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  • 1
    Book
    Book
    Synchronization : a universal concept in nonlinear science; 12 (2003)
    Cambridge :Cambridge Univ. Press,
    Details
    Title: Synchronization : a universal concept in nonlinear science; 12
    Author: Pikovskij, Arkadij S.
    Contributer: Rosenblum, Michael G. , Kurths, Jürgen
    Edition: 1. pbk. ed.
    Publisher: Cambridge :Cambridge Univ. Press,
    Year of publication: 2003
    Pages: XIX, 411 S. : Ill., graph. Darst.
    Series Statement: Cambridge nonlinear science series 12
    ISBN: 0-521-53352-X , 0-521-59285-2
    Type of Medium: Book
    Language: English
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    Zuse Institute Berlin get availability status
  • 2
    Electronic Resource
    Electronic Resource
    Disposition and metabolism of thiopurines (1981)
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 131-136 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anticancer agent β-2′ deoxythioguanosine (β-TGdR, NSC-71261) has potential utility for the treatment of hematologic tumors resistant to 6-thioguanine (TG). We have studied the pharmacology and metabolism of these two agents in the beagle dog. [35S]β-TGdR was administered as an IV bolus to five dogs at a dose of 10 mg/kg. Plasma radioactivity declined biphasically with an average terminal t1/2 of 3.7 h. Cumulative urinary excretion of the radiolabel 5 h after administration was 19% of the total dose. In another four dogs that received 100 mg/kg (2.71 g), the average terminal plasma t1/2 was 7.7 h and the 5-h cumulative urinary excretion was 28% of the total dose. [35S] Thioguanine, 5 mg/kg was similarly administered IV to three beagle dogs. The average terminal t1/2 of [35S] TG and metabolites was 4.6 h, and the 5-h cumulative urinary excretion of the [35S] label was 47%. Similar studies were conducted in three beagle dogs that received the same dose of [814C] TG. In these studies, however, the terminal phase t1/2 of 14C in plasma was 1.9 h. Cumulative urinary excretion of the 14C was 40% in 5 h. Both TG and β-TGdR were rapidly and extensively degraded. Neither of these agents and none of their metabolites was found in the cerebrospinal fluid in significant concentrations. In the dog, β-TGdR was rapidly metabolized to TG and may serve as a slow release from of TG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00262330
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Comparative cytotoxicity and pharmacokinetics of antimelanoma immunotoxins containing either natural or recombinant gelonin (1999)
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. 343-348 
    Details
    ISSN: 1432-0843
    Keywords: Key words Immunotoxins ; Gelonin ; Melanoma ; Recombinant toxins ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunotoxins are a class of targeted therapeutic agents under development by various research groups. The murine monoclonal antibody designated ZME-018 recognizes a high molecular weight glycoprotein present on most human melanoma cells and biopsy specimens and has been utilized for clinical imaging studies in patients with melanoma. The plant toxin gelonin is a ribosome-inactivating protein (RIP) with n-glycosidase activity similar to that of ricin A chain. In previous studies by our group, the gelonin toxin was sequenced, cloned and expressed in E. coli. The purified recombinant gelonin (RG) was found to have identical protein synthesis inhibitory activity to that of natural gelonin (NG). For comparative purposes, chemical conjugates of antibody ZME and either RG or NG were produced using the heterobifunctional crosslinking reagents SPDP and SMPT. The ZME-NG and ZME-RG immunotoxins were found to be 104- to 105-fold more cytotoxic to antigen-positive human melanoma cells than free toxin. NG toxin alone was cytotoxic to intact cells (IC50 = 100 nM) while RG was nontoxic to cells at doses up to 1 μM. Both ZME-NG and ZME-RG immunoconjugates were nontoxic to antigen-negative (Me-180) cells. ZME-RG immunotoxins constructed with the more stable SMPT reagent were slightly more effective in culture than conjugates made with SPDP. Tissue distribution studies in tumor-bearing nude mice demonstrated that tumor uptake of the ZME-RG immunotoxin was similar to that of the intact ZME antibody with reduced distribution to normal organs compared to an immunoconjugate produced with NG. Pharmacokinetic studies showed that the terminal-phase plasma half-life of ZME-RG was similar to that of ZME itself (42 h vs 50 h) and almost threefold higher than that of ZME-NG (11.5 h). The area under the concentration curve (Cxt) for ZME-RG was 50% lower than that for ZME due to an increased apparent volume of distribution (Vda) but was almost tenfold higher than the Cxt for ZME-NG. These studies suggest that immunoconjugates comprising RG demonstrate identical in vitro cytotoxic effects to immunoconjugates produced with NG and immunotoxins with RG display improved in vivo pharmacodynamics and tissue distribution compared to immunotoxins containing NG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050987
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of endotoxin on the pharmacology of antineoplastic agents (1981)
    Springer
    Cancer chemotherapy and pharmacology 5 (1981), S. 227-231 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Patients with cancer often develop serious gram-negative bacterial infections. Since bacterial endotoxins have been shown to affect the in vitro hepatic metabolism of antineoplastic agents, significant infection may adversely affect drug pharmacokinetics and metabolism in these patients. To evaluate the clinical significance of these effects, bacterial endotoxin (0.5 mg/kg, IV) was administered to male beagle dogs 1 or 24 h prior to the administration of radiolabeled 5-fluorouracil (5-FU), methotrexate (MTX), arabinosylcytosine (Ara-C), or vinblastine (VLB) as an IV bolus. Drug levels in plasma and urine were measured at various times after administration and standard pharmacokinetic parameters were calculated. The pharmacokinetics of all four agents were found to be significantly altered by the administration of bacterial endotoxin. However, there were no detectable patterns to these changes so that no predictions could be made. In studies on rats, chronic, nonlethal endotoxin administration (0.8 mg · kg-1 · day-1 for 10 days) resulted in a dramatic decrease in the distribution of [14C]methylglyoxal bis(guanylhydrazone) (MGBG) in liver, kidney, intestine, heart and lung tissue. This suggests that bacterial endotoxin may also affect drug pharmacokinetics by altering drug penetration into various organs. In studies on hepatic microsomes isolated from rats, bacterial endotoxin incubation affected aniline hydroxylase activity only at concentrations greater than 0.4 mg/ml, at least tenfold higher than the LD50 of endotoxin in rats. It therefore seems likely that the endotoxin may require in vivo metabolism to affect changes in drug metabolism and disposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00434389
