The pharmacokinetics of two 2-substituted phenylmetyrapone analogues, 2-methoxyphenylmetyrapone (2-MPMP) and 2-bromophenylmetyrapone (2-BrPMP), developed as potential adrenal imaging agents, were investigated in conscious male rats following an intravenous dose of 25 mg/kg. Arterial blood samples (0.25 ml) were collected at various intervals for up to 7 h after dose and subjected to reversed-phase HPLC analysis. Blood concentrations versus time profile for each compound was determined and the pharmacokinetic parameters calculated using the model-independent approach. Blood concentrations of 2-MPMP declined biexponentially with mean initial (t1/2alpha) and terminal (t1/2beta) half-lives of 3.6 and 23.1 min, respectively. The corresponding area under the curve (AUC(0-infinity)) was 159.3 microg x min/ml, the total blood clearance (CI) was 158.3 ml/min and the volume of distribution (Vd) was 5.2 l. Two metabolites of 2-MPMP, namely 2-hydroxyphenylmetyrapone (2-OHPMP) and 2-methoxyphenylmetyrapone N-oxide (2-MPMP-NO), were detected in the blood and their elimination from blood was almost parallel to that of the parent compound. The maximum blood concentrations (Cmax) of 2-OHPMP and 2-MPMP-NO were approximately 0.9 and 1.7 microg/ml, respectively. Blood concentrations of 2-BrPMP declined monoexponentially with a mean t1/2beta of 12.0 min. The pharmacokinetic parameters for 2-BrPMP were: AUC(0-infinity), 193.7 microg x min/ml; Cl, 131.7 ml/min and Vd, 2.3 l. 2-Bromophenylmetyrapone N-oxide was the only one metabolite detected in the blood, its Cmax and AUC0-infinity were 10.1 microg/ml and 1690.0 microg x min/ml, respectively.

Animals↗

PubMedDate not supplied

Tradescantia-Micronucleus (Trad-MCN) tests on 140 health-related agents.

The Tradescantia-Micronucleus (Trad-MCN) test is a simple short-term bioassay for various gaseous and liquid forms of chemical agents, and physical agents such as radiation. 140 agents, directly or indirectly related to human health, were screened for their mutagenicity. Plant cuttings of young inflorescences, in which the pollen mother cells undergo various stages of meiosis, were maintained in nutrient solution for experimentation. Treatments were made either by absorption of the soluble agents through the stem, by diffusion of gaseous agents through the leaves and buds, by exposure to internal/external radiation or by in situ exposure to air pollutants. Micronuclei formed from damaged chromosomes served as the indicators of mutagenicity. Results of 140 agents tested are listed in 9 different categories. (1) Carcinogens/mutagens, (2) common beverages, (3) common chemicals, (4) drugs, (5) pesticides, (6) common household chemicals, (7) radiation and radioisotopes, (8) in situ monitoring, (9) complex environmental mixtures. Out of 140 agents tested, 52 showed positive, 20 showed borderline positive responses and 5 showed strong toxicity. Test results of 41 agents in the present study showed 67% congruity with Ames test results found in the literature.

Beverages↗

PubMedDate not supplied

Experimental studies of portal venous embolization with iodized oil in rats with experimentally induced liver cancer.

PURPOSE: To assess the feasibility of portal venous embolization (PVE) with iodized oil in the treatment of human hepatocellular carcinoma (HCC), the distribution of iodized oil after PVE and tumor vascularity after hepatic arterial embolization (HAE) with iodized oil was determined in 25 rats with n-nitrosodiethylamine-induced liver cancer. MATERIALS AND METHODS: Under microscopic guidance, HAE with 1 mL of iodized oil was performed in 10 rats. After HAE, low-kilovoltage radiography in four rats and Microfil perfusion techniques in six were used to investigate the distribution of iodized oil and the portal blood supply, respectively. Low-kilovoltage radiography and histologic examination were performed to observe the distribution of iodized oil in 15 rats after PVE with doses of 0.6 mL/kg in each rat. RESULTS: After HAE with iodized oil, it was common that tumor nodules smaller than 5 mm in diameter were filled with Microfil perfused through the portal vein. After PVE, tumor nodules (< 5 mm) were completely filled with iodized oil, while filling defects were observed in larger tumor nodules (> 5 mm), which could have been filled through hepatic arterial perfusion. CONCLUSION: PVE with iodized oil may have a role in the treatment of hepatic malignant tumors, and it may play an important role in early detection and treatment of small tumor nodules (< 5 mm) supplied mainly by the portal vein.

Animals↗

PubMedDate not supplied

Microvasculature architecture of small liver metastases in man. A correlation between microfil vascular preparations and histologic sections.

The hepatic artery and the portal vein of 12 human cadaver livers with metastases of various sizes and origins were injected with Microfil. The microvascular appearances of the metastases were studied in order to receive an explanation to findings at angiography and contrast enhanced computed tomography. Histologic examinations were also performed of Microfil-injected specimens.

Adult↗

PubMedDate not supplied

Transluminal catheter angioplasty of abdominal aorta in Takayasu's arteritis.

Nine patients with Takayasu's arteritis and a long stenotic segment of the abdominal aorta were treated by percutaneous transluminal angioplasty (PTA). Intermittent claudication disappeared in six of seven cases, the femoral pulse reappeared in all five; ankle/arm indices increased in seven cases; elevated blood pressure normalized in seven of eight cases. Seven patients were followed for 3 to 28 months. They were all free of symptoms from the lower extremities. In three patients with or without renal artery stenosis and with hypertension, the blood pressure decreased after PTA of the abdominal aorta only. PTA may be a valuable treatment in Takayasu's arteritis and stenosis of the abdominal aorta.

Adolescent↗