Flavonoids as potential anti-hepatocellular carcinoma agents: recent approaches using HepG2 cell line.

Numerous studies have documented that in cancer therapy flavonoids extracted from traditional Chinese medicine have anti-tumor activity or can enhance efficiency of chemotherapy in combination with chemotherapeutics. Thus, an awareness of flavonoids is needed by physicians and medical researchers. This review provides evidence about anti-hepatocellular carcinoma activity of flavonoids. First, as a common employed in vitro model, profile of HepG2 is shown. Second, the intracellular signaling pathways induced by flavonoids which inhibit the HepG2 cell line are summarized. Third, study situation of anti-HBV/HCV activity of flavonoids is shown. Our review is aimed at providing an understanding of anti-HBV/HCV activity and anti-HCC mechanisms of flavonoids, and an outlook on flavonoids application on cancer therapy.

Shosaikoto increases calprotectin expression in human oral epithelial cells.

BACKGROUND AND OBJECTIVE: Oral epithelial cells help to prevent against bacterial infection in the oral cavity by producing antimicrobial peptides (AMPs). A broad-spectrum AMP, calprotectin (a complex of S100A8 and S100A9 proteins), is expressed by oral epithelial cells and is up-regulated by interleukin-1alpha (IL-1alpha). Shosaikoto (SST) is a traditional Japanese herbal medicine that has immunomodulatory effects and is reported to enhance the levels of IL-1alpha in epithelial cells. The purpose of this study was to investigate the effect of SST on the expression of calprotectin and other AMPs through the regulation of IL-1alpha in oral epithelial cells. MATERIAL AND METHODS: Human oral epithelial cells (TR146) were cultured with SST (at concentrations ranging from 10 to 250 microg/mL) in the presence or absence of anti-IL-1alpha or IL-1 receptor antagonist. The expression of S100A8- and S100A9-specific mRNAs was examined by northern blotting. Calprotectin expression and IL-1alpha secretion were investigated by immunofluorescent staining or ELISA. The expression of other AMPs and IL-1alpha was analyzed by RT-PCR and by quantitative real-time PCR. RESULTS: Shosaikoto (25 microg/mL) significantly increased the expression of S100A8- and S100A9-specific mRNAs and calprotectin protein. Shosaikoto increased S100A7 expression, but had no effect on the expression of other AMPs. The expression of IL-1alpha-specific mRNA and its protein were slightly increased by SST. A neutralizing antibody against IL-1alpha or IL-1 receptor antagonist inhibited SST up-regulated S100A8/S100A9 mRNA expression. CONCLUSION: These results suggest that SST increases the expression of calprotectin and S100A7 in oral epithelial cells. In response to SST, up-regulation of calprotectin may be partially induced via IL-1alpha.

Inhibitory effects of macrocarpals on the biological activity of Porphyromonas gingivalis and other periodontopathic bacteria.

BACKGROUND/AIMS: Macrocarpals, which are phloroglucinol derivatives contained in eucalyptus leaves, exhibit antimicrobial activity against a variety of bacteria including oral bacteria. This study examined effects of macrocarpals A, B, and C on periodontopathic bacteria, especially Porphyromonas gingivalis. METHODS: Macrocarpals A, B, and C were purified from a 60% ethanol-extract of Eucalyptus globules leaves. To investigate antibacterial activity, representative periodontopathic bacteria were cultured in media with or without various amounts of macrocarpals; subsequently, the optical density at 660 nm was measured. Macrocarpal inhibition of P. gingivalis Arg- and Lys-specific proteinases was assessed by spectrofluorophotometric assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The effect of macrocarpals on P. gingivalis binding to saliva-coated hydroxyapatite beads was examined with (3)H-labeled P. gingivalis. RESULTS: Growth of P. gingivalis was inhibited more strongly than growth of Prevotella intermedia or Prevotella nigrescens and Treponema denticola by macrocarpals, however, Actinobacillus actinomycetemcomitans and Fusobacterium nucleatum were much more resistant. Macrocarpals inhibited P. gingivalis Arg- and Lys-specific proteinases in a dose-dependent manner. The enzyme-inhibitory effect of macrocarpals was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis in which hemoglobin degradation by P. gingivalis proteinase was inhibited by macrocarpals. P. gingivalis binding to saliva-coated hydroxyapatite beads was also strongly attenuated by macrocarpals. CONCLUSIONS: Macrocarpals A, B and C demonstrated antibacterial activity against periodontopathic bacteria. Among tested bacteria, P. gingivalis displayed the greatest sensitivity to macrocarpals; additionally, its trypsin-like proteinase activity and binding to saliva-coated hydroxyapatite beads were inhibited by macrocarpals. These results indicate that eucalyptus leaf extracts may be useful as a potent preventative of periodontal disease.

