Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional oriental herbal medicine, on the growth of influenza A/Aichi/2/68 virus.

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 approximately 100 microg/ml) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mphi) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-alpha was gradually accumulated in ZOR-CM by the induction of TNF-alpha mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-alpha after the formation of an immune complex with anti-TNF-alpha monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-alpha.

Induction of inducible nitric oxide (NO) synthase mRNA and NO production in macrophages infected with influenza A/PR/8 virus and stimulated with its ether-split product.

We investigated the inductive activity of infective influenza A/PR/8/34 (PR8) virus and its ether-split product (ESP) on the expression of inducible nitric oxide (NO) synthase (iNOS) and NO production in RAW264.7 (RAW) cells, a murine macrophage (M psi) cell line, and thioglycolate-elicited peritoneal M psi (TPM). In both cells, PR8 virus infection induced iNOS mRNA between 4 hr and 24 hr, attaining a peak value at 12 hr. In correlation with induction of iNOS mRNA, NO amounts increased significantly from 12 to 24 hr. Moreover, this study demonstrated that ESP with the same hemagglutination titer as PR8 virus could induce iNOS mRNA and NO production, although the inductive activity of ESP was weaker than that of PR8 virus. Considering the dual role (beneficial and detrimental roles) of NO on certain inflammatory disorders and virus infections, the inductive activity of influenza virus on the iNOS-mediated NO production independent of its infectivity might contribute to a modification of influenza virus infection.

Synthesis of a new class of furan-fused tetracyclic compounds using o-quinodimethane chemistry and investigation of their antiviral Activity.

The synthesis and evaluation of antiviral activity of new furan-fused tetracyclic compounds are described. The syntheses were satisfactorily achieved on the basis of o-quinodimethane chemistry, using furan-containing benzocyclobutene derivatives as a substrate, in high generality and stereoselectivity. The various derivatives thus synthesized were examined on their inhibitory activity on virus growth using a hemagglutinin (HA) method, leading to a discovery of promising candidates for new antiviral drugs having high activity and good therapeutic index.

Inducible activity of ginger rhizome (Zingiber offifinale Rosc.) on the mRNA expression of macrophage-inducible nitric oxide (NO) synthase and NO production in a macrophage cell line, RAW264.7 cells.

We have investigated the effect of Zingiber offifinale Rosc. (ZOR) on macrophage-inducible nitric oxide (NO) synthase (macNOS) mRNA expression and NO production in RAW264.7 cells, a murine macrophage cell line; 100 microg/ml ZOR can induce macNOS mRNA expression, but induction effects at a dose below 10 microg/ml were weak or negligible. Kinetic studies showed that macNOS mRNA can be detected from 4 hours to 24 hours after dosing, with a peak at 8 hours. In accordance with the induction of macNOS mRNA expression, NO concentrations increased from 3.4 microM at 2 hours to almost 150 microM at 24 hours, reflecting a longer period of macNOS mRNA expression. The activity of ZOR can be considered to contribute, at least in part, to the beneficial effects of ZOR through the macNOS-mediated activation of the biodefense mechanism.

A case-control study of purple urine bag syndrome in geriatric wards.

The clinical background of purple urine bag syndrome (PUBS) has not yet been well characterized. In previous reports, clinical, biochemical, or bacteriological analyses were carried out using urine or bacteria from a limited number of patients. Other than one report, we are not aware of any case-control studies that compared the clinical, biochemical, or bacteriological background between patients with and without PUBS. To examine the risk of PUBS, we carried out a case-control study. Twenty-six patients, in three long-term care wards, who had been catheterized for more than 3 months with the same types of balloon catheters and who had the same type of disposable plastic urine bags were enrolled as the PUBS-positive case group (14 patients; 2 men and 12 women), and as the PUBS-negative control group (12 patients; 4 men and 8 women) were enrolled. The data for urine tests (pH, sugar, protein, leukocyte counts, and bacterial yields and species) were compared for the two groups. A relatively higher prevalence of PUBS was observed in female and alkaline-urine-producing patients. Bacteriological studies, using fresh urine collected through the catheter, showed that the bacterial counts were significantly higher, by 1 to 2 logs, in most samples from the case group than those from the control group (P = 0.012). Although a total of 66 bacterial strains, belonging to 12 separate species, were isolated from the urine accumulated in bags, no causative relationship between bacterial species and PUBS was observed. These data suggest that a higher bacterial yield in urine acts as the most important factor in PUBS, in combination with other facilitating factors, such as female-specific ones and the alkaline condition of urine.

Additional inhibitory effect of tea extract on the growth of influenza A and B viruses in MDCK cells.

It has been previously reported that green-tea extract (GTE) inhibits the growth of influenza virus by preventing its adsorption. In this study, we further investigated whether GTE exerts an additional inhibitory effect on the acidification of intracellular compartments such as endosomes and lysosomes (referred to as ELS) and thereby inhibits the growth of influenza A and B viruses in Madin-Darby canine kidney cells. The vital fluorescence microscopic study showed that GTE inhibited acidification of ELS in a concentration-dependent manner. Moreover, the growth of influenza A and B viruses was equally inhibited when the cells were treated with GTE within as early as 5 to 15 min after infection, depending on the virus strains. The fact that (-)epigallocatechin (EGC), one of major catechin molecules in GTE, exerts the inhibitory effects on the acidification of ELS and virus growth in a manner similar to that of GTE strongly suggests that EGC is one of the active components in the extract.