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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 44 (1999), S. 1349-1355 
    ISSN: 1573-2568
    Keywords: ANTITHROMBIN III ; THROMBIN ; HEPARIN ; BLOOD COAGULATION ; ACETALDEHYDE ; ALCOHOL ; ALCOHOLISM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acetaldehyde (AcH) at preincubationconcentrations of 447, 89.4, and 17.9 mM potentiates theeffects of heparin on the clotting time of plasma. Whilecontrol plasma clotted in the range of 12.6 ± 0.1 to 13.8 ± 0.1 sec, and heparin-treatedplasma clotted in a range from 131.5 ± 2.5 to168.2 ± 1.2 sec, heparin that was preincubated atroom temperature for 30 min with 89.4 or 447 mM AcH didnot clot plasma in 300 sec. Heparin exposed to 17.9 mMAcH clotted plasma in 193 ± 1.1 sec. Ethanol ata 404 mM concentration also prolonged the clotting timeof heparin-treated plasma 〉300 sec, while 202 mM ethanol prolonged the clotting time ofheparin-treated plasma from 149.0 ± 2.0 sec to219.5 ± 1.7 sec. It is suggested that AcH altersthe tertiary structure of heparin by adduct formation,possibly by formation of cyclic acetals with iduronicand glucuronic acids, thereby more readily affectingbinding of the glycosaminoglycan to antithrombin IIIand/or thrombin, prolonging clotting time. Ethanol, which does not react covalently with heparin,might affect its conformation as a consequence of anorganic solvent effect. Protamine sulfate prolonged theclotting time of plasma from 13.6 ± 0.1 sec to 17.9 ± 0.2 sec. Protaminesulfate-treated heparin clotted plasma in 21.0 ±0.4 sec relative to heparin-treated plasma (160.4± 1.7 sec). In subsequent experiments,AcH-treated protamine sulfate extended the clotting time of protamine sulfate from17.9 ± 0 sec to 33.7 ± 0.6 sec. Prioraddition of protamine sulfate to AcH- heparin mixturesor heparin to protamine sulfate-AcH mixtures beforeaddition to plasma resulted in clotting times of 22.0± 0.4 sec and 24.1 ± 0.5 sec,respectively, relative to control clotting times of162.3 ± 2.6 sec for plasma-heparin mixtures.These results confirm both the reduction in coagulation time ofheparin-treated plasma by protamine sulfate and theprolongation of clotting time of plasma by protaminesulfate. Furthermore, and importantly, they indicatethat acetaldehyde-treated protamine sulfate is a more effectiveanticoagulant than protamine sulfate. It is suggestedthat reversible adduct formation between acetaldehyde,heparin, and protamine sulfate may occur as a meansexplaining the essentially identical coagulation time ofthese mixtures when added to plasma regardless of theorder of premixing. Ethanol (404 mM) did not influenceprotamine sulfate effects. Lastly, the potentiation of the anticoagulant function of heparin byacetaldehyde suggests that a structural modification ofthe glycosaminoglycan may occur in alcoholics.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2568
    Keywords: ALCOHOL ; COAGULATION ; FACTOR VII ; FACTOR IX ; ACETALDEHYDE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The first metabolite of ethanol, acetaldehyde,has the ability to form adducts with proteins and altertheir function. It has been shown that acetaldehydereacts with various proteins of the blood coagulation pathway and, subsequently, produces aprolongation of the clotting time. This study evaluatedthe function of clotting proteins from the extrinsiccoagulation pathway (factor VII) and the intrinsiccoagulation pathway (factor IX) when preincubated withacetaldehyde as compared to a control and compared topreincubation with ethanol. Prior to use in a clottingassay, incubation times with acetaldehyde, ethanol, and the control were the same for both factorsVII and IX. An automatic fibrometer measured theclotting times. Factor VII preincubated withacetaldehyde prolonged the clotting time. However,factor IX preincubated with acetaldehyde actuallydecreased the clotting time. Of interest, both factorsVII and IX preincubated with acetaldehyde producedstatistically significant results when compared to thecontrol and ethanol. This experiment indicates thatacetaldehyde, in forming an adduct with proteins of theblood coagulation pathway, may induce a conformationalchange of factors VII and IX so as to either increase or decrease the clotting time. Therefore, it ispossible that some of the deranged coagulation inalcohol abusers may be a final net result of theinteraction of acetaldehyde and proteins of thecoagulation pathway.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 43 (1998), S. 1746-1751 