Angiotensin II stimulates platelet-derived growth factor-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation.

Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for microvascular endothelial cells and glial cells in the retina and is thus involved in the development of proliferative diabetic retinopathy. However, relatively little is known about the regulation of PDGF-B gene expression in retinal cells. In this study, we cloned partial complementary DNAs (cDNAs) encoding bovine PDGF-B and examined the effects of angiotensin II (Ang II), which is also implicated in the pathogenesis of diabetic retinopathy, on PDGF-B gene expression in bovine cultured retinal pericytes. Ang II was found to up-regulate PDGF-B messenger RNA (mRNA) levels in bovine retinal pericytes. Telmisartan, a newly developed Ang II type 1 receptor antagonist, or an antioxidant N-acetylcysteine significantly inhibited PDGF-B gene induction in Ang II-exposed pericytes. The present results suggest that Ang II-type 1 receptor interaction could stimulate PDGF-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation and could thus be involved in the progression of diabetic retinopathy.

Hypoglycemic effect of a hot-water extract from defatted sesame (Sesamum indicum L.) seed on the blood glucose level in genetically diabetic KK-Ay mice.

Genetically diabetic (type II) KK-Ay mice, male and 5 weeks of age, were divided into one group of 12 mice that were fed on a basal (BAS) diet and three groups of 6 mice each that were fed on the test diets for 4 weeks. Each test diet contained 4.0% of the hot-water extract (HES) from defatted sesame (Sesamum indicum L.) seed, 1.4% of the water eluent fraction (WFH) of HES or 0.7% of the methanol eluent fraction (MFH) of HES from a glass column packed with HP-20 resin. At the end of the feeding period, the BAS group was divided into the MAL and MALH groups which were respectively force-fed with 1 ml per mouse of a 20% maltose solution in water with or without 4.0% HES. The plasma glucose concentration and amount of urinary excreted glucose were lower from the HES and MFH diets than from the BAS and WFH diets. The levels of plasma glucose and serum insulin were lower in the MALH group than in the MAL group. These results indicate that HES and MFH had a reductive effect on the plasma glucose concentration of KK-Ay mice, and this effect is suggested to have been caused by the delayed glucose absorption.

The cost-effectiveness of methohexital versus propofol for sedation during monitored anesthesia care.

UNLABELLED: We designed this study to test the hypothesis that methohexital is a cost-effective alternative to propofol for sedation during local anesthesia. Sixty consenting women undergoing breast biopsy procedures under local anesthesia were randomly assigned to receive an infusion of either propofol (50 microg x kg(-1) x min(-1)) or methohexital (40 microg x kg(-1) x min(-1)). The sedative infusion rate was titrated to maintain an observer's assessment of alertness/sedation (OAA/S) score of 3 (with 1 = awake/alert to 5 = asleep). Fentanyl 25 microg i.v. was administered as a "rescue" analgesic during the operation. We assessed the level of sedation (OAA/S score), vital signs, time to achieve an OAA/S score of 3 at the onset and a score of 1 after discontinuing the infusion, discharge times, perioperative side effects, and patient satisfaction. The direct cost of methohexital was lower than that of propofol, based on the milligram dosage infused during the operation. The sedative onset (to achieve an OAA/S score of 3) and the recovery (to return to an OAA/S score of 1) times, as well as discharge times, did not differ between the two groups. Patients receiving methohexital had a significantly lower incidence of pain on initial injection compared with those receiving propofol (10% vs 23%). Because the use of methohexital (29.4 +/- 2.7 microg x kg(-1) x min(-1)) for sedation during breast biopsy procedures has a similar efficacy and recovery profile to that of propofol (36.8 +/- 15.9 microg x kg(-1) x min(-1)) and is less costly based on the amount infused, it seems to be a cost-effective alternative to propofol for sedation during local anesthesia. However, when the cost of the drug infused and drug wasted was calculated, there was no difference in the overall drug cost. IMPLICATIONS: When administered to maintain a stable level of sedation during local anesthesia, methohexital is an acceptable alternative to propofol. However, the overall drug costs were similar with the two drugs.

Amino acid sequences of porcine Sp38 and proacrosin required for binding to the zona pellucida.

