Cytotoxic saponins from the root ofDipsacus asper wall

Cytotoxic activitiy of seven hederagenin saponins isolated from the root of Dipsacus asper were investigated in vitro against L1210, HL-60 and SK-OV-3 tumor cell lines by the MTT method. 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl hederagenin (2), 3-O-beta-D-xylopyranosyl-(1-->3)-alpha-L-Rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl hederagenin (6) and 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl hederagenin (7) exhibited the potent cytotoxicity against the three tumor cell lines with IC50 values ranging from 4.7 to 8.7 microg/mL, with the exception of compound 7, which exhibited weak cytotoxic activity against SK-OV-3 (IC50 22.5 microg/mL). Other compounds did not exhibit any cytotoxic activity (IC50 > 30 microg/mL).     

Inhibitory effect of whole bee venom in adjuvant-induced arthritis

The aim of this study was to assess the inhibitory effect of whole bee venom (BV) on adjuvant-induced arthritis in the rat. Rats were divided into pre-apitherapy, post-apitherapy and control experimental groups. The pre-apitherapy group was subcutaneously stung with a honeybee (Apis mellifera L.) and the control group was subcutaneously injected with 0.1 ml of physiological saline solution one day prior to complete Freund's adjuvant (CFA) injection. The post-apitherapy group was subcutaneously stung with a honeybee on day 14 after CFA injection. When arthritis had developed in the rat, the post-apitherapy group was subcutaneously administered whole BV every other day for a further 14 days. Clinical signs, hematological values and radioglogical features were observed during the entire experimental period. In the pre-apitherapy group, the development of inflammatory edema and polyarthritis was inhibited. Significant differences in lameness score, hind paw edema volume and radiological features were observed between control and pre-apitherapy rats. White blood cell counts indicated that the degree of leucocytosis was significantly different between the pre-apitherapy and control groups (p < 0.01). Inflammatory edema, polyarthritis and bone change into the right hind paw were effectively inhibited in pre-apitherapy rats during the two-week period post-CFA injection. In conclusion, whole BV was found to inhibit arthritic inflammation and bone changes in the rat. This may be an alternative treatment for arthritis in humans.     

Hepatoprotective effect of 20(S)-ginsenosides Rg3 and its metabolite 20(S)-ginsenoside Rh2 on tert-butyl hydroperoxide-induced liver injury

To evaluate the hepatoprotective effect of Red Ginseng (RG), we isolated a main constituent 20(S)-ginsenoside Rg3 from RG, and its metabolite 20(S)-ginsenoside Rh2 by human intestinal microflora, and investigated their hepatoprotective activities in tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity of HepG2 cells and mice. When HepG2 cells were treated with t-BHP, its cytotoxicity was significantly increased. 20(S)-Ginsenoside Rh2 potently protected its cytotoxicity, but 20(S)-ginsenoside Rg3 weakly protected it. Intraperitoneally and orally administered 20(S)-ginsenoside Rh2 to t-BHP-injured mice significantly inhibited the increase of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Orally administered 20(S)-ginsenoside Rg3 also showed the inhibition against the increase of ALT and AST of t-BHP-induced mice. However, intraperitoneally administered 20(S)-ginsenoside Rg3 could not inhibit the elevation of serum ALT and AST activities. These results suggest that 20(S)-ginsenoside Rg3 a main component of RG may be a prodrug for hepatotoxicity.     

Antiinflammatory activity of astilbic acid from Astilbe chinensis

This study examined the effect of astilbic acid (3beta,6beta-dihydroxyolean-12-en-27-oic acid), which is a herbal medicine isolated from Astilbe chinensis. Astilbic acid inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C4 (LTC4) generation in bone marrow-derived mast cells in a concentration-dependent manner with an IC50 value of 2.1 microM. In addition, astilbic acid was tested in a rat passive cutaneous anaphylaxis (PCA) reaction assay by administering 10 to 50 mg/kg i.p. Astilbic acid dose dependently inhibited the PCA reaction, which was activated by anti-dinitrophenyl (DNP) IgE. Furthermore, this compound inhibited mouse acetic acid-induced writhing (47-62% inhibition at 0.4-50 mg/kg) after being administered orally, while aspirin (200 mg/kg) showed 62% inhibition. These results suggest that astilbic acid may be beneficial in regulating various inflammatory processes.     

Preoperative plasma fibrinogen levels in gastric cancer patients correlate with extent of tumor

BACKGROUND/AIMS: The aim of the present study was to investigate the relationship between the preoperative plasma fibrinogen level and the extent of tumor involvement in gastric cancer patients. METHODOLOGY: Preoperative plasma fibrinogen levels of 354 patients who underwent gastric cancer surgery were quantified using an immunoassay. The relationships between the plasma fibrinogen level and other prognostic variables (tumor size, macroscopic and histological type, depth of tumor invasion, presence of lymph node involvement and distant metastasis) were then examined using univariate and multivariate linear regression analyses. RESULTS: The plasma fibrinogen level was significantly lower in patients with early gastric cancer than in those with advanced gastric cancer (312+/-6.7 vs. 361.9+/-97.0 mg/mL, p<0.001). A significant relationship existed between the preoperative fibrinogen levels and the presence of metastatic lymph nodes (320+/-78.6 vs. 352.6+/-94.1 mg/mL, p=0.001) and distant metastasis (338.2+/-89.5 vs. 396.9+/-128.3 mg/mL, p=0.013). Size of the tumors and depth of tumor invasion could predict elevated fibrinogen levels positively in both the univariate regression and multivariate linear regression analyses. CONCLUSIONS: These data suggest that the plasma fibrinogen level is a clinically important and useful marker of the extent of tumor progression in gastric cancer.     

