra Gunselman; Ercole Cavalieri; VIRGINIA UNIV CHARLOTTESVILLE
|
| Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite of estrogen, which causes DNA damage and tumors in animal models. In situ synthesis of estrogen in the breast through aromatase results in high tissue estrogen concentrations. We hypothesized that overexpression of aromatase in breast tissue increases tissue estradiol concentrations and consequent genotoxic metabolites, and eventually causes breast cancer. To test our hypothesis, we stably expressed aromatase cDNA in ... |
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| Low Melatonin Production During Adulthood - Phase 2: Association with Levels of Hydroxyl Radical Scavenging and DNA Damage |
AUG 2004 |
5 pages |
| Authors:
Eugene L. Sobel; Zoreh Davanipour; Henrik Poulsen; FRIENDS RESEARCH INSTITUTION INC LOS ANGELES CA
|
| The primary purpose of the proposed study is to develop cross-sectional evidence concerning whether or not lower melatonin production levels are associated with increased oxidative DNA guanine damage. If the results of this study are supportive, then confirmatory studies would be warranted, followed by prospective chemoprevention studies of melatonin supplementation. Adjuvant cancer treatment studies have not identified any serious melatonin toxicities. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI MS/MS) ... |
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| Aromatase Overexpression and Breast Cancer Development |
AUG 2004 |
9 pages |
| Authors:
Wei Yue; Jiping Wang; Yuebai Li; Sandra Gunselman; Ercole Cavalieri; Eleanor Rogan; Sandra Fernandez; Jose Russo; VIRGINIA UNIV CHARLOTTESVILLE
|
| Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite of estrogen, which causes DNA damage and tumors in animal models. In situ synthesis of estrogen in the breast through aromatase results in high tissue estrogen concentrations. We hypothesized that overexpression of aromatase in breast tissue increases tissue estradiol concentrations and consequent genotoxic metabolites, and eventually causes breast cancer. To test our hypothesis, we stably expressed aromatase cDNA in ... |
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| Estrogens, Genetic Polymorphisms and Breast Cancer Risk |
JUL 2004 |
6 pages |
| Authors:
Michael N. Okobia; Clareann H. Bunker; Lewis Kuller; Robert E. Ferrell; Stanley N. Anyanwu; Emmanuel R. Ezeome; Emmanuel E. Uche; PITTSBURGH UNIV PA
|
| This study is aimed at evaluating the role of polymorphisms in the genes encoding enzymes responsible for the biosynthesis and degradation of estrogens and its metabolites in susceptibility to breast cancer in Nigerian women. A case-control study is being undertaken to investigate the exposure level to estrogen and its metabolites in these women by examining the genotype frequencies of the genes encoding aromatase, estrogen hydroxylase and catechol- O-methyltransferase, the three ... |
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| Cellular Retinoic Acid Binding Protein and Breast Cancer |
MAY 2004 |
20 pages |
| Authors:
Leslie J. Willmert; CORNELL UNIV ITHACA NY
|
| In attempts to understand how the signaling by retinoic acid (the active vitamin A metabolite) is regulated we have been studying the retinoic acid binding protein called CRABP-II. These studies revealed that CRABP-II acts to enhance the transcriptional activities of RA and that it does so by directly delivering the hormone to its cognate transcription factor, RAR. Consequently CRABP-II dramatically sensitized cultured mammary carcinoma cells to RA-induced growth inhibition. Similarly, ... |
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| Molecular Mechanisms of Essential Fatty Acids and Metabolites in Regulation of Prostate Cancer Cells |
MAR 2004 |
27 pages |
| Authors:
Charles Y. Young; MAYO CLINIC ROCHESTER MN
|
| Prostate cancer is a heterogeneous disease for which the only effective treatments for organ-confined cancer at this time include radical surgery, radiation or androgen ablation/hormonal therapy. But advanced prostate cancer is almost no cure. Effective ways to prevent and/or treat advanced prostate cancer are needed. Our recent work has shown that a terminal metabolite, 15-deoxy-delta l2, 14-prostaglandin J2 (15d-PGJ2), of some essential polyunsaturated fatty acids can induce cell death of ... |
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| Ethanol Origin in Postmortem Urine: An LC/MS Determination of Serotonin Metabolites |
NOV 2003 |
18 pages |
| Authors:
Robert D. Johnson; Russell J. Lewis; Dennis V. Canfield; C. L. Blank; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of ... |