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man (1982)
    Springer
    Cancer chemotherapy and pharmacology 8 (1982), S. 119-123 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, β-2′-deoxythioguanosine (β-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of β-TGdR in patients with cancer after intravenous administration. [35S]-β-TGdR (5.4 mg/kg, 200 mg/m2, 200 μCi total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t1/2) of 14 min and a terminal t1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [35S]-6-TG (3.4 mg/kg, 125 mg/m2, 200 μCi total) the average initial t1/2 was 40 min while the terminal phase t1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that β-TGdR is merely a latent form of TG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00292882
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Modification of methyliminodiacetato-trans-R, R-1,2-diamminocyclohexane platinum(II) pharmacology using a platinum-specific monoclonal antibody (1990)
    Springer
    Cancer chemotherapy and pharmacology 25 (1990), S. 405-410 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Platinum complexes are extremely active chemotherapeutic agents. A murine monoclonal antibody designated 1C1 was developed that binds to the thirdgeneration platinum complex methyliminodiacetato-trans-R,R-1,2-diamminocyclohexane platinum(II) (MIDP). Competitive enzyme-linked immunosorbent assay (ELISA) shows that antibody 1C1 binds preferentially to the 1,2-diamminocyclohexane (DACH) side-chain of the platinum complex, although non-DACH-containing platinum complexes can compete for binding at high concentrations. When tested against MCF-7 breast carcinoma cells, the 1C1-MIDP complex caused 50% growth inhibition at 0.63 μg Pt/ml, whereas MIDP alone caused 50% growth inhibition at a concentration of 0.16 μg Pt/ml. Pharmacokinetic studies in rats using [3H]-MIDP showed that the drug was cleared triphasically from plasma, with elimination-phase half-lives (t1/2) of 1.2, 10.2, and 243 min for α, β, and γ phases, respectively. The MIDP-1C1 complex was cleared with longer half-lives of 5, 26, and 291 min, respectively. The overall clearance rate from plasma of the MIDP-1C1 complex was 10-fold lower than that of MIDP alone (0.37 vs 3.01 ml/kgxmin). Tissue concentrations of [3H]-MIDP 3 h after administration showed that 1C1 antibody prevented MIDP distribution to most organs and dramatically reduced [3H] concentration in the intestine, liver, kidney, heart, and skeletal muscles. Studies are under way to determine the relative therapeutic activity of the 1C1 antibody-MIDP complex and assess whether the 1C1 antibody may be useful for antibodydirected delivery of platinum complexes to tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686050
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    Disposition of methylglyoxal bis(guanylhydrazone) (MGBG, NSC-32946) in man (1981)
    Springer
    Cancer chemotherapy and pharmacology 7 (1981), S. 31-35 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A high-pressure liquid chromatographic method was utilized to determine the concentration of the antileukemic agent methylgloxal bis(guanylhydrazone) (MGBG, NSC-32946) in tissue samples obtained at autopsy from patients who received MGBG. In a patient with cholangiocarcinoma who received one course of MGBG (500 mg/m2), the highest drug concentration was found in normal liver tissue. However, the drug concentration in intrahepatic tumor tissue was only 10% of that found in uninvolved liver. In a patient with acute myelogenous leukemia (AML) who received 12 courses of MGBG therapy, highly infiltrated lymph node tissue was found to contain the highest concentration of MGBG. High concentrations of the drug were also found in liver, spleen, kidney, adrenal, and thyroid. The drug penetrated well into normal brain tissue. After repeated administration, high drug concentrations were found in cerebral and cerebellar gray matter. These studies suggest that there is no selective uptake of MGBG into solid tumors early after drug administration and provide a pharmacologic rationale for testing this agent against endocrine and intracerebral tumors in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00258210
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis (1996)
    [s.l.] : Nature Publishing Group
    Nature 383 (1996), S. 323-327 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A random process is stationary if its statistical characteristics are invariant under time shifts, that is, if they remain the same when t is replaced byt + A, where A is arbitrary. The probability densities, together with the moment and correlation functions, do not then depend on the absolute ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/383323a0
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    Paper (German National Licenses)
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  • 9
    Electronic Resource
    Electronic Resource
    Multifractality in human heartbeat dynamics (1999)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 399 (1999), S. 461-465 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] There is evidence that physiological signals under healthy conditions may have a fractal temporal structure. Here we investigate the possibility that time series generated by certain physiological control systems may be members of a special class of complex processes, termed multifractal, which ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/20924
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    Paper (German National Licenses)
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  • 10
    Electronic Resource
    Electronic Resource
    Heartbeat synchronized with ventilation (1998)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 392 (1998), S. 239-240 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] It is widely accepted that cardiac and respiratory rhythms in humans are unsynchronised. However, a newly developed data analysis technique allows any interaction that does occur in even weakly coupled complex systems to be observed. Using this technique, we found long periods of hidden ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/32567
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