Factors associated with attention deficit/hyperactivity disorder among US children: Results from a national survey

ABSTRACT: BACKGROUND: The purpose of this study was to investigate the association between Attention Deficit/Hyperactivity Disorder (ADHD) and various factors using a representative sample of US children in a comprehensive manner. This includes variables that have not been previously studied such as watching TV/playing video games, computer usage, family member's smoking, and participation in sports. METHODS: This was a cross-sectional study of 68,634 children, 5-17 years old, from the National Survey of Children's Health (NSCH, 2007-2008). We performed bivariate and multivariate logistic regression analyses with ADHD classification as the response variable and the following explanatory variables: sex, race, depression, anxiety, body mass index, healthcare coverage, family structure, socio-economic status, family members' smoking status, education, computer usage, watching television (TV)/playing video games, participation in sports, and participation in clubs/organizations. RESULTS: Approximately 10% of the sample was classified as having ADHD. We found depression, anxiety, healthcare coverage, and male sex of child to have increased odds of being diagnosed with ADHD. One of the salient features of this study was observing a significant association between ADHD and variables such as TV usage, participation in sports, two-parent family structure, and family members' smoking status. Obesity was not found to be significantly associated with ADHD, contrary to some previous studies. CONCLUSIONS: The current study uncovered several factors associated with ADHD at the national level, including some that have not been studied earlier in such a setting. However, we caution that due to the cross-sectional and observational nature of the data, a cause and effect relationship between ADHD and the associated factors can not be deduced from this study. Future research on ADHD should take into consideration these factors, preferably through a longitudinal study design.     

Anti-adhesive functions of CD43 expressed on colon carcinoma cells through the modulation of integrins

CD43 has conflicting roles in both pro- and anti-adhesive function in cell-to-cell adhesion in hematopoietic cells. We examined the role of CD43 glycoprotein in a colorectal carcinoma cell line. We expressed human CD43 antigen on HT-29 cells, a colon adenocarcinoma cell line, and compared the adhesion to the extracellular matrix with that of mock-transduced cells in vitro. CD43 expression inhibited the adhesion to extracellular matrix, such as collagen type IV and laminin. As the expression of β1 integrin was downregulated in CD43-expressing HT-29 cells, the anti-adhesive effect of CD43 might be implicated in its expression. Our findings suggest that the anti-adhesive function of CD43 in colon carcinoma cells plays a role in the tumorigenesis and metastasis of colorectal carcinoma cells.     

Clinical, biochemical, and genetic analysis of two korean patients with trichorhinophalangeal syndrome type I and growth hormone deficiency

Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant hereditary disorder characterized by sparse hair, bulbous nose, long philtrum, thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. TRPSI is caused by mutations in the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both patients (a 17-year-old-female and a 14-year-old male) had typical clinical findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7±0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH stimulation test, had a poor response with rhGH therapy and GH therapy was discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two mutations were found. Patient 1 had a heterozygous mutation c.2520dupT (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report Korean patients with mutation of TRPS1.     

A Korean patient with Morquio B disease with a novel c.13_14insA mutation in the GLB1 gene

Mutations in the GLB1 gene, which encodes acid β-galactosidase, can result in two disease phenotypes: GM1-gangliosidosis (MIM #230500) and Morquio B disease (Mucopolysaccharidosis type IVB, MIM #253010). Morquio B disease occurs much more infrequently than GM1-gangliodosis and is characterized by severe skeletal manifestations (dysostosis multiplex) without central nervous system involvement. Here, we report the first known Korean patient with Morquio B disease. A 7-year-old boy presented with severe progressive skeletal dysplasia including scoliosis, contractures of the elbows, xenu valgum, funnel chest, and trigger thumb requiring surgical intervention. The patient had normal neurological functions and mental status when evaluated by pediatric neurologists. The patient's urinary glycosaminoglycans, measured by the cetylpyridinium chloride (CPC) precipitation test, were 252.8 CPC unit/g creatinine (reference range < 175). Thin layer chromatography of urine showed a keratan sulfate band. Enzyme activity of β-galactosidase in leukocytes was 1.15 nmol/hr/mg protein (reference range 78.1-117.7; 1-1.5% of normal). The patient had compound heterozygous mutations of the GLB1 gene: c.13_14insA (p.L5HfsX29), which was reported in a patient with infantile GM1 gangliosidosis with the near-complete absence of enzyme activity, and c.367G>A (p.G123R), which is a novel frame-shift mutation. In summary, we report the first known Korean patient with Morquio B disease and a novel mutation (c.13_14insA of GLB1).