To evaluate the effects of anaerobic conditions and inducers for the mixed-function oxidase system on the metabolism of mitomycin C, a bioreductive alkylating agent widely used for the treatment of hepatocellular carcinoma, experiments so designed were performed in rats and mice. Metabolism of mitomycin C by microsomes from normal rat liver and diethyl-nitrosamine-induced mouse hepatocellular carcinoma tissue was assessed from the disappearance of the quinone portion of mitomycin C and by measurement of alkylating metabolites using 4-(p-nitrobenzyl)pyridine as a trapping agent. The metabolism of mitomycin C measured by the two independent methods was strikingly increased under anaerobic conditions in both intact and tumor tissues. Since involvement of cytochrome P-450 in the metabolic activation of mitomycin C was shown recently, effects of representative inducers for the mixed-function oxidase system on the metabolism of mitomycin C were also studied. Phenobarbital treatment resulted in a significant increase in the metabolism of mitomycin C in both intact and tumor tissues under anaerobic conditions. The markedly enhanced formation of active metabolites of mitomycin C under anaerobic conditions may explain on a metabolic basis, at least in part, our recent clinical observations that chemoembolizations with microcapsular forms of mitomycin C is more effective than conventional bolus administration of this agent in the treatment of hepatocellular carcinoma. Combination of anaerobic conditions and induction of the mixed-function oxidase system may be applicable to chemotherapy of hepatic malignancy.

Anaerobiosis↗

PubMedDate not supplied

Prognosis of hepatocellular carcinoma smaller than 5 cm in relation to treatment: study of 100 patients.

A total of 100 patients with small hepatocellular carcinoma, less than or equal to 5 cm in diameter, seen during the last 8 years were analyzed retrospectively for survival time in relation to treatment and Child's grading. When analyzed with respect to major treatment modalities without considering stage, the median survival was 35.0 months for 34 patients treated by surgery, 28.8 months for 20 patients treated by transcatheter arterial embolization, 10.6 months for 25 patients treated by intraarterial chemotherapy and 9.7 months for 17 patients who received no specific treatment. When patients were divided into three stages without considering treatment, the median survival was 37.1 months for 37 Child's A patients, 16.2 months for 36 Child's B patients and 1.6 months for 27 Child's C patients. These results suggest that the prognosis depended on treatment given and the Child's grade. The effects of major therapeutic modalities on survival were analyzed with regard to Child's grading. Among Child's A patients, the actuarial survival rate for surgery was better than that for transcatheter arterial embolization and for arterial chemotherapy. Among Child's B patients, the survival rate for transcatheter arterial embolization was better than for other treatments. Among Child's C patients, there was no significant difference in survival rate regardless of treatment and its modality. These results suggest that surgery may be indicated as a first choice in Child's A patients, transcatheter arterial embolization in Child's B patients, and there is no effective treatment in Child's C patients. The major cause of death was hepatic failure irrespective of treatment.

Aged↗

PubMedDate not supplied

Modulation of tryptophan hydroxylase activity in vitro by ethanol depends on biopterin cofactor concentration.

The mechanism of ethanol action at serotonergic neuronal systems in the brain was investigated by examining the effects of alcohols on the activity of tryptophan hydroxylase (TPH) in vitro using natural type of biopterin as cofactor. Alcohols inhibited the activity of TPH prepared from rat brain in a noncompetitive manner with respect to both the biopterin cofactor and the L-tryptophan substrate. The rank order of inhibitory potency of the tested alcohols was n-propanol > iso-propanol > ethanol > methanol. The kinetic study indicated that alcohols more potently affected the enzyme interaction with cofactor than substrate. Ethanol, at concentrations that can be reasonably attained in vivo (i.e., 25-100 mM) significantly decreased TPH activity in the presence of a physiological concentration of cofactor. However, the reduction was only approximately 5% of control activity, because Ki, values of ethanol for the enzyme were very high (800-1000 mM). From the present results, it was concluded that the direct inhibition of the synthetic enzyme itself by ethanol would contribute little to in vivo effects of ethanol on serotonergic neuronal systems.

1-Propanol↗

PubMedDate not supplied

Neurologic sequelae and MRI in low-birth weight patients.

Periventricular hyperintensity was detected using long repetition and echo time on spin-echo magnetic resonance imaging in 24 of 32 children with birth weights less than 2,500 gm. Functionally, 11 children were normal, 6 mildly handicapped, 7 moderately handicapped, and 8 severely handicapped. The functional handicaps were correlated to the degree of periventricular hyperintensity observed on magnetic resonance imaging when periventricular hyperintensity was divided into 4 grades; therefore, the extent of periventricular hyperintensity observed on magnetic resonance imaging has been proved to be of value in the clinical assessment of low-birth weight infants and children and may contribute to the prediction of later functional deficits.

Brain Diseases↗

PubMedDate not supplied

Mechanical properties of osteopenic vertebral bodies monitored by acoustic emission.

A microdamage event, either bone microfracture or microcrack propagation, releases energy. Some of this energy is in the form of acoustic waves. We measured acoustic emission (AE) in normal and osteopenic vertebral bodies during compression loading to confirm the microdamage accumulation. The 2nd to 4th lumbar vertebrae taken from the embalmed cadavers of a 37-year-old male and a 75-year-old female were used. Bone mineral densities (BMDs) were measured by dual energy X-ray absorptiometer (DEXA). The male vertebrae had normal BMDs, while the female vertebrae had lower BMDs than the normal range and were graded osteopenic. Mechanical parameters (maximum load, maximum stress, stiffness, strain at maximum load, and apparent elastic modulus) and AE event count rates in the load-deformation curve were measured during quasi-static compression loading (deformation rate 0.1 mm/min). For all mechanical parameters, the normal vertebrae had higher values than the osteopenic vertebrae. Cumulative AE event counts until maximum load of the osteopenic vertebrae were much greater than that of normal vertebrae. The vertebrae which were well compressed to the plastic range in the load-deformation curve displayed dome-shaped fracture lines just above the end plates. These results are consistent with the hypotheses that microcracks of osteopenic vertebral bodies are generated and accumulate at lower strains than those of normal vertebrae at a specific site.

Absorptiometry, Photon↗