Two studies were conducted to determine whether sodium thiosulfate (THS) can estimate extracellular water (ECW) in beef cattle in conjunction with empty body water (EBW) estimation by urea space. ...Experiment 1 used 24 steers (366 kg) to determine the clearance parameters for THS and urea. Blood samples were taken over 1 h. A two-component curve, Y = A1ek1(t) + A2ek2(t), (t = hours after infusion) fit the clearance of both markers; intercepts (Al, A2) and clearance coefficients (k1, k2) were 44.8, 44.4, -25.8, and -2.24 mg/dL, respectively, for THS (r2 = 0.98, Sy.x = 2.72), animal effects removed and 24.4, 10.5, -21.7, and -.71 mg/dL, respectively, for urea (r2 = 0.98, Sy.x = 1.49). Sodium thiosulfate equilibrated with ECW 5 to 10 min after infusion. Experiment 2 consisted of 22 steers (483 kg) infused with a combination solution of 20% urea, 10% THS, and 4% sodium thiocyanate (SCN; equilibration time = 28 min); half the steers were implanted with estradiol. Empty body water increased with implantation (P 0.01). Extracellular water tended to increase in implanted steers as measured by THS (12 min, P 0.2) from the SCN estimate at 28 min (SCN = 3.7 + 0.873 THS; r2 = 0.70; P 0.001). Sodium thiosulfate gave reasonable estimates of ECW (22 to 26% of BW) and required only 0- and 12-min blood samples. The results indicate that EBW and ECW can be estimated simultaneously using two markers and, by difference, can provide an estimate of intracellular water and lean body mass
Background and Purpose: Several clinical studies have suggested that the combination of radiation therapy and 5-fluorouracil (5-FU) may improve outcome of patients with pancreatic cancer. However, ...there are few experimental studies supporting this treatment. Aim of the Study: To examine the radiosensitivity of human pancreatic cancer cells and its modulation by 5-FU. Material and Methods: MiaPaCa-2, PANC-1 and NP-18 cells growing as monolayer culture were treated with radiation and 5-FU. In addition, 5-FU was studied administered either pre- or postradiation, both as pulse or continuous exposure. Cell survival was determined by the in vitro clonogenic assay. Results: In MiaPaCa-2 cell line, both radiation and 5-FU alone reduced cell survival. The addition of 5-FU to radiation caused a significant net decrease of cell survival. Pulse exposure of 5-FU decreased survival after 2 Gy and mean inactivation dose by 1.64; continuous exposure decreased survival after 2 Gy and mean inactivation dose by about 2.4. Timing of 5-FU exposure did not modify survival. However, when adjusting for 5-FU killing effect and cell multiplicity, only continuous exposure significantly enhanced radiation cell killing. Conclusion: Both pulse and continuous exposure increase radiation cell killing, but only continuous exposure may radiosensitize MiaPaCa-2 cells.
The degree of interindividual and intraindividual variability in acetylator activity was investigated with caffeine used as a probe of enzyme activity. Acetylator phenotype and relative ...N‐acetyltransferase activity were estimated in 46 subjects by measuring the urinary ratio of two metabolites, AFMU/1‐MX, after a single 300 mg oral dose of caffeine on five separate occasions. Thirty homozygous slow (rr) and 15 heterozygous rapid (Rr) acetylators were identified. The degree of interindividual variability in acetylator activity was observed to be a mean of 32% (range 27% to 36%) and 20% (range 11% to 29%) in the rr and Rr groups, respectively. The mean intraindividual variation on repetitive measurement was 19% (range 6% to 49%) in the rr and 14% (range 7% to 24%) in the Rr acetylator group. Four subjects had apparent changes in acetylator activity with time such that they were unable to be assigned to any one acetylator group. Two of these four subjects exhibited apparent homozygous rapid acetylator activity intermittently during the 5‐week trial. This variability may explain, in part, some of the high degree of patient variability observed in the toxicity, efficacy, and drug‐related disease associated with acetylated drugs and environmental toxins.
Clinical Pharmacology and Therapeutics (1988) 44, 152–157; doi:10.1038/clpt.1988.130
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