In order to demonstrate the localization of an anti-allergic agent, Tranilast, in the mast cells, light microscopic radioautography was performed. The mast cells collected from rat peritoneal cavity were incubated for 0 to 60 min in a medium containing 3H-Tranilast. After the incubation, they were fixed, embedded and processed for light microscopic radioautography. The radioautographic silver grains were frequently localized around and over the cytoplasmic granules and their number increased according to the prolongation of incubation time. From the results obtained at present it was demonstrated that Tranilast was rapidly taken into the cytoplasm of mast cells. This phenomenon may suggest an important role of this agent in the inhibition of allergic reactions of mast cells.

Animals↗

PubMedDate not supplied

Design and anti-HIV-1 activity of hammerhead and hairpin ribozymes containing a stable loop.

Three ribozymes, a hairpin ribozyme (HR112) and two hammerhead ribozymes (RZ115 and RZ119) containing a 5'C(UUCG)G3' loop were designed to cleave the U5 region in the long terminal repeat (LTR) of HIV-1 RNA. The t1/2 values of chemically synthesized substrates mediated by three ribozymes were measured. The transformed CEM cells possessing these three ribozyme-encoding genes were challenged with a HIV-1IIIB strain, and two of these three ribozymes, HR112 and RZ119, were shown to possess strong anti-HIV-1 activity.

Anti-HIV Agents↗

PubMedDate not supplied

Biologically active oligodeoxyribonucleotides. 10: anti-HIV-1 activity and stability of modified hexanucleotides containing glycerol-skeleton.

Deoxyribose-moieties of modified hexadeoxyribonucleotide 1, which exhibits anti-HIV-1 activity, were partially replaced with glycerol-moieties. Compound 7 with two glycerylguanines at its 3'-end showed more potent anti-HIV-1 activity and more stability against digestion by nucleases than the parent compound 1.

Animals↗

PubMedDate not supplied

A new fluoroquinolone derivative exhibits inhibitory activity against human immunodeficiency virus type 1 replication.

The inhibitory activity of several fluoroquinolone antibiotics against human immunodeficiency virus type 1 (HIV-1) replication was investigated. R-71762, (+/-) 9-fluoro-3-fluoromethyl-2, 3-dihydro-10-[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2, 3-de][1,4]benzoxazine-6-carboxylic acid, protected MT-4 cells from HIV-1-induced cytopathic effects. Furthermore, the compound inhibited virus replication both in acutely and in chronically HIV-1-infected cells. On the other hand, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin and enoxacin, that were previously reported to be protective against HIV-1-induced cytopathic effects, did not show any protective activity in our assay system. These results indicate that R-71762 is a novel inhibitor of HIV-1 replication and is effective even in HIV-1 chronically infected cells.

Anti-HIV Agents↗

PubMedDate not supplied

Distribution, excretion, and metabolism of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea (ACNU) in rats and mice after iv administration.

Distribution, excretion, and metabolism of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea (ACNU) in healthy rats and mice or tumor-bearing mice were studied with the 14C label in each of two positions of the molecule, the ethylene and pyrimidine moieties. After iv injection of 4 mg/kg of ACNU-14C, radioactivity was distributed widely and disappeared rapidly from the body. The half-life of intact ACNU in rat plasma was about 12 minutes. In both animal species, 72%-95% of the radioactivity was excreted into urine within 24 hours. Early dissociation of renal clearance rate was observed between pyrimidine-14C and ethylene-14C, the former being more rapidly excreted than the latter. Ethylene-14C of ACNU was distributed into tumor tissues of X-5563 plasmacytoma-bearing mice, and a tumor level of radioactivity was observed to be twofold higher than the blood level at 3 hours after injection. The concentrations of several metabolites in plasma and urine were determined. Among these compounds, we found an intramolecular carbamoylating product of ACNU. These results suggest that the isocyanate derived from ACNU does not react with any biologic macromolecules, and that the chloroethyl moiety of ACNU has a very important role in the manifestation of the antitumor activity.

Animals↗