The use of collagen content as determined by spectral domain polarization-sensitive optical coherence tomography to assess colon anastomosis healing in a rat model.

BACKGROUND/PURPOSE: Many studies have been undertaken to prevent anastomosis leakage of the colon, and several methods have been used to assess anastomosis healing, such as measurement of bursting pressure or hydroxyproline (a marker of collagen) content at the anastomosis site. However, these methods are inappropriate for comparing anastomosis healing at two time points in the same animals. In the present study, we measured the collagen level by spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) to assess anastomosis healing. METHODS: Sprague-Dawley rats were divided into groups C (saline-administered controls; study group) and M [a 5-fluorouracil (5-FU)-administered experimental group]. Immediately after end-to-end anastomosis of the colon, SD-PS-OCT images of anastomoses were taken (baseline). Animals were administered saline or 5-FU for 7 days. On the 7th postoperative day, SD-PS-OCT images were acquired, a histopathologic exam was performed, and hydroxyproline levels as well as mRNA expressions of collagen-1 and collagen-3 were measured at the anastomosis site. RESULTS: Fibroblast proliferation and inflammatory cell infiltration were greater in group C than in group M. The mRNA expressions of collagen-1 and collagen-3 were substantially higher in group C. Hydroxyproline levels were higher in group M than in group C. Though collagen levels measured by SD-PS-OCT at 7 days were elevated compared with baseline in group C, no such changes were observed for group M. CONCLUSION: Collagen levels at the colon anastomosis site, measured with SD-PS-OCT, were not increased at 7 days postoperatively versus baseline when 5-FU was injected, but were increased in saline-treated controls. The measurement of collagen content by SD-PS-OCT was found to provide a good means of assessing anastomosis healing, because it allows in situ assessment of collagen contents at baseline and during the postoperative period.

Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai.

Antimicrobial activity of the 18 prenylated flavonoids, which were purified from five different medicinal plants, was evaluated by determination of MIC using the broth microdilution methods against four bacterial and two fungal microorganisms (Candida albicans, Saccaromyces cerevisiae, Escherichia coli, Salmonella typhimurium, Staphylococcus epidermis and S. aureus). Papyriflavonol A, kuraridin, sophoraflavanone D and sophoraisoflavanone A exhibited a good antifungal activity with strong antibacterial activity. Kuwanon C, mulberrofuran G, albanol B, kenusanone A and sophoraflavanone G showed strong antibacterial activity with 5-30 microg/ml of MICs. Morusin, sanggenon B and D, kazinol B, kurarinone, kenusanone C and isosophoranone were effective to only gram positive bacteria, and broussochalcone A was effective to C. albicans. IC50 values of papyriflavonol A, kuraridin, sophoraflavanone D, sophoraisoflavanone A and broussochalcone A in HepG2 cells were 20.9, 37.8, 39.1, 22.1, and 22.0 microg/ml, respectively. These results support the use of prenylated flavonoids in Asian traditional medicine to treat microbial infection and indicate a high potential for prenylated flavonoids as antimicrobial agents as well as anti-inflammatory agents.

Two photon absorption properties of 1,3,5-tricyano-2,4,6-tris(styryl)benzene derivatives.

Two-photon absorption (TPA) properties of 1,3,5-tricyano-2,4,6-tris(styryl)benzene derivatives have been investigated. Comparison of the absorption and fluorescence spectra reveals that these compounds show large Stokes shifts, which increase gradually as the conjugation length increases. One-photon absorption and excitation spectra are similar except that the latter exhibit several peaks near lambda(max). It is also found that the one- and two-photon-induced fluorescence excitation spectra are quite similar, which indicates that the one- and two-photon allowed-excited states are the same. The peak TPA cross section values (delta(max)) measured with nanosecond pulses by the two-photon-induced fluorescence method are in the range (50-2620) x 10(-50) cm4 s/photon. The delta(max) value increases as the donor strength and conjugation length increase. A linear relationship is observed between delta(max) and beta, and this delta-beta relationship is found to serve as a useful synthetic strategy for the design of novel TPA dyes with the octupolar structure.

Cyclooxygenase-2 inhibitory cerebrosides from phytolaccae radix.

A mixture of cerebrosides, called poke-weed cerebrosides, was purified from Phytolaccae Radix (Phytolaccaceae) and characterized as 1-O-beta-D-glucopyranosides of phytosphingosine type ceramides comprised of a common long chain base (2S,3S,4R,8Z)-2-amino-8-octadecene-1,3,4-triol and fatty acids. The fatty acyl chain of ceramide moieties was determined as (2R)-2-hydroxypentacosanoic acid, (2R)-2-hydroxylignoceric acid, (2R)-2-hydroxytricosanoic acid, (2R)-2-hydroxybehenic acid, (2R)-2-hydroxypalmitic acid, and palmitic acid. The pokeweed cerebroside inhibited the cyclooxygenase-2 dependent phase of prostaglandin D2 generation in bone marrow-derived mast cells in a concentration dependent manner with an IC50 of 6.2 microg/ml.

Constituents and the antitumor principle of Allium victorialis var. platyphyllum.

