Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer

To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirus-mediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone.     

Fatal peritonitis due to Trichoderma sp. in a patient undergoing continuous ambulatory peritoneal dialysis

We describe a rare case of peritonitis caused by an unusual fungus, Trichoderma sp., in a patient on continuous ambulatory peritoneal dialysis. Management of the patient consisted of Tenckhoff catheter removal and antifungal chemotherapy, but the patient died.     

New prenylflavonoids from Artocarpus communis

Five new prenylflavonoids, artocommunols CA (1), CB (2), CC (3), CD (4), and CE (5), were isolated from the cortex of the roots of Artocarpus communis, along with the known compound cyclomorusin. The structures of 1-5 were determined by spectral methods.     

Secoiridoid glucosides with free radical scavenging activity from the leaves of Syringa dilatata

Activity-guided fractionation of the EtOAc and MeOH extract of the leaves of Syringa dilatata NAKAI furnished one free radical scavenger, the secoiridoid glucoside oleuropein together with ligstroside and an iridoid glucoside, syringopicroside. Oleuropein interacted with the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and showed an IC(50) value of 40.4 microM. L-Ascorbic acid as a positive control showed an IC(50) value of 50.3 microM.     

Protective effect of Rhodiola sachalinensis extract on carbon tetrachloride-induced liver injury in rats

This study was carried out to investigate the protective effect of an aqueous extract from the root of Rhodiola sachalinensis (RSE) on liver injury induced by repetitive administration of carbon tetrachloride in rats. RSE was given orally to rats at doses of 50, 100 or 200 mg/kg throughout the carbon tetrachloride treatment for 28 days. In rats treated with carbon tetrachloride, the levels of hydroxyproline and malondialdehyde (MDA) in the liver, and serum enzyme activities were significantly increased. RSE treatment significantly reduced the levels of liver hydroxyproline and MDA, and serum enzyme activities, in accordance with improved histological findings. Immunohistological findings indicated RSE treatment inhibited hepatic stellate cell activation, which is a major step for collagen accumulation during liver injury. These data suggest that RSE protects the liver from repetitive injury induced by carbon tetrachloride in rats.     

Emergence of ceftriaxone-resistant Salmonella isolates and rapid spread of plasmid-encoded CMY-2-like cephalosporinase,Taiwan

Of 384 Salmonella isolates collected from 1997 to 2000 in a university hospital in Taiwan, six ceftriaxone-resistant isolates of Salmonella enterica serovar Typhimurium were found in two patients in 2000. The resistance determinants were on conjugative plasmids that encoded a CMY-2-like cephalosporinase. During the study period, the proportion of CMY-2-like enzyme producers among Escherichia coli increased rapidly from 0.2% in early 1999 to >4.0% in late 2000. Klebsiella pneumoniae isolates producing a CMY-2-like beta-lactamase did not emerge until 2000. The presence of bla(CMY)-containing plasmids with an identical restriction pattern from Salmonella, E. coli, and K. pneumoniae isolates was found, which suggests interspecies spread and horizontal transfer of the resistance determinant. Various nosocomial and community-acquired infections were associated with the CMY-2-like enzyme producers. Our study suggests that the spread of plasmid-mediated CMY-2-like beta-lactamases is an emerging threat to hospitalized patients and the public in Taiwan.     

Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives

A series of MDP (muramyldipeptide) or nor-MDP (normuramyldipeptide) analogues modified at the C-terminus post of the molecule by a formation of an ester bond between the carboxylic group of isoglutamine and the hydroxyl function of the respective derivatives of 4-carboxamide-acridine/9-acridone or 1-nitro-9-hydroxyalkylaminoacridines were synthesized as potential anticancer agents. The compounds O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-(ethylamino)-1-nitroacridine ester 3j and O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-propylamino-1-nitroacridine ester 3k exhibited high in vitro cytotoxic activity against a panel of human cell lines, prostate cancer and AIDS-related lymphoma (ARL). Analogue 3j was also active in vivo in the hollow fiber assay. Antitumor activity of both compounds were tested in vivo against difference human tumor xenograft, but only analogue 3k showed in vivo activity against sc UACC-62 melanoma in mice.     

Inhibition of smooth muscle contraction by magnolol and honokiol in porcine trachea

Magnolol and honokiol are the two major phenolic constituents of the plant medicine "Houpo" ( Magnolia obovata), which is used in the treatment of chest tightness and asthma. The aim of this study was to investigate the influence of magnolol and honokiol on smooth muscle tone in porcine trachea. Magnolol and honokiol (0.1 - 100 microM) inhibited carbachol- and high K +-induced muscle contractions in a concentration-dependent fashion, but did not affect basal muscle tension. After washout of these pretreatments, carbachol- and high K +-evoked muscle contractions were still abolished, suggesting that the inhibition was irreversible. Magnolol and honokiol also concentration-dependently decreased the Ca 2+-dependent muscle contraction induced by high K + depolarization. Ca 2+ channel antagonists attenuated carbachol-induced muscular response by approximately 30 %, but did not further potentiate the inhibitory actions of magnolol and honokiol on muscle contraction. However, the inhibitory effects of magnolol and honokiol on carbachol-evoked muscular contractile response were partially reversed after removal of Ca 2+ channel antagonist pretreatment. Alternatively, caffeine-elicited muscle contractions were not altered by magnolol, honokiol, and verapamil. In conclusion, the relaxant effects of magnolol and honokiol on porcine tracheal smooth muscle suggest an association with the blockade of Ca 2+ influx through voltage-operated Ca 2+ channels instead of Ca 2+ release from intracellular Ca 2+ stores. The magnolol- and honokiol-induced inhibitions on tracheal smooth muscle contraction may be relevant to the claimed therapeutic effects of the extract from magnolia bark and contribute to their pharmacological effects by acting as anti-asthmatic agents.     

Enzymatic preparation of ginsenosides Rg2, Rh1, and F1 from protopanaxatriol-type ginseng saponin mixture

During investigations on the hydrolysis of a protopanaxatriol-type saponin mixture by various glycoside hydrolases, it was found that two minor saponins, ginsenosides Rg 2 and Rh 1, were formed in high yields by crude beta-galactosidase from Aspergillus oryzae and crude lactase from Penicillium sp., respectively. Moreover, a crude preparation of naringinase from Penicillium decumbens readily hydrolyzed a protopanaxatriol-type saponin mixture to give an intestinal bacterial metabolite, ginsenoside F 1 as the main product. A crude preparation of hesperidinase from Penicillium sp. selectively hydrolyzed ginsenoside Re into ginsenoside Rg 1. This is the first report on the enzymatic preparation of minor saponins, ginsenosides Rg 2 and Rh 1, and of an intestinal bacterial metabolite, ginsenoside F 1, with a high efficiency from a protopanaxatriol-type saponin mixture.