    ISSN: 1573-2568
    Keywords: ANTITHROMBIN III ; THROMBIN ; ACETALDEHYDE ; ALCOHOL ; ALCOHOLISM ; BLOOD COAGULATION
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anticoagulant activity of antithrombin III(ATIII), as observed in a plasma-free system consistingof thrombin and fibrinogen, is readily reduced byacetaldehyde (AcH) at concentrations of 447, 89.4, and 17.9 mM. Whereas controlthrombin-fibrinogen mixtures clotted in 17.7 ±0.75 sec, ATIII prolonged clotting time to 55.0 ±1.75 sec on preincubation with thrombin for 30 min atroom temperature. On subsequent preincubation of ATIII with theAcH for 30 min at room temperature and passage of themixture through Sephadex G-25 minicolumns to removeexcess AcH, the eluates were tested for anticoagulant activity. Clotting times of 20.9 ± 1.0,32.3 ± 1.0, and 45.3 ± 1.6 sec wereobtained with 447, 89.4, and 17.9 mM AcH-ATIII mixtures,respectively. These data suggest that functional groupson ATIII, such as guanidiniums, aminos, and others aresusceptible to adduct formation with AcH, therebyaltering the shape and charge of the anticoagulant. Asa consequence of this type of reaction, an alteredmolecule of reduced biological activity may be produced.These experimental results may explain, in part, thereduction in ATIII levels reported by others in patientswith alcoholic liver disease.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 6 (1979), S. 187-190 
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Quantification of low levels of psychotropic drugs (10-7 to 10-9 g ml-1) in small volumes of plasma requires sensitive and accurate methods. Validation of these methods is best achieved by comparing results obtained using several techniques. In this study, amphetamine levels in plasma were measured using gas chromatography mass spectrometry and radioimmunoassay. Correlation of the results obtained by the two methods was found to be positive and high (R = 0.9822). The average coefficient of variation between assays for gas chromatography mass spectrometry was 5.8% and for radioimmunoassay was 12.3%, while the average coefficient of variation within assays for gas chromatography mass spectrometry was 4.9% and for radioimmunoassay 6.9%. Although gas chromatography mass spectrometry was 1.9 times more sensitive than radioimmunoassay, for most purposes, the convenience of the radioimmunoassay method outweighs the technical superiority of gas chromatography mass spectrometry.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Metabolism of 1,1,1,2,2-pentafluorohexane with liver microsomes from phenobarbital-treated rats gave only one metabolite, namely, the 5-hydroxy derivative. Under similar conditions 1,1-difluorocyclohexane was metabolized to give mainly the 3- and 4-hydroxy derivatives in the ratio 1:∼5.5 The structures of these metabolites were established by chemical ionization (CI) and/or electron impact (EI) mass spectrometry and confirmed by synthesis in the case of 1,1-difluorocyclohexan-4-ol. Oxidation of 1,1-difluorocyclohexane with lead tetrakis(trifluoroacetate) also gave, inter alia, the 3- and 4-hydroxy derivatives. In saturated hydrocarbons complete replacement of hydrogen by fluorine at one particular carbon will not only block microsomal hydroxylation thereat but will also inhibit hydroxylation at neighbouring hydrogen-bearing carbons, (α almost completely, β markedly, γ slightly).