To search for cytotoxic components from Allium victorialis, MTT assays on each extract and an isolated component, gitogenin 3-O-lycotetroside, were performed against cancer cell lines. Cytotoxicities of most extract were shown to be comparatively weak, though IC50 values of CHCl3 fraction was found to be <31.3-368.4 microg/ml. From the incubated methanol extract at 36 degrees C, eleven kinds of organosulfuric flavours were predictable by GC-MS performance. The most abundant peak was revealed to be 2-vinyl-4H-1,3-dithiin (1) by its mass spectrum. Further, this extract showed significant cytotoxicities toward cancer cell lies. Silica gel column chromatography of the n-butanol fraction led to the isolation of gitogenin 3-O-lycotetroside (3) along with astragalin (4) and kaempferol 3, 4'-di-O-beta-D-glucoside (5). This steroidal saponin exhibited significant cytotoxic activities (IC50, 6.51-36.5 microg/ml) over several cancer cell lines. When compound 3 was incubated for 24 h with human intestinal bacteria, a major metabolite was produced and then isolated by silica gel column chromatography. By examining parent- and prominent ion peak in FAB-MS spectrum of the metabolite, the structure was speculated not to be any of prosapogenins of 3, suggesting that spiroketal ring were labile to the bacterial reaction. These suggest that disulfides produced secondarily are the antitumor principles.

Cinnamaldehydes inhibit cyclin dependent kinase 4/cyclin D1.

A series of cinnamaldehydes was synthesized for the study of inhibitory activity against cyclin dependent kinases (CDKs). A couple of compounds selectively inhibited cyclin D1-CDK4 with an IC50 value of 7-18 microM.

Natural and synthetic analogues of actinomycin D as Grb2-SH2 domain blockers.

Natural analogues (D, C2, and VII) of actinomycin inhibit Grb2 SH2 domain binding with phosphopeptide-derived from Shc in vitro and in intracellular system. To study structure-activity relationships, 13 actinomycin analogues were synthesized and we found that the inhibition activity depended on the substituents of cyclic peptide groups in actinomycin and two analogues with Tyr residue are the most potent inhibitors with IC50 value of 0.5 and 0.8 microM, respectively.

Vitexicarpin, a flavonoid from the fruits of Vitex rotundifolia, inhibits mouse lymphocyte proliferation and growth of cell lines in vitro.

Certain flavonoids having a C-2,3-double bond were reported to show an inhibitory activity against T-lymphocyte proliferation, but not against B-lymphocyte proliferation in vitro. In the course of these studies, vitexicarpin (3',5-dihydroxy-3,4',6,7-tetramethoxyflavone) isolated from the fruits of Vitex rotundifolia was found to show potent inhibition against lymphocyte proliferation. Vitexicarpin inhibited T-lymphocyte proliferation as well as B-lymphocyte proliferation at > 0.1 microM. IC50's were approximately 0.7 microM both for T- and B-cell proliferation. The inhibitory activity of vitexicarpin was reversible. Vitexicarpin also inhibited the growth of certain cancer cell lines, EL-4 and P815.9 (IC50 = 0.25-0.3 microM). These results suggest that vitexicarpin may be a potential therapeutic agent involved in inflammatory/immunoregulatory disorders such as rheumatoid arthritis and lymphomas.

Inhibition of lysoPAF acetyltransferase activity by flavonoids.

OBJECTIVE AND DESIGN: Several kinds of flavonoids, widely distributed natural products of the vegetable kingdom which possess anti-inflammatory activity, were examined for inhibitory effects on the acetyl-CoA: 1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lysoPAF) acetyltransferase activity. METHODS: Acetyl-CoA:lysoPAF acetyltransferase activity was determined using homogenates of a rat mucosal-type mastocytoma cell line, RBL-2H3 as an enzyme source. The production of platelet-activating factor (PAF) in rat peripheral white blood cells stimulated with the calcium ionophore A23187 was studied. RESULTS: Of the flavonoids tested, luteolin and quercetin exhibited significant inhibitory effects (IC50, 45 microM and 80 microM, respectively), whereas other structurally-related flavonoids failed to affect the lysoPAF acetyltransferase activity. Luteolin did not suppress the activity of choline acetyltransferase, suggesting that the inhibition observed here was specific. Luteolin also inhibited the production of PAF in rat peripheral white blood cells. CONCLUSIONS: These results indicate that luteolin could become a leading compound for developing a novel type of anti-inflammatory, anti-allergic drugs that target lysoPAF acetyltransferase.

GERI-BP002-A, novel inhibitor of acyl-CoA: cholesterol acyltransferase produced by Aspergillus fumigatus F93.

A new inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated GERI-BP002-A, was isolated from the culture broth of Aspergillus fumigatus F93 by acetone extraction, EtOAc extraction, SiO2 column chromatography and reverse phase HPLC. Spectroscopic analyses of the compound identified bis (2-hydroxy-3-tert-butyl-5-methylphenyl) methane as the structure and its molecular weight and formula to be 340 and C23H32O2, respectively. GERI-BP002-A inhibited ACAT activity by 50% at the concentration of 50 microM in an enzyme assay system using rat liver microsomes.