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  • Articles: DFG German National Licenses  (12)
  • 1995-1999  (12)
  • Life and Medical Sciences  (5)
  • ALCOHOL  (3)
  • Dopamine  (2)
  • General Chemistry  (2)
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  • Articles: DFG German National Licenses  (12)
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  • 1
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Microdialysis ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0–2.0 mg/kg IP) or PHEN (1.0–2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3–10.0 mg/kg IP), amphetamine (0.1–3.0 mg/kg IP) and nicotine (0.1–0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.
    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
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 64 (1997), S. 390-402 
    ISSN: 0730-2312
    Keywords: carboxy-terminal repeat domain (CTD) ; RNA polymerase II ; cyclin-dependent kinases ; phosphorylation ; transcription ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cdc2 kinase triggers the entry of mammalian cells into mitosis, the only cell cycle phase in which transcription is globally repressed. We show here that Cdc2 kinase phosphorylates components of the RNA polymerase II transcription machinery including the RNA polymerase II carboxy-terminal repeat domain (CTD). To test specifically the effect of CTD phosphorylation by Cdc2 kinase, we used a yeast in vitro transcription extract that is dependent on exogenous RNA polymerase II that contains a CTD. Phosphorylation was carried out using immobilized Cdc2 so that the kinase could be removed from the phosphorylated polymerase. ATPγS and Cdc2 kinase were used to produce an RNA polymerase 110 that was not detectably dephosphorylated in the transcription extract. RNA polymerase 110 produced in this way was defective in promoter-dependent transcription, suggesting that phosphorylation of the CTD by Cdc2 kinase can mediate transcription repression during mitosis. In addition, we show that phosphorylation of pol II with the human TFIIH-associated kinase Cdk7 also decreases transcription activity despite a different pattern of CTD phosphorylation by this kinase. These results extend previous findings that RNA polymerase 110 is defective in preinitiation complex formation. Here we demonstrate that phosphorylation of the CTD by cyclin-dependent kinases with different phosphoryl acceptor specificities can inhibit transcription in a CTD-dependent transcription system. J. Cell. Biochem. 64:390-402. © 1997 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 7
    ISSN: 0044-8249
    Keywords: Cer ; Lanthanoide ; Polyoxometallate ; Supramolekulare Chemie ; Wolfram ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 165 (1995), S. 367-375 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The expression of the 72 kD inducible heat shock protein (hsp72) has been reported to be cell cycle associated in unheated, synchronized HeLa cells. In this study, flow cytomerty was used to investigate hsp72 levels through the cell cycle in HeLa cells by dual labeling with propidium iodide and antibodies against hsp72. The entire cell cycle distribution of hsp72 could be measured in a single sample of asynchronously growing cells. For unheated cells, the level of hsp72 increased about 30% from G1 to S phase, with about a 65% increase in G2/M, probably due to cell size differences. Neither mitotic selection nor serum stimulation induced a higher level of hsp72 than in the control cells. Western blot analysis of hsp72 from Hoechst-stained cells sorted from G1, mid-S, or G2/M showed that G1 cells had the lowest level of hsp72, with about a 30% increase in S phase and a 60% increase in G2/M, in good agreement with the flow cytometry results. These data conflict with previous reporty by other laboratories which showed a 3-fold higher level of hsp72 in S phase than in G1 or G2. In contrast, heat shock (both acute and chronic) led to a non-uniform increase in hsp72 through the cell cycle. Most cells in mid S phase had high levels of hsp72, and a larger range in the levels of hsp72 were found in G1 and late S/G2/M phase cells. © 1995 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 164 (1995), S. 491-498 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: RNA blots of total cellular RNA isolated from quiescent and endothelin (ET-1)-stimulated normal rat kidney (NRK) cells demonstrated that ET-1 induced the expression of c-jun, jun B, and c-fos mRNA in a time-dependent manner with maximal expression of mRNA by 1 hr after the addition of ET-1. Five hundred picomolal ET-1 was sufficient to induce maximal mRNA expression. These data agreed with saturation experiments which demonstrated that maximal binding of [125I]ET-1 was achieved at concentrations greater than 100 pM. The Kd and Bmax values for [125I]ET-1 binding to NRK membranes were 20.5 pM and 22.2 fmol/mg protein, respectively. Competition experiments for the binding of [125I]ET-1 to NRK membranes demonstrated that ET-1 was a more potent inhibitor (Ki = 0.047 nM) than ET-3 (Ki = 10.8 nM). No specific binding of [125I]ET-3 (40 or 500 pM) to NRK membranes could be observed. The expression of c-jun, jun B, and c-fos mRNA was inhibited by the endothelin type A receptor (ET)-selective antagonist, BQ-123. Thus, these data demonstrate that ET-1 mediates the expression of immediate response gene mRNA in NRK cells via the ETA receptor. ET-1 stimulation of NRK cells also upregulated EGF receptors, providing a possible mechanism for ET-1 complementation of epidermal growth factor (EGF) mitogenicity in NRK cells. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 19 (1998), S. 1-19 
    ISSN: 0197-8462
    Keywords: RF fields ; nonthermal ; biological effects ; research agenda ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments.It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated.Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups.Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1-19, 1998. © 1998 Wiley-Liss, Inc.
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