Horizontal deflection of single particle in a paramagnetic fluid.

This paper describes the horizontal deflection behaviour of a single particle in paramagnetic fluids under a high-gradient superconducting magnetic field. A glass box was designed to carry out experiments and test assumptions. It was found that the particles were deflected away from the magnet bore centre and particles with different density and/or susceptibility settled at a certain position on the container floor due to the combined forces of gravity and magneto-Archimedes as well as lateral buoyant (displacement) force. Matlab was chosen to simulate the movement of the particle in the magnetic fluid, the simulation results were in good accordance with experimental data. The results presented here, though, are still very much in their infancy, which could potentially form the basis of a new approach to separating materials based on a combination of density and susceptibility.

Phase II and pharmacokinetic study of high-dose methotrexate in the treatment of advanced gynecologic malignancy. A Southwest Oncology Group Trial.

Fifteen patients with advanced or recurrent gynecologic malignancy were treated with high-dose methotrexate (HDMTX) (1-8 g/M2) and citrovorum factor rescue (10-100 mg/M2). One complete response (13%) and two improved responses occurred in eight patients (25%) with squamous cell carcinoma and one of seven patients (14%) with nonsquamous nontrophoblastic carcinoma had stable disease for 7 months. The median duration of survival in the squamous group was 9 months and in the nonsquamous groups 6.5 months. Mean serum MTX concentrations were proportional to the doses administered and typical two compartment plasma disappearance curves were seen. Adverse toxic reactions were not observed at serum MTX levels less than 7.8 X 10(-7) M at 24 hr and 1 X 10(-7) M at 48 hr post-MTX. Hematopoietic toxicity occurred most frequently with leukopenia observed in 19.5% of courses. Hepatic, renal, gastrointestinal, and dermatologic toxicities were observed infrequently. Drug-induced nephrotoxicity occurred in one patient and possibly related leukoencephalopathy occurred in another patient. On the basis of the relatively low response rate observed in this trial and the high expense of HDMTX therapy, the value of such therapy may be limited in advanced nontrophoblastic gynecologic cancer.

1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones: a series with stimulant and depressant activities.

A series of 1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones was synthesized primarily by catalytic hydrogenation of the corresponding 1-(substituted benzyl)-2(1H)-pyrimidone. The pharmacological evaluation of these compounds in mice revealed a unique profile that included evidence of CNS stimulation and depression within the series and in the same compounds. Some members of this series induced signs of only CNS stimulation, some compounds caused signs of only CNS depression and skeletal muscle relaxation, and some caused signs of both stimulation and depression in the same animal. This apparent dual activity was assessed further in mice with antidepressant tests based on tetrabenazine antagonism and with antianxiety/anticonvulsant tests on the antagonism of a number of convulsants. The 4-chloro-, 4-fluoro-, 4-bromo-, and 3,4-dichlorobenzyl compounds exhibited antidepressant and antianxiety activities in the same dose range. Among these four compounds, the 3,4-dichlorobenzyl compound possessed the lowest antitetrabenazine (17 mg/kg po) and antipentylenetetrazol (23 mg/kg po) ED50 values. The 4-fluoro compound antagonized tetrabenazine-, pentylenetetrazol-, and isoniazid-induced tonic convulsions in the same dose range (congruent to 50 mg/kg po).

4-Acetoxy-1,2,3,4-tetrahydro-2,2-dimethyl-6,7-methylenedioxyisoquinolinium iodide, an acetylcholine analog.

4-Acetoxy-1,2,3,4-tetrahydro-2,2-dimethyl-6,7-methylenedioxyisoquinolinium iodide, an analog of acetylcholine, was synthesized and a pharmacological profile of its GI effects was compiled. The agent inhibited dog colonic contraction in response to pelvic nerve stimulation and to acetylcholine. In rats, the compound markedly reduced gastric acid output and the volume of gastric secretions. The lack of inhibition of chromodacryorrhea production in response to carbachol indicates a lack of anticholinergic action. The agent failed to affect the acute inflammatory response of the rat hindpaw in response to carrageenan. The precursor of the compound was ineffective in the pharmacological tests.

Anti-inflammatory 1-substituted 2-imidazolidinones.

The synthesis and anti-inflammatory activity of a series of 1-substituted 2-imidazolidinones are reported. These compounds exerted marked anti-inflammatory activity in the carrageenan-induced hindpaw edema assay in the rat in doses that failed to elicit side effects. Their ED50 values were near the value of aspirin but markedly higher than the value of indomethacin.