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| Phase I Induction and Estrogen Metabolism in Women with and Without Breast Cancer and in Response to a Dietary Intervention |
OCT 2003 |
19 pages |
| Authors:
James R. Hebert; SOUTH CAROLINA UNIV COLUMBIA
|
| The combined case-comparison study and randomized controlled trial (RCT) of 90 women is based on our prior edpidemiologic work (1-6) indicating that vegetables in the Brassica genus (e.g., broccoli, cauliflower, brussel sprouts) can modify estrogen metabolism by causing l7beta- estradiol (E2) to be metabolized to 2-hydroxyestrone (2HE) rather than 16alpha-hydroxyestrone (l6HE) thus producing a cascade of effects protective against breast cancer (2). Our plan is to enroll 45 postmenopausal women ... |
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| Studies on the Novel Anticancer Agents Metabolically Formed from 17- Beta-Estradiol |
JUN 2003 |
6 pages |
| Authors:
Anthony J. Lee; SOUTH CAROLINA UNIV RESEARCH FOUNDATION COLUMBIA
|
| By using NMR and mass spectrometric analyses, we determined the structures of Xl and X2, two representative nonpolar estrogen metabolites, which were metabolically formed following multiple large-scale incubations of 17 beta- estradiol with human CYP3A4 and NADPH. Both Xl and X2 were unequivocally identified to be the dimers of l7 beta-estradiol, connected together through a diaryl ether bond between a phenolic oxygen atom of one l7 beta-estradiol molecule and the ... |
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| Role of Map Kinase in Mediating the Effects of Vitamin D3 Metabolites on Growth Plate Chondrocytes |
MAY 2003 |
75 pages |
| Authors:
Ehland Haris; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
|
| Endochondral bone formation involves a developmental cascade of cell differentiation and maturation, which culminates in mineralization of the extracellular matrix by chondrocytes. The process is required for normal long bone growth and in certain kinds of bone repair. Vitamin D3 plays an important regulatory role in chondrocyte differentiation and maturation and therefore is essential for proper endochondral ossification. The vitamin D3 family contains two metabolites, 1alpha,25(OH)2D3 and 24R,25(OH)2D3, which have ... |
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| Molecular Mechanisms of Essential Fatty Acids and Metabolites in Regulation of Prostate Cancer Cells |
MAR 2003 |
20 pages |
| Authors:
Charles Y. Young; MAYO CLINIC ROCHESTER MN
|
| Prostate cancer is a heterogeneous disease for which the only effective treatments for organ-confined cancer at this time include radical surgery, radiation or androgen ablation/hormonal therapy. But advanced prostate cancer is almost no cure. Effective ways to prevent and/or treat advanced prostate cancer are needed. Our recent work has shown that a terminal metabolite, 15-deoxy-deltal2,l4- prostaglandin J2,(15d-PGJ2), of some essential polyunsaturated fatty acids can induce cell death of human and ... |
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| Genetic Polymorphisms, Estrogens, and Breast Density |
AUG 2002 |
9 pages |
| Authors:
Gertraud Maskarinec; HAWAII UNIV HONOLULU
|
| Mammographic density appears to be a strong predictor of breast cancer risk. Endogenous steroid hormones have been shown to be important in the development and progression of breast cancer. Because some metabolites of endogenous estrogens may have more estrogenic effects than others, genetically determined differences in biosynthesis and metabolic pathways of estrogens may affect breast cancer risk. This study will address the following specific aims: 1. To examine the relation ... |
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| Soy Metabolites, Isoflavones in Cell Growth and Apoptosis |
JAN 2002 |
14 pages |
| Authors:
Fazlol Sarkar; WAYNE STATE UNIV DETROIT MI
|
| The purpose of our investigation was to elucidate the molecular mechanism(s) by which genistein elicits its biological effects on non- tumorigenic and tumorigenic breast epithelial cells. We have completed all our tasks as planned and our major findings are: (a) that genistein inhibits cell cycle by modulating genes that are important cell cycle regulators, (b) that genistein induces apoptotic cell death in breast cancer cells irrespective of their status of ... |
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| Metabolism of Perchloroethylene and 1,1,1,2-Tetrachloroethane After Carbon Tetrachloride Pretreatment in B6C3F1 Mice |
AUG 2000 |
23 pages |
| Authors:
Deirdre A. Mahle; Richard J. Godfrey; Gerry W. Buttler; Jeffrey W. Fisher; MANTECH GEO-CENTERS JOINT VENTURE DAYTO OH