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 16 (1988), S. 211-213 
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The use of octafluorotoluene (OFT) as a versatile gas chromatographic/mass spectrometric derivatizing agent for steroids containing alcoholic, phenolic or α,β-unsaturated keto functions, is described. Two distinct derivatizing schemes can be utilized, involving (method 1) a phase-transfer reaction, employing a two-phase system of CH2Cl2 and N NaOH with n-Bu4NHSO4 as catalyst (suitable for alcoholic and phenolic steroids) and (method 2) a reaction conducted in anhydrous dimethylformamide at 155°C with CsF as base (appropriate for α,β-unsaturated keto steroids). Perfluorotolyl (PFT) ethers and/or enol ethers have thus been generated. The electron impact spectra display abundant high-mass molecular ions where derivatization has occurred at a phenolic or enolic function. An extraction, derivatization and gas chromatographic/mass spectrometric scheme has been devised involving method 2 for the analysis of steroids in human plasma. A preliminary quantitative investigation of the levels of testosterone in plasma has been carried out employing these methods. The anomalously high level found is explained in terms of the presence in plasma of lipid-soluble derivatives of testosterone (probably fatty acid esters) which generate the testosterone bis-OFT derivative under the reaction conditions employed.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method using particle beam liquid chromatography/mass spectrometry was developed for the confirmation of oxytetracycline, tetracycline and chlortetracycline residues in bovine milk. This method is one of the first to apply particle beam technology to the confirmation of animal drug residues in food products for regulatory purposes. The milk is centrifuged, using molecular weight cut-off filters to remove components of 25 000 daltons and above from the milk. The filtrate is passed through a C-18 sample preparation cartridge which retains the tetracyclines. After the columns are washed with water, the tetracyclines are eluted with 0.1 M oxalic acid in methanol and concentrated. The compounds are separated on a Novapak C-18 column with a methanol-oxalic acid-acetonitrile mobile phase. Negative chemical ionization with selective ion monitoring is used to identify the tetracyclines. The procedure was used to confirm the presence of each tetracycline at 100 ng ml-1 in fortified and incurred milk samples.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Mass spectra of mercapturic acid conjugates of two xenobiotic products of lipid peroxidation (trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal) as well as conjugates of 1,3-dichloropropene, styrene oxide, 1,2-naphthalene oxide and α-chlorotoluene were obtained using fast atom bombardment or negative chemical ionization. Fragmentation pathways were investigated using linked scan and mass-analyzed ion kinetic energy spectrometric techniques. Characteristics of the spectra obtained using different ionization and sample introduction techniques are compared. Deprotonated molecular ions of mercapturic acids gave simple daughter ion spectra, with the dominant mode of decomposition involving cleavage of C—S bonds giving a characteristic neutral loss of 129 Da Screening for mercapturates in urine samples was performed using neutral loss scanning and yielded limits of detection in the low nanogram per milliliter range. Quantitative analysis of the S-benzyl mercapturic acid at 1 p.p.b. in urine has been demonstrated using combined gas chromatography/electron capture mass spectrometry with d3-S-benzyl mercapturic acid as internal standard.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 8 (1981), S. 503-505 
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three physiologically important disaturated lecithins have been analyzed quantitatively as the acetate derivatives using a solids inlet probe and ammonia chemical ionization. Concentration independent response factors have been determined over a tenfold range that brackets human plasma levels. The results obtained serve as an independent corroboration of gas chromatographic analyses.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0269-3879
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The application of reductive coulometric electrochemical detection for analysis of the monoamine neurotransmitters norepinephrine, dopamine, and serotonin and their common metabolites in brain and cerebrospinal fluid following separation by isocratic high performance liquid chromatography is described. The high sensitivity and screening capabilities of coulometric electrodes permits the accurate quantitation of as little as 3-5 pg of these compounds in tissue following a simple single step purification procedure. Moreover, comparison of peak height ratios obtained from analysis of authentic reference standards and tissue samples at selected multiple electrode potentials provides a straightforward means for qualitative evaluation of peak identification and purity during analysis of biological samples. The method is comparatively inexpensive and precise within and between day coefficients of variation for most compounds range from 2-5%. Thirty samples can be run in duplicate in a 24 h period.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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