Metabolism of the anti-psoriatic agent 5-methoxypsoralen in humans: comparison with rat and dog.

1. Single oral doses of 14C-5-methoxypsoralen (5-MOP) to human subjects (50 mg), rats (1 mg/kg) and dogs (1 mg/kg) were fairly well absorbed but subjected to extensive first-pass metabolism, at least in rat and human. Means of 62, 51 and 40% dose in urine and 31, 38 and 48% dose in faeces, were excreted by humans (during 5 days), rats (3 days) and dogs (1 day), respectively. In dogs, faecal 14C was probably derived, in part, from biliary excreted material. 2. Total 14C in human plasma reached peak concentrations after 2 h (mean 235 ng 5-MOP equivalent/ml) and declined relatively slowly, to about 60% of this value within 24 h. Unchanged 5-MOP was not detected in plasma using h.p.l.c. (< 5 ng/ml). 3. Tissue concentrations of 14C were generally greater in dogs than rats and reached peak levels at 1 h in dogs but at 24 h in rats. Apart from liver and bile, dog tissue 14C concentrations were lower than those in the corresponding plasma, whereas in rat they were lower only until the time of peak concentrations, after which they were generally greater. 4. 5-MOP was extensively metabolized in all three species. The major 14C-components in human and dog urine were glucuronic acid conjugates, mainly of an arylacetic acid and arylalcohols, resulting from initial oxidative metabolism of the furan ring of 5-MOP. In rat, these metabolites were excreted mainly unconjugated. An unusual metabolite was formed by reduction of the lactone moiety of 5-MOP, probably by the gut flora, giving rise to an arylpropionic acid, excreted as a glucuronic acid conjugate in the urine of all three species. 5. Unchanged drug was a very minor component of human and rat plasma, but a major component of dog plasma. In all three species, circulating 14C-metabolites were similar to those in the urine but were present mainly unconjugated. On the basis of these data, the metabolic fate of 5-MOP in humans was more similar to that in dog than to that in rat, although humans appeared to metabolize 5-MOP more rapidly than did dog.     

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

Gd DTPA. Future applications with advanced imaging techniques

In this admittedly preliminary view of the future, the authors present a number of new concepts in MR imaging and consider their possible advantages and limitations.     

A critical appraisal of the anaesthesia literature

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - Today’s anaesthesia journals are faced with problems in the quality of materials being published. The stature of...     

Primary carcinoid tumor of the urinary bladder.

A 62-year-old woman who presented with urinary frequency and microscopic hematuria was found to have a 1.2 x 1.0 x 0.6-cm polypoid carcinoid tumor of the urinary bladder. The tissue resected from the base after removal of the polypoid lesion disclosed a small focus of residual carcinoid tumor, associated with Brunn's epithelial nests, cystitis cystica, and cystitis glandularis. Tumor cells exhibited strong argyrophilia and weak argentaffinity. Immunohistochemical staining reactions were strongly positive for chromogranin and serotonin, and electron microscopy revealed characteristic dense-core granules. Flow cytometric evaluation revealed an aneuploid cell population with a DNA index of 1.20.     

DQ Wa gives rise to a DQβ restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type Of DQw3

DQ beta restriction fragment patterns have been obtained from five DRw8 cell lines homozygous for the null DQ allele, DQWa. The enzymes Bgl II, Bam HI and Pvu II generate DQ beta patterns which are indistinguishable from those obtained from cell lines homozygous for DQw3.2.