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.     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

A sensitive and simplified HPLC analysis for the determination of fluconazol in human plasma

A sensitive and simplified HPLC assay of fluconazol is described. The calibration curve of fluconazol in plasma ranging 0–10 μ g/ml was linear with the correlation coefficients of 0.9900. The limit of detection was 0.3 μ g/ml. The average recovery of the drug was 89.1±9.05%. After oral administration of single dose(150mg) of fluconazol in man, C_max and T_max were 3 μg/ml and 4hr., respectively.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.     

Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis

Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.