We previously purified a boar sperm protein, sp38, and demonstrated that this protein bound to the 90-kDa family of zona pellucida (ZP) glycoprotein in a calcium-dependent manner. Sp38 competed with proacrosin for the binding to the zona pellucida. Herein we have isolated cDNA clones encoding sp38 from a boar testis cDNA library in lambda gt11. The amino acid sequence deduced from the cDNA sequence indicated that sp38 is initially synthesized as a 350-residue precursor protein. The N-terminal 51-residue sequence preceded the N-terminus of the mature sp38. Thus, the sp38 precursor is post-translationally modified to produce the mature protein of 299 residues. Immunostaining of sperm cells using an antibody prepared against a fusion protein of sp38 with T7 gene 10 protein suggested that sp38 is localized at the intraacrosomal region and is released after the acrosome reaction. The 11-residue sequence, KRLSKAKNLIE, in sp38 shared a significant degree of similarity with the 8-residue sequence, KRLQQLIE, in the C-terminal region of porcine proacrosin. Both synthetic oligopeptides corresponding to these two sequences inhibited the binding of 125I-labeled sp38 to zona pellucida glycoprotein.

High-energy phosphate metabolism of the myocardium in normal subjects and patients with various cardiomyopathies--the study using ECG gated MR spectroscopy with a localization technique.

Nuclear magnetic resonance spectroscopy (MRS) is a new technique for the evaluation of myocardial metabolism. Recently, localized MRS has been clinically available to measure by a non-invasive method the relative concentrations of the high-energy phosphate metabolites in the myocardium. We performed ECG gated P-31 MRS using ISIS (image-selected in vivo spectroscopy) in 15 normal volunteers, 12 patients with hypertrophic cardiomyopathy, 12 with left ventricular hypertrophy, 6 with dilated cardiomyopathy and 11 with specific heart muscle disease. Myocardial peak height ratios of PCr/gamma-ATP, Pi/gamma-ATP and PCr/Pi were measured. Myocardial P-31 MRS demonstrated a significant decrease in the ratio PCr/ATP in patients with hypertrophic cardiomyopathy and specific heart muscle disease as compared with normal subjects, indicating myocardial metabolic disturbance in these patients. The ratio of PCr/ATP in patients with dilated cardiomyopathy did not differ significantly from that of normal subjects. However, exercise MRS revealed a marked decrease of PCr peak in an asymptomatic patient with dilated cardiomyopathy, which may indicate a latent metabolic disturbance in the myocardium of dilated cardiomyopathy.

Clinical experience with alumina ceramic transcutaneous connector to prevent skin-exit infection around CAPD catheter.

To prevent skin-exit infection, an important CAPD complication, we developed a transcutaneous connector made of Alumina ceramic. The new connector could be downsized, because an Alumina ceramic is characteristically bio-inert, rigid and non-porous. Our animal experiments with Alumina ceramic in soft tissue demonstrated the outstanding bio-compatibility of this material. The shape of the new transcutaneous connector was of simple cylindrical configuration so as to inhibit macrostress beneath the skin. To make contact with this connector in the body, a silicon tube was made into a Swan-necked catheter with a disk-shaped polyester cuff, which was positioned subcutaneously beneath the transcutaneous connector in order to reinforce adhesion to soft tissue. The silicon tube itself was L-shaped in its outside portion just before reaching the connector. We are now using this new transcutaneous connector made of Alumina ceramic on a CAPD catheter in 8 patients. In the longest case of a patient using it, there has been no skin-exit infection for 12 months. Also, there has been virtually no downgrowth phenomenon in the skin around the connector, and the connector and tissue have remained in very close contact, although fibrous connective tissue has been seen to form in the area.

[Successful therapy with tegafur and lentinan after TAE for hepatocellular carcinoma--a case report].

A 46-year-old male (performance status 1) with hepatocellular carcinoma (HCC), which diffusely involved the anterior segment of the right lobe, occluded the second portal branch and metastased to the left lobe (stage IV-A), was on combined therapy with TAE of lipiodol (LPD), mitomycin C (MMC) 10 mg and gelatin sponge at the time of angiography on March 16, 1987. Immunochemotherapy with tegafur suppository (Teg sp) 1,000 mg/day and OK432 i.m. was performed for one month after TAE. Instead of OK432, lentinan (LNT) 2 mg in 20% glucose sol. 20 ml i.v./wk was combined with Teg sp 1,000 mg/day from May 13, 1987. Teg sp was reduced to 1,000 mg/2 days from June of the same year, and since then the same therapy of Teg + LNT has been continuing even now. Serum AFP values showing 150 X 10(4) ng/ml at maximum were decreased down to less than 20 ng/ml 13 months after this therapy (total doses: Teg ca. 250 g, LNT 108 mg), remaining still normal. Marked reduction in the size of the lesion (PR) by the therapy has also been proved by the body CT. His PS is now in grade 0. Although in this case the initial steep decline in AFP values was possibly brought about by TAE, the successive antitumor effect indicated by persistent low AFP values may have been mainly due to Teg + LNT. Collection of data on the therapy is needed to clarify this point.