Ovalbumin modified by gamma irradiation alters its immunological functions and allergic responses

It is well known that gamma (gamma)-ray irradiation results in the alteration of biological function of bioactive materials such as proteins, saccharides and lipids. In this study the effect of gamma-irradiation on the chemical and immunological property of an allergen, ovalbumin (OVA), was investigated. Irradiation of more than 10 kGy resulted in the alteration of the structure of OVA. However, OVA treated with 10 kGy irradiation (10 kGy-OVA), but not 100 kGy-OVA, fully maintained immunological reactivity to a monoclonal antibody specific to the intact allergen (clone 14). Mice immunized with 10 kGy- as well as 100 kGy-OVA showed significantly lower antibody response to the allergen than those with intact OVA in a gamma-ray dosage-dependent manner. Especially immunization of both 10 kGy- and 100 kGy-OVA induced a significant decrease of OVA-specific IgE. Splenocytes of mice immunized with irradiated OVA showed a significant reduction in OVA-specific T cell proliferation and the secretion of Th1-type (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-6). The expression of T cell activation markers such as CD25 and CD44 was also down-regulated in T cells of mice immunized with irradiated OVAs. These results suggest that gamma-ray irradiation of OVA suppress humoral and cellular immune responses specific to the allergen OVA, and the modification method with gamma-irradiation may be available for the control of allergy.     

Anti-HCV bioactivity of pseudoguaianolides from Parthenium hispitum

Five new (1-5) and four known (6-9) C14-oxygenated 1alpha-hydroxy-11(13)-pseudoguaien-6beta,12-olides with potent inhibition of hepatitis C virus (HCV) replication were obtained from Parthenium hispitum via high-throughput natural product chemistry methods. A semipreparative HPLC system was used to purify these compounds. The miniaturization of the structure elucidation and dereplication for the mass-limited samples were performed primarily utilizing a capillary-scale NMR probe. Compounds 2-4 were found to possess in vitro anti-HCV activity in the subgenomic HCV replicon system containing luciferase reporter with significant inhibition above 90% at 2 microM concentration.     

HMCO5, herbal extract, inhibits NF-kappaB expression in lipopolysaccharide treated macrophages and reduces atherosclerotic lesions in cholesterol fed mice

HMCO5 is a herbal extract which comprises of eight different herbs. We studied whether this extract has anti-atherosclerotic effects. In lipopolysaccharide (LPS) stimulated RAW264.7 cells, HMCO5 inhibited NF-kappaB activation as well as iNOS promoter activity, inhibited the secretion of TNF-alpha and IL-1beta, and directly inhibited the intracellular accumulation of reactive oxygen species. ApoE knock-out mice fed a high-fat high-cholesterol diet with HMCO5 for 10 weeks showed a significant reduction in atherosclerotic lesions. A notable finding was the preservation of the smooth muscle cell layer in the media of aorta in the HMCO5 co-treated mice. HMCO5 treated mice did not show significant decrease in serum level of cholesterol. These results suggest that HMCO5 has anti-atherosclerotic effects which in part may be attributable to the inhibition of production of NF-kappaB dependent pro-inflammatory cytokines.     

Cementless alumina-on-alumina total hip arthroplasty in patients younger than 50 years: a 5-year minimum follow-up study

Sixty-seven patients (78 hips) who were younger than 50 years underwent cementless total hip arthroplasty using a porous-coated acetabular cup, an alumina liner, a 28-mm alumina head, and a proximally porous-coated femoral stem. One patient (1 hip) died and 2 patients (3 hips) were lost to follow-up. The remaining 64 patients (74 hips) were followed for 5 to 6 years. Their mean age at the index operation was 37 years. The mean Harris hip score was 94 points at the time of final follow-up. Four patients (4 hips) had mild thigh pain. All acetabular and femoral components were bone-ingrown, and neither pelvic nor femoral osteolysis was identified. No fracture of the ceramic liner or head was identified. Wear of the ceramic components was undetectable in 27 hips in which measurement was possible.     

Pharmacokinetics of DA-7218, a new oxazolidinone, and its active metabolite, DA-7157, after intravenous and oral administration of DA-7218 and DA-7157 to rats

DA-7218 (a prodrug of DA-7157), a new oxazolidinone, was hydrolysed via phosphatase to form its active metabolite, DA-7157, in rats. The pharmacokinetic parameters of DA-7218 and DA-7157 were evaluated after intravenous (5, 10 and 20 mg kg(-1)) and oral (20, 50 and 100 mg kg(-1)) administration of DA-7218 to rats. DA-7218 and DA-7157 exhibited dose-proportional pharmacokinetics after both intravenous and oral administration of DA-7218 to rats. The stability of DA-7218 and DA-7157, blood partition of DA-7157, and the plasma protein binding of DA-7157 were also evaluated. DA-7218 was unstable in rat blood, plasma, bile and liver homogenates, but DA-7157 was stable, suggesting that DA-7218 is hydrolysed via phosphatase. DA-7157 rapidly reached equilibrium between plasma and blood cells, and the mean equilibrium plasma-to-blood cells ratio was 3.18, indicating that binding of DA-7157 to blood cells was not considerable. The protein binding of DA-7157 in fresh rat plasma was 93.4%.     

Genetic polymorphism of <Emphasis Type="Italic">XRCC3</Emphasis> Thr<Superscript>241</Superscript>Met and breast cancer risk: case-control study in Korean women and meta-analysis of 12 studies

To evaluate the relationship of genetic polymorphism in XRCC3 Thr²⁴¹Met and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995–2001. Information on demographic characteristics and other information were collected by interviewed questionnaire. Genetic polymorphisms of XRCC3 Thr²⁴¹Met (C > T) was determined by single base extention assay. The frequency of Thr/Thr, Thr/Met, and Met/Met genotype were 89.4, 10.4, 0.2% in cases and 92.3, 7.7, 0.0% in controls, respectively. Genotype distribution in controls fit well to the Hardy–Weinberg equilibrium (P = 0.74). XRCC3 codon 241 Thr/Met or Met/Met genotype moderately increased the risk of breast cancer (OR = 1.4, 95% CI: 0.87–2.33), but not significant in this study. In the results of meta-analysis using twelve reports, however, Thr/Met or Met/Met genotype increased the risk of breast cancer (OR = 1.08, 95%CI: 1.00–1.17). In conclusion, although the genetic polymorphism of XRCC3 Thr²⁴¹Met was unlikely to have a substantial overall association in Korean women, the meta-analysis of studies, including ours, provided that Thr/Met and Met/Met was weakly increased the risk of breast cancer compare to Thr/Thr genotype.