The ratio of urinary 6beta-hydroxycortisol (6beta-OHF) to free cortisol (F), i.e., the 6beta-OHF/F ratio, has been reported to be a specific marker for human CYP3A induction by in vivo studies of human subjects. In the development of drugs, it is quite beneficial to predict human CYP3A induction in preclinical safety studies using urine samples from experimental animals. We examined the 6beta-OHF/F ratio in urine of common marmosets administered with rifampicin, a potent inducer of CYP3A, to evaluate the usefulness of common marmosets for the prediction of CYP3A induction. Rifampicin was orally administered to three groups of four male common marmosets at doses of 0, 10, and 20 mg/kg per day for 4 days. Amounts of 6beta-OHF and F in urine samples were determined by means of high-performance liquid chromatography (HPLC) during the experimental period. One day after the 4th dosing, animals were killed, and P450 contents and P450-catalyzed. 7-alkoxycoumarin O-dealkylase (ACD) activities in the liver were measured. Western blot analysis of liver microsomes was also performed using anti-rat P450 (CYP1A1, 2B1/2, 3A, and 4A) antibodies. The results indicated elevations in the 6beta-OHF/F ratios that were dependent on both the dosing period and dose levels adopted. The ratios on day 4 reached 4.7- and 5.3-fold the pre-administration values in the 10 and 20 mg/kg per day groups, respectively. P450 contents and ACD activities were also elevated in all of the groups. Western blot analysis showed specific increases in the protein which cross-reacts with anti-rat CYP3A antibody in all of the groups. Furthermore, the 6beta-OHF/F ratio was well correlated with the CYP3A contents in liver (r = 0.906). These results indicated that increase in urinary excretion of 6beta-OHF is a specific marker of the induction of hepatic CYP3A in common marmosets just as in humans. Consequently, the present study suggested that human CYP3A induction elicited by chemical agents can be predicted in common marmosets by measuring the urinary excretion of 6beta-OHF.

7-Alkoxycoumarin O-Dealkylase↗

PubMedDate not supplied

Analysis of human plasma as an exposure level monitor for carcinogenic tryptophan pyrolysis products.

A high-performance liquid chromatography method for detecting 3-amino-1,4- dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in human plasma was developed. Plasma samples of 10 normal subjects were examined. Trp-P-1 and Trp-P-2, carcinogenic tryptophan pyrolysis products, were detected in all specimens, and the concentrations of Trp-P-1 and Trp-P-2 in plasma were 68.31 +/- 24.03 fmoles/ml (mean +/- S.D., n = 10) and 18.79 +/- 4.99 fmoles/ml, respectively. Our results suggest that plasma levels of carcinogenic tryptophan pyrolysis products may be useful indicators for estimating the exposure levels of the dietary carcinogens.

Adult↗

PubMedDate not supplied

[Antero-lateral uncoforaminectomy in treatment of cervical spondylotic monoradiculopathy].

Thirty seven patients with cervical spondylotic monoradiculopathy treated with antero-lateral uncoforaminectomy were analysed. Spondylotic spur of the level associated with radiculopathy was revealed to be continuous from the uncovertebral joint to the posterior ridge of the vertebral body in 35 patients. Antero-lateral uncoforaminectomy was found to safely remove the continuous type of spur, resulting in decompression of the cord-root-complex, which shifted anteriorly after surgery. As a result, no neurological symptoms were observed in 36 of 37 radiculopathy patients. It could be concluded that the most important factor in relieving neurological manifestations of this disorder is decompression of the cord-root-complex.

Adult↗

PubMedDate not supplied

Ultrastructural study of a perineurioma.

A case of soft tissue tumor in the left brachialis muscle of a 49-year-old Japanese female patient was studied by electron microscopy. The tumor was diagnosed as intramuscular myxoma by light microscopy, but electron microscopic observation revealed that the tumor almost entirely consisted of cells similar to normal perineurial cells. The tumor cells possessed long, slender cytoplasmic processes covered by well-developed but discontinuous basal laminae, clusters of pinocytotic vesicles, and infrequent intercellular junctions. Perineurial cells have also been observed in other peripheral nerve lesions: neurofibromas, nerve sheath myxomas, and localized hypertrophic neuropathies. However, the term "perineurioma" or "perineurial cell tumor" should be reserved for discrete tumorous masses that are almost entirely composed of perineurial cells without evidence of residual axons, Schwann cells, fibroblasts, or tactile corpusclelike structures. Perineurioma may represent a third category of peripheral nerve sheath tumors, ultrastructurally distinct from schwannomas and neurofibromas.

Female↗