Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers.

To improve the drug permeation into and/or across the skin, essential oils extracted from Alpinia oxyphylla (AO) were evaluated using in vitro and in vivo permeation techniques with Wistar rats as the animal model. Hydrocarbons and oxygenated sesquiterpenes were the major components in the lower-polarity fraction (AO-1) and higher-polarity fraction (AO-2), respectively. Permeation of indomethacin was significantly enhanced after treatment with AO-1 and AO-2 in the in vitro and in vivo studies. AO-2 generally showed a higher ability to promote drug permeation compared to AO-1. The increment of skin/vehicle partitioning may be the predominant mechanism for this enhancing activity. Both transepidermal water loss (TEWL) and colorimetric evaluation showed limited irritation to skin by AO essential oils at the macroscopic level. Human skin fibroblasts were used to investigate the in vitro screening of skin toxicity. AO-1 slightly increased prostaglandin E(2) (PGE(2)) formation from skin fibroblasts. A striking result was observed with AO-2, which greatly inhibited the release of PGE(2). Moreover, both AO essential oils had no statistically significant effect on PGE(2) release by human lung epithelial cells. The results of this study indicate that skin disruption and inflammation do not necessary correspond to the enhancing efficiency of the enhancers tested.     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

Flavonoids from the leaves ofRhododendron brachycarpum

The flavonoids isolated from the leaves ofRhododendron brachycarpum, were identified as quercetin, avicularin, quercitrin and hyperin.     

Synthesis of polymers containing pseudohalide groups by cationic polymerization, 13. “Living” polymerization of 2-methylpropene initiated by the system 1,4-bis(1-azido-1-methylethyl)benzene/BCl3/dimethyl sulfoxide

Polymerizations of 2-methylpropene (MP) initiated by the system 1,4-bis(1-azido-1-methylethyl)benzene (DAMEB)/BCl₃ in the presence of DMSO were carried out by “all monomer in” (AMI) technique at ?70°C in CH₂Cl₂ solution. FT-IR, ¹H NMR and SEC analyses of polymers (PMP) showed that the M _n versus weight of PMP plot is a straight line without intercept and azide F_n3 and aromatic ring F_? functionalities are close to the theoretical values of 2 and 1, respectively. A polymerization of MP initiated by the system α,ω-diazido-PMP/BCl₃/DMSO led to a final poly(2-methylpropene) (PMP) with an increase of M _n corresponding to the amount of MP introduced and presenting the same functionalities F_N3 and F_? as the starting PMP. These results indicate that the polymerization system MP/DAMEB/BCl₃/DMSO is a “living” one, because in an acceptably large range of molecular weight (M _n < 50000) the Mayo plot 1/DP versus 1/DP ₀ is a straight line. The intercept gives k_trM/k_p = 4 · 10^?5, showing the transfer reaction proceeds at very low rate.     

Isolation of hepatic drug metabolism inhibitors from the seeds ofMyristica fragrans

The hexane extract from Nutmeg, the seed ofMyristica fragrans significantly inhibited hepatic drug-metabolizing enzyme activity. Through systematic fractionation by SiO₂ column and vacuum liquid chromatography monitoring by bioassay, three components, myristicin, (I), licarin-B(II) and dehydrodiisoeugenol(III) were isolated as active principles. Compounds II and III, with a single treatment (200 mg/kg, i.p.) showed not only a significant prolongation of hexobarbital-induced sleeping time but also a significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds I and II provoked a sleep episode at a subhypnotic dose of HB, suggesting that they posses CNS-depressant properties.     

Flavonoids ofElscholtzia cristata

Apigenin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and linarin were isolated fromElscholtzia cristata (Labiatae).     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Relationship between normal heart size and body indices in Korean

We provided a curve-fit equation to predict the normal heart weight (g) in Koreans by examining 422 autopsies (215 males and 207 females, from newborn to age 77 yr) who were relatively in good general condition. Heart weight was well correlated with body surface area (m2), body weight (kg), and body height (cm) but poorly with age in both sex. Heart weight progressively increased from birth to the earlier 3rd and 4th decades in male and female, respectively, and then gradually decreased; mean heart weight of all age group was greater in male than in female and significantly different from birth to 4th decade. In both sex, heart weight exponentially increased in accordance with the increase of body height, body weight, and body surface (in male, heart weight=0.00312 x body height(2.239), r2=0.750, p<0.0001; in female, heart weight=0.00443 x body height(2170), r2=0.781, p<0.0001; in male, heart weight=9.22 x body weight(0.853), r2=0.770, p<0.0001; in female, heart weight=9.00 x body weight0.855, r2=0.820, p<0.0001; in male, heart weight=155.18 x body surface area1.290, r=0.808, p<0.0001; in female, heart weight=124.13 x body surface area1.242, r=0.834, p<0.0001). These results indicate that heart weight is better correlated with body surface area than with body weight; however, body weight should be a better determinant of a predicted heart weight, since body surface area is entirely dependent on body height and body weight.     

Detection of antibodies to human immunodeficiency virus by latex agglutination with recombinant antigen.

Recombinant human immunodeficiency virus (HIV) env antigen was attached to polystyrene particles, and these complexes were used to develop the first latex agglutination assay for antibodies to HIV. A total of 95 positive and 116 negative human serum samples were assayed for antibodies to HIV by latex agglutination, and results were compared with those of a commercial enzyme immunoassay. Latex agglutination was also compared with, and found to be completely concordant with, Western blot (immunoblot) analysis with virion antigens.