|
| Risk assessments for chlorinated solvents are typically only done for single chemicals, and clean up costs are based on these assessments. However, groundwater and drinking water supplies are usually contaminated with multiple compounds. The most commonly used approach for assessing risks to multiple chemical exposures assumes additivity of response. This study investigates the effect of exposure to mixtures of carbon tetrachloride and 2 other chlorinated solvents, perchloroethylene and 1,1,1 ,2-tetrachloroethane. ... |
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| Inhibition of Invasiveness and Motility of Human Breast Cancer Cells by Sphingosine-1-Phosphate |
AUG 1999 |
92 pages |
| Authors:
Fang Wang; GEORGETOWN UNIV WASHINGTON DC
|
| Sphingosine-1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits chemoinvasiveness of the aggressive, estrogen independent MDA-MB-23 1 human breast cancer cell line. Similar to many other cell types, SPP stimulated proliferation of MDA- MB-231 cells, albeit to a lesser extent. Treatment of MDA- MB-231 cells with SPP had no significant effect on their adhesiveness to Matrigel, and only high concentrations of SPP partially inhibited matrix metalloproteinase 2 ... |
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| Soy Metabolites, Isoflavones in Cell Growth and Apoptosis |
AUG 1999 |
59 pages |
| Authors:
Fazlul Sarkar; WAYNE STATE UNIV DETROIT MI
|
| Epidemiological studies suggest that the phytochemicals, genistein and daidzein, are the anti-cancer agents found in Asian diets which contribute to a decreased breast cancer risk. In the current study, we investigated the molecular mechanism by which genistein inhibits cell growth and induces apoptosis. Our data show that genistein induces G2/M cell cycle arrest, dose- dependent cell growth inhibition, down-regulation of Bcl-2 and cyclin B, and ... |
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| Soy Metabolites, Isoflavones in Cell Growth and Apoptosis |
AUG 1998 |
12 pages |
| Authors:
Fazlul Sarkar; WAYNE STATE UNIV DETROIT MI
|
| The hypothesis to be tested in this proposal was that soy metabolites selectively eliminate aberrant breast epithelial cells (tumor cells) by altering the expression of specific cell cycle regulatory genes which, in turn, causes cell cycle arrest and induces apoptosis. Tumors often occur as a result of uncontrolled and deregulated cell cycle caused by an imbalance of CKIs and CDKs. Current knowledge dictates that the deregulation of many classes of ... |
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| Analogs of Estrogen Metabolites as Probes of Estrogen-Induced Tumorigenesis |
JUL 1998 |
68 pages |
| Authors:
Abhijit S. Bbat; OHIO STATE UNIV COLUMBUS
|
| 2- AND 4-Hydroxyalkyl estradiols were synthesized as biochemically stable Catechol estrogen mimics. These analogs were used as chemical probes to evaluate the proposed involvement of catechol estrogens in the initiation of breast cancer. Potentiometric studies performed in PBS buffer at pH 7.4 showed that catechol estrogens were able to undergo redox cycling whereas the Hydroxyalkyl estradiols unable to redox cycle. In agreement with potentiometric ... |
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| Zebra Mussel Research Technical Notes. Use of Microorganisms and Their Metabolites for Zebra Mussel Control. Section 3 - Control Strategies |
JAN 98 |
2 pages |
| Authors:
Ralph Mitchell; Ji-Dong Gu; ARMY ENGINEER WATERWAYS EXPERIMENT STATION VICKSBURG MS
|
| The control of zebra mussel fouling has largely involved chemical and/or physical measures, many of which are expensive and environmentally unacceptable. Chlorination and other biocides are often used to eradicate mussel fouling. Intensive posttreatment cleaning is also used, because of the strong attachment of zebra mussel byssal threads to surfaces. Novel methods of control which are environmentally acceptable are needed. Biological control, which has not been extensively explored, may yield ... |
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| Stereochemical Determination of Selegiline Metabolites in Postmortem Biological Specimens |
JUL 97 |
13 pages |
| Authors:
T. C. Kupiec; A. K. Chaturvedi; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| The Federal Aviation Administration's Toxicology and Accident Research Laboratory determines the presence of drugs, volatiles, and primary combustion gases in biological samples from aircraft accident victims and also establishes any medical condition for which the drugs might have been taken. In this study, findings related to an aircraft accident are reported. Along with biological specimens from the pilot of this fatal accident, two types of tablets found at the accident ... |
