Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.     

Topical anti-inflammatory activity of dianemycin isolated fromStreptomyces sp. MT 2705-4

In order to develop new anti-inflammatory agents having different action mechanisms compared with nonsteroidal and steroidal anti-inflammatory drugs, the culture broths of various actinomycetes isolated from soil were screened using anin vivo mouse ear edma assay and one strain (Streptomyces sp. MT 2705-4: KCTC 8651P) was selected. Activity-guided purification led to the isolation of a polyether compound, dianemycin. Topically, dianemycin showed a potent anti-inflammatory activity in mouse ear edema induced by croton-oil or arachidonic acid. ED(50) value of dianemycin was found to be 0.8 mg/ear compared to 0.4 mg/ear of prednisolone in croton-oil ear edema. However, dianemycin did not show the inhibitory activity in UV-erythema and delayed hypersensitivity reaction. These results indicate that dianemycin is a potential topical anti-inflammatory agent.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

Cellular Delivery of Nucleoside Diphosphates: A Prodrug Approach

Purpose. This study is concerned with cellular delivery/generation of 2′-azido-2′-deoxyuridine and -deoxycytidine diphosphate (N₃UDP or N₃CDP), potent inhibitors of ribonucleotide reductase. It characterizes the phosphorylation steps involved in the conversion of 2′-azido-2′-deoxyuridine (N₃Urd) and 2′-azido-2′-deoxycytidine (N₃Cyd) to the corresponding diphosphates and explores a prodrug approach in cellular delivery of the inhibitor which circumvents the requirement of deoxynucleoside kinases. Methods. Cell growth of CHO and 3T6 cells of known deoxycytidine kinase level was determined in the presence of N₃Urd and N₃Cyd. Activity of ribonucleotide reductase was determined in the presence of the azidonucleosides as well as their mono- or di-phosphates in a Tween 80-containing permeabilizing buffer. A prodrug of 5′-monophosphate of N₃Urd was prepared and its biological activity was evaluated with CHO cells as well as with cells transfected with deoxycytidine kinase. Results. N₃Urd failed to inhibit the growth of both cell lines, while N₃Cyd was active against 3T6 cells and moderately active against CHO cells. These results correlate with the deoxycytidine kinase levels found in the cells. Importance of the kinase was further established with the finding that the nucleoside analogs were inactive as reductase inhibitors in a permeabilized cell assay system while their mono- and di-phosphates were equally active. The prodrug was active in cell growth inhibition regