Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes

We have examined the effects of ginseng on the induction and repair of gamma-ray-induced DNA double strand breaks (dsb) using neutral filter elution technique at pH 9.6 in cultured murine spleen lymphocytes. Ginseng water extract 500 micrograms/ml was added to the culture medium either for 48 hours prior to irradiation. Ginseng extract showed protective effect against the formation of dsb when it was treated for 48 hours before 100 Gy gamma-ray-irradiation. While repair was almost completed until 220.2 minutes after irradiation, DNA repair of irradiated cells in the presence of ginseng extract was did not return to the corresponding control levels even after 621.8 minutes. From these data, it could be calculated that ginseng reduced the relative strand scission factor (RSSF) by about 2. Therefore, it could be concluded that ginseng has radioprotective effect against gamma-ray induced DNA dsb and repair in cultured mouse lymphocytes.     

Studies on constituents of Korean basidiomycetes (L)

To find antitumor metabolites in Korean basidiomycetes, the shake-cultured mycelia of eight of the higher fungi were extracted with hot water and the extracts, after being partially purified, were subjected toin vivo antitumor test. When administeredi.p. at the dose of 30mg/kg/day for ten consecutive days into the female ICR mice, which had been implanted with 1×10⁵ cells of sarcoma 180 twenty-four hours before the first injection, the extracts ofAgaricus campestris, Lyophyllum decastes, Lyophyllum ulmarium, Armillaria tabescence andCalvatia exipulitormis respectively showed inhibition ratios of 64.1%, 65.4%, 60.0%, 53.0% and 49.3%. These five species were selected for further study, whereas the extracts ofPhallus impudicus, Coprinus comatus andPholiota squarrosa which showed the inhibition ratios of 31.2%, 33.5% and 19.0% were discontinued.     

Synthesis of hexaprofen [2-(4-cyclohexylphenyl) propionic acid]

A novel preparative method for hexaprofen, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of cyclohexylbenzene with ethyl α-chloro-α-(methylthio) acetate1 and α-chloro-α-(methylthio) acetonitrile2 afforded ethyl 2-(methylthio)-2-(4-cyclohexylphenyl) acetate7 and 2-methylthio-2-(4-cyclohexylphenyl) acetonitrile8, respectively. Compounds7 and8 were converted into the corresponding ethyl 2-methylthio-2-(4-cyclohexylphenyl) propionate9 and 2-methylthio-2-(4-cyclohexylphenyl) propionitrile10 by methylation with sodium hydride and methyl iodide. Hexaprofen13 was prepared by hydrolysis of ethyl 2-(4-cyclohexylphenyl) propionate11 and of 2-(4-cyclohexylphenyl) propionitrile12 followed by desulfurization of compounds9 and10.     

Determination of N,N-dimethylaniline in penicillins by GC-MS

A quantitative GC-MS spectrometric assay was used for the determination of residual N,N-dimethylaniline as a contaminant in commercial penicillin derivatives from various sources. The assay utilizes selective ion focusing to monitor in a GC effluent the molecular ions of DMA generated by electron impact ionization. This method includes dissolution of the sample in alkaline solution, extraction of organic base with cyclohexane and injection into GC-MS with a 3% OV-17 column. Levels of 50 ppb of DMA were easily measured with a coeffecient of varation less than 5% and recoveries from spiked samples exceeded 97%. The results of the determinations of DMA in various commercial penicillins were relatively free of this contaminant.     

Association between blood lead concentrations and body iron status in children.

Blood lead concentrations and body iron status were investigated in 279 children. Blood lead concentrations showed no increase during iron depletion phase (stage I) but markedly increased from the phase of iron deficient erythropoiesis (stage II). Increased blood lead concentrations in anaemic subjects significantly decreased after iron supplementation.     

Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on immobilization stress-induced antinociception in the mouse.

The effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) 3-isobutyl-1-methylxanthine (IBMX), cholera toxin (CTX) and pertussis toxin (PTX) administration on immobilization-induced antinociception were studied in ICR mice. Antinociception was assessed by the tail-flick assay. Immobilization of the mouse increased inhibition of the tail-flick response for at least 1 h. The pretreatment with i.t. IBMX (0.01-1 ng), but not i.c.v. IBMX, significantly attenuated immobilization-induced inhibition of the tail-flick response. The pretreatments with i.c.v. PTX (0.05-0.5 microg) as well as i.t. CTX, but neither i.c.v. CTX (0.05-0.5 microg) nor i.t. PTX, potentiated the inhibition of the tail-flick response induced by immobilization stress. Our results suggest that spinally located phosphodiesterase appears to be involved in the production of immobilization stress-induced antinociception. In addition, inactivation of supraspinally located PTX-sensitive G-proteins and spinally located CTX-sensitive G-proteins may modulate immobilization stress-induced antinociception.     

Association of hyperglycemia and markers of hepatic dysfunction with dextrose infusion rates in Korean patients receiving total parenteral nutrition.

The association of hyperglycemia and markers of hepatic dysfunction with dextrose infusion rates in Korean patients receiving total parenteral nutrition (TPN) was studied. A retrospective study of 122 patients with normal glucose levels and liver function tests (LFTs) was conducted. Pharmacy and medical records of all patients who received TPN from three university-affiliated teaching hospitals in Korea between January 1998 and December 1999 were reviewed. Each patient was categorized as receiving dextrose at (1) < or = 5 or > 5 mg/kg/min and (2) < or = 4, 4.1-5, 5.1-6, or > 6 mg/kg/min. Fifty-five patients received dextrose at a rate of > 5 mg/kg/min for 15.1 +/- 12.8 days and 67 patients at a rate of < or = 5 mg/kg/min for 10.1 +/- 6.8 days. Two patients in each group did not have follow-up glucose levels. Of the 53 patients in the > 5 mg/kg/min group, 16 exhibited hyperglycemia, compared with 21 of the 65 receiving lower rates of dextrose infusion. Elevated aspartate transaminase was the most common abnormal LFT value in both groups (25% and 29% in the < or = 5- and > 5-mg/kg/min groups, respectively). In the group receiving dextrose at > 5 mg/kg/min, 22.2% had two hepatic enzyme levels elevated concurrently, while 18.5% had two hepatic enzyme levels elevated in the group receiving dextrose at < or = 5 mg/kg/min. Regression analysis revealed that duration of TPN and dextrose infusion rate were positively correlated with blood glucose levels and that duration of TPN was positively correlated with abnormal LFT values. A retrospective study of Korean patients revealed no significant difference in the risk of hyperglycemia or hepatic dysfunction between those receiving < or = 5 and > 5 mg/kg/min dextrose infusion in their TPN.     

Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system.

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content.