Anti-AIDS agents. 46. Anti-HIV activity of harman, an anti-HIV principle from Symplocos setchuensis, and its derivatives.

Matairesinol (1) and harman (5), identified from Symplocos setchuensis, were found to inhibit HIV replication in H9 lymphocyte cells. Anti-HIV evaluation of 28 derivatives of 5 revealed that compound 19 showed potent activity with EC(50) and therapeutic index values of 0.037 microM and 210, respectively.

Determination of norepinephrine in microdialysis samples by microbore column liquid chromatography with fluorescence detection following derivatization with benzylamine.

A microbore column liquid chromatographic method is described for the determination of norepinephrine (NE) in microdialysis samples from rat brain. The method is based on precolumn derivatization of NE with benzylamine in the presence of potassium hexacyanoferrate(III) resulting in a highly fluorescent and stable benzoxazole derivative. Typically, a 10-microl sample was mixed with 10 microl derivatization reagent containing 0.45 M Caps buffer (pH 12.0), 0.2 M benzylamine, 10 mM potassium hexacyanoferrate(III), and N,N-dimethylformamide (1:1:1:15, v/v). The derivatization was carried out at 50 degrees C for 20 min. Under these conditions only NE and epinephrine produced high fluorescence yields at excitation and emission wavelengths of 345 and 480 nm, respectively, while fluorescence of other catechols and 5-hydroxyindoles was quenched by 10-100 times. The NE derivative was separated on a reversed-phase column (100 x 1.0 mm i.d., packed with C18 silica, 5 microm) within 10 min with no late eluting peaks. The mobile phase consisted of 40 mM Britton-Robinson buffer (pH 7.5) containing 1 mM didodecyldimethylammonium bromide and acetonitrile (34%, v/v), the flow rate was 40 microl/min. The limit of detection (signal-to-noise ratio of 3) for NE was 90 amol in 10 microl sample injected. Microdialysis samples were collected in 5-min intervals from the probes implanted in the hippocampus, frontal cortex, or hypothalamus of awake rats. The basal extracellular NE levels in the respective areas were 4.7 +/- 0.9, 1.8 +/- 0.3, and 0.8 +/- 0.2 fmol/10 microl (mean +/- SE, n = 7). Perfusion with a Ringer solution containing 100 mM K+ increased hippocampal NE levels by 700%, while NE uptake inhibitors maprotiline and amitriptyline administered orally or subcutaneously increased extracellular NE in the frontal cortex by about 300%. On the other hand, reserpine (5 mg/kg) reduced cortical NE levels by 40% 3 h after the administration. This new fluorescence derivatization method provides better selectivity, sensitivity, and speed for NE determination than the electrochemical detection since no late-eluting compounds such as dopamine, serotonin, and their metabolites are detectable in the chromatograms of the microdialysis samples.

Histidinomycin, a new antifungal antibiotic.

A new antifungal antibiotic named histidinomycin was isolated from the broth filtrate of a streptomycete, tentatively designated as isolate H 878-MY 1. Histidinomycin was purified as the monohydrochloride and the molecular formula was proposed to be C22H30N8O11.HCl. The antibiotic gave histidine by acid hydrolysis. Histidinomycin showed rather narrow antimicrobial spectrum for only few genera of phytophathogenic fungi.

[A case of primary reticulum cell sarcoma of the brain with uveitis (author's transl)].

In 1972, Neault and his co-workers reported seven cases of uveitis associated with intracranial reticulum cell sarcoma. Recently we have experienced a similar case for the first time in Japan. A 32-year-old woman registered on March 10, 1971, complaining of blurred vision in the left eye for about two weeks. By ophthalmic examination, left posterior uveitis was diagnosed but the etiology was unknown. Treatment with corticosteroids was begun, but her left eye continued to fail in spite of the treatment. In August, 1971, she complained of weakness of left arm and leg, and in October, she suffered from severe headache and vomiting. At that time, uveitis appeared in the right eye too. Neurological findings and carotid angiogram indicated a right cerebral lesion. On November 5, 1971, a right frontoparietal craniotomy was performed but no tumor was found. Since then her neurological and eye symptoms had been progressively worse. The patient died on July 12, 1972. Postmortem examination revealed the tumor infiltrating in the bilateral diencephalon, left internal capsule, left lenticular nucleus, left temporal lobe, midbrain, pons, left dentate nucleus, optic chiasma and intracranial portion of the optic nerves. But no tumor was found at any other parts of the body. Histologically the tumor was a reticulum cell sarcoma. The eyeballs were not examined histologically, but the uveitis in this case was thought to be closely related to the intracranial reticulum cell sarcoma. If the uveitis is resistant to the treatment, we must consider a possibility of reticulum cell sarcoma of the brain.