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  • thermogenesis  (3)
  • 6-mercaptopurine  (1)
  • Springer  (4)
  • Copernicus
  • American Meteorological Society (AMS)
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Publisher
  • Springer  (4)
  • Copernicus
  • American Meteorological Society (AMS)
Years
  • 1
    ISSN: 1432-1041
    Keywords: azathioprine ; 6-thiouric acid ; 6-mercaptopurine ; renal transplantation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (6-TU) and 6-mercaptopurine (6-MP), metabolites of AZA, may provide more readily measurable indices of the pharmacologic activity of AZA. In order to evaluate the utility of 6-TU and 6-MP plasma concentrations in monitoring AZA therapy, we studied their pharmacokinetics in 6 renal transplant patients, and their in vitro immunosuppressive potency in a mixed lymphocyte proliferation assay. A peak plasma 6-TU concentration of 710.7 ng/ml was observed at 3.8 h after oral dosing. Good correlation was observed between the elimination t1/2 of 6-TU and serum creatinine, and between AUC over 24 h and serum creatinine. However, we did not observe a second peak in plasma 6-TU concentration that could be attributed to the degradation of active AZA metabolites. 6-MP plasma concentrations in the patients were low (mean peak concentration 36.0 ng/ml) and rapidly disappeared within 8 h. In vitro immunosuppressive activity could not be demonstrated for 6-TU over a concentration range of 1.25 ng/ml to 0.25 mg/ml. We conclude that 6-TU is pharmacologically inert and is primarily eliminated by the kidneys. Our findings currently do not support the use of plasma concentrations of 6-TU or 6-MP to monitor AZA therapy. In order to optimize AZA therapy, analytical techniques that are technically feasible and that can directly quantify the active intracellular thiopurines are being explored.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 44 (1988), S. 40-42 
    ISSN: 1420-9071
    Keywords: TRH ; TRH analogues ; thermogenesis ; brown adipose tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Acute or chronic injection of RX 77368 (a TRH analogue; 1 mg/kg s.c.) stimulated oxygen consumption (VO2) and brown adipose tissue activity in the rat, and decreased weight gain Other TRH analogues (CG 3509, RGH 2202) and TRH itself also stimulated VO2. These thermogenic actions are probably mediated centrally by stimulation of sympathetic outflow to brown fat.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-4935
    Keywords: tumour necrosing factor ; brown fat ; thermogenesis ; GDP-binding ; food intake ; body weight ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A single intravenous injection of recombinant human tumour necrosis factor (TNF) resulted in significant, but transient (24–48 hr) reductions in food intake and body weight, and increases in rectal temperature, resting oxygen consumption (VO2) and brown adipose tissue (BAT) thermogenic activity (mitochondrial GDP-binding). The increased VO2 was inhibited by β-adrenergic blockade (propranolol), and activation of BAT was prevented by denervation of the tissue. In adult (4-month old) animals, TNF induced greater reductions in food intake and body weight, caused general malaise and some fatalities, but did not significantly alter VO2 or BAT activity. However, the reduction in VO2 following β-adrenergic blockade was greater in TNF-treated rats and BAT activity was enhanced when compared to pair-fed controls. Injection of adult rats with gamma-interferon induced small changes in body weight and temperature which were slightly potentiated when injected with a low dose of TNF. The results indicate that TNF stimulates sympathetic outflow to BAT. This effect may be partly responsible for the increases in body temperature and metabolic rate associated with TNF treatment and with cancer cachexia.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 6 (1986), S. 3-18 
    ISSN: 1573-4935
    Keywords: brown adipose tissue ; thermogenesis ; cold ; diet ; neural control ; hormonal control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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