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| Analogs of Estrogen Metabolites as Probes of Estrogen-Induced Tumorigenesis |
JUL 97 |
83 pages |
| Authors:
Abhijit S. Bhat; OHIO STATE UNIV COLUMBUS
|
| Estrogens play a pivotal role in 50-60% of breast cancer case amongst females. Estrogen metabolites have been implicated as mediators in the development of estrogen-induced tumors. The catechol estrogens are particularly interesting chemically since they are prone to undergo further oxidative metabolism and form reactive intermediates like quinones, semiquinones and arene oxides. These reactive intermediates can undergo redox cycling in presence of the metal ions associated with cellular DNA and ... |
|
| Dose-Response Correlation of Methadone and its Metabolite EDDP in Human Hair. Start of the Third Series and Analysis of the Samples of the Second Test Series |
31 MAR 96 |
3 pages |
| Authors:
NAVAL RESEARCH LAB WASHINGTON DC
|
| We were able to arrange for the patients of two further Methadon practices, that of Dr. Sachtleben in Pirmasens and Dr. Lueg in Kaiserslautem, to take part in our study. They were treated in the same manner as described in our previous Technical Reports. In this new series, the applied sweat patches were generally well accepted. Up until now only one patient (L2) has complained about irritations from the last ... |
|
| Dose-Response Correlation of Methadone and its Metabolite EDDP in Human Hair. Completion of the Second and Preparation of the Third Test Series |
31 DEC 95 |
2 pages |
| Authors:
NAVAL RESEARCH LAB WASHINGTON DC
|
| Analogous to the first test series, the following steps were undertaken with each of the subjects of the Methadone distribution center in Saarbruecken: (a) Five sweat patches were applied and then removed after one, two, three, four, and six days respectively. Contrary to the patients of Dr. Franta's practice, none of the subjects complained about allergic reactions or irritations. Yet, several of the sweat patches were lost, and a few ... |
|
| Gas Uptake Kinetics of 1,1,1 ,3,3,3-Hexafluoropropane (HFC-236fa) and Identification of its Potential Metabolites |
NOV 1995 |
48 pages |
| Authors:
Allen Vinegar; Gerry W. Buttler; Melanie C. Caracci; James D. McCafferty; GEO-CENTERS INC NEWTON CENTRE MA
|
| As part of the Navy's efforts to eliminate ozone depleting substances, a new refrigerant, HFC-236fa, has been developed through a joint EPA/Navy effort. This refrigerant is a replacement for refrigerant CFC-114 which is used in centrifugal chillers aboard surface ships and submarines. The aim of these studies was to measure tissue:air partition coefficients and to describe the kinetics of 1,1,1,3,3,3-hexafluoropropane (HFC-236fa) via recirculating gas uptake exposure methods and to look ... |
|
| Ammonium Dinitramide: An EPR/ENDOR Study |
SEP 1995 |
20 pages |
| Authors:
L. Steel-Goodwin; D. M. Pace; A. J. Carmichael; ARMSTRONG LAB WRIGHT-PATTERSON AFB OH TOXICOLOGY DIV
|
| Ammonium dinitramide (NH4N(NO22,ADN) is an oxidizer with potential applications in aerospace technology. Based on its chemical formula, ADN can decompose to form reactive nitrogen metabolites (RNMs). The decomposition characteristics of ADN powder following exposure to non-ionizing and ionizing radiation were studied. Electron paramagnetic resonance (EPR) spectroscopy was used to determine if radiation induces chemical change in ADN by formation of free radicals. Most free ... |
|
| Role of Metabolites in Aviation Forensic Toxicology |
AUG 95 |
9 pages |
| Authors:
Arvind K. Chaturvedi; Dennis V. Canfield; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| In aviation accident investigations, specimens from fatal aircraft victims are analyzed for drugs. Their presence indicates exposure to drugs and suggests possible associated medical conditions for which they might have been taken. As drugs are mostly present in therapeutic to subtherapeutic levels in aviation forensic toxicology cases, determination of parent drugs and their metabolites in multi specimens is of significance. Although chemically reactive metabolites are difficult to detect, physiologically active ... |
|
| Effect of Transforming Growth Factor Beta (TGF Beta) and Vitamin D3 Metabolites on Protein Kinase C Mediated Signal Transduction in Rat Costochondral Chondrocyte Cultures |
MAY 95 |
103 pages |
| Authors:
Scott A. Mackey; TEXAS UNIV AT SAN ANTONIO GRADUATE SCHOOL OF BIOMEDICAL SCIENCES
|
| It is Imown that vitamin D3 metabolites and transforming growth factor % (TOF-J3) regulate proliferation and differentiation of chondrocytes isolated from the growth zone or resting zone of rat costochondral cartilage. It was hypothesized that both TGF-% and the vitamin D metabolites play a role in signal transduction in the rat costochondral chondrocyte model and that the regulation of protein kinase C by these metabolites would be cell maturation- dependent. ... |
|
| Alteration in Neurotransmitters and their Metabolite Levels in 1,3,5- Trinitrobenzene-Treated Sprague-Dawley Rats |
APR 1995 |
42 pages |
| Authors:
Latha Narayanan; Daniel J. Caldwell; Clay R. Miller; MANTECH-GEOCENTERS JOINT VENTURE DAYTON OH
|
| 1 ,3,5- trinitrobenzene (TNB), a class-A explosive, is an anthropogenic environmental contaminant found in effluent released from facilities that synthesize, produce or demilitarize munitions, or in the leachate from disposal of solid 2,4,6-trinitrotoluene (TNT) wastes. We have reported that rats exposed to TNB show signs of neurological stress (head tilting, loss of equilibrium and "cork screw" like motion) and bilateral lesions in medulla oblongata and cerebral peduncle. The underlying biochemical ... |
|
| Isolated Perfused Small Intestine-Application for Absorption and Metabolism of Trichloroethylene in the Fischer 344 Rat |
APR 1995 |
23 pages |
| Authors:
C. M. Garrett; D. A. Mahie; S. Stavrou; J. C. Lipscomb; GEO-CENTERS INC NEWTON CENTRE MA
|
| Exposure by ingestion is the major route of exposure to toxic substances, particularly chemicals found in groundwater. Toxic substances which enter the body by this route may be metabolized to toxic intermediates which may then be exposed in high concentrations to the liver through the "first pass effect", a physiological phenomenon occurring in the hepatic portal circulation. Because liver tumors in rodents are often the toxicity extrapolated to determine the ... |
|
| Quantitative Structure Activity Relationships of Chlorinated Alicyclic Compounds |
14 MAR 95 |
35 pages |
| Authors:
Janice E. Chambers; MISSISSIPPI STATE UNIV MISSISSIPPI STATE COLL OF VETERINARY MEDICINE
|
| A quantitative structure-activity relationship study was performed on 33 chlorinate alicyclic compounds, most of which are chlorinated cyclodiene insecticides or their structural analogs. Their action on the t- butylbicyclophosphorothionate (TBPS) binding site of the gammaaminobutyric acid (GABA) receptor/chloride ionophore complex is being correlated with their lipophilicity, electronegativity and/or molecular connectivity characteristics. The biological parameters were investigate at Mississippi State University. The in vitro potency of the test compounds to compete ... |
|
| Determination of Partition Coefficients for Trichloroethanol (TCOH) and Chloral Hydrate (CH)-Two Metabolites of Trichloroethylene (TCE) |
FEB 1995 |
15 pages |
| Authors:
C. Seckel; J. R. Creech; R. K. Black; B. L. Garrity; MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
|
| Trichioroethylene (TCE), a common groundwater contaminant, has been shown to be carcinogenic in some animal species. To determine the risk in humans, the use of physiologically-based pharmacokinetic models (PBPK) has become increasingly the method of choice. Formerly it was a common practice to calculate risk estimates on the basis of administered dose-toxicity/tumor incidence, it is now recognized that the dose delivered to the target organ is more accurate. Determination of ... |
|
| Analysis of Investigational Drugs in Biological Fluids - Method Development and Routine Assay |
14 AUG 94 |
309 pages |
| Authors:
Emil T. Lin; CALIFORNIA UNIV SAN FRANCISCO SCHOOL OF PHARMACY
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| Work on development and/or validation of analytical methodologies during the first half of the contract focused on assays for WR 238,605, halofantrine (and its metabolite), WR 6026 (and its metabolites), mefloquine (and its metabolite), artelinic acid, p-aminoheptanophenone (and related compounds), and primaquine (and its metabolite). Work on routine analyses of biological specimens during this period was performed for studies that required determination of concentrations of WR 238,605, halofantrine (and its ... |
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| The Mechanisms and Effects Off the Plant-Activations of Chemicals in the Environment |
20 DEC 93 |
23 pages |
| Authors:
Michael J. Plewa; ILLINOIS UNIV AT URBANA INST FOR ENVIRONMENTAL STUDIES
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| Plants can activate promutagens into stable mutagens and these genotoxic agents may be hazardous to the environment and to the public health. Plant systems have been widely employed in classical and environmental mutagenesis. However, the environmental and human health impact of plants exposed to environmental xenobiotics were not well recognized until the presence of pesticide contaminants in food supplies caused alarm. The capability of plants to bioconcentrate environmental agents and ... |
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| Synthesis and Antimuscarinic Activity of 2-(N-(Ethyl)-(N-Beta- Hydroxyethyl)) Aminoethyl 2,2-Diphenylpropionate, a Metabolite of Aprophen |
JUN 1993 |
4 pages |
| Authors:
Nesbitt D. Brown; Haim Leader; Lawrence R. Phillips; Ruthann M. Smejkal; Richard K. Gordon; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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| The preparation of 2-(N-(ethyl)-(N-beta-hydroxyethyl)aminoethyl 2,2- diphenylpropionate (1), a metabolite of aprophen 12-diethylaminoethyl 2,2- diphenylpropionate) is described. Hydrolysis of 2-(2-chloroethyl) ethylaminolethyl acetate hydrochloride (2) In a basic solution, followed by acidic pH adjustment, gave the ethylcholineaziridinium ion (3) that upon treatment with 2,2-diphenylpropionic acid produced 1 in a 56% yield. Synthetic 1 was found to possess antimuscarinic activities, but was approx. 10-fold less potent than the parent compound aprophen. |
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| Verification of Lewisite Exposure: Quantification of Chlorovinylarsonous Acid in Biological Samples. |
13 MAY 1993 |
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| Authors:
Edward M. Jakubowski; J. R. Smith; T. P. Logan; N. Wiltshire; C. L. Woodward; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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 | Lewisite (dichloro-2-chlorovinylarsine) is a chemical warfare vesicant which causes immediate pain and systemic arsenic poisoning. Under alkaline conditions, lewisite is rapidly converted to acetylene, chloride ion, and arsenic trioxide. These products can be monitored but are not necessarily specific for lewisite's. In our opinion, a better marker of exposure can be found in lewisites acidic hydrolysis products which are chlorovinyl arsonous acid (CVAA) and HC1. CVAA preserves most of lewisite's ... |
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| Quantitative Structure-Activity Relationships of Chlorinated Alicyclic Compounds |
31 JAN 93 |
13 pages |
| Authors:
Janice E. Chambers; MISSISSIPPI STATE UNIV MISSISSIPPI STATE COLL OF VETERINARY MEDICINE
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| The project, which was designed to conduct a quantitative structure- activity relationship study on a series of chlorinated alicyclic compounds (a number of which are insecticides or their metabolites or degradation products) was initiated, with the neurochemical characterization being conducted at Mississippi State University and the physicochemical characterization being conducted at Iowa State University. Experiments quantified the inhibitory potency of the compounds for the binding of 35S-t-butylbicyclophosphorothionate (TBPS), which binds ... |
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| Storage Stability of pCTFE Carboxylic Acid Metabolites |
OCT 92 |
29 pages |
| Authors:
W. T. Brashear; R. J. Greene; D. L. Pollard; MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
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| Studies conducted at the Toxic Hazard Research Unit have analyzed trimer and tetramer carboxylic acid metabolites of polychlorotrifluoroethylene (pCTFE) in biological samples. Tissue samples have been stored at -70 deg C, and urine and feces have been stored at -20 deg C for periods of time ranging from several months to over 1 year. At the time of these analyses, the storage stability of the carboxylic acid metabolites of pCTFE ... |
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| Metabolite Identification of Halon Replacement Compounds |
JUN 92 |
38 pages |
| Authors:
W. T. Brashear; M. M. Ketcha; D. L. Pollard; C. S. Godin; H. F. Leahy; MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
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| Halon 121 1 is currently being used by the U.S. Air Force as a flight line fire extinguishant. Because of health and environmental concerns over ozone depletion, Halon 1211 must be phased out by the year 2000. Before all interim replacement can be chosen, the toxicity of prospective candidates needs to be evaluated. This study has investigated the metabolism of the Halon replacement candidates perfluorohexane (PFH) and the hydrochlorofluorocarbons (HCFCs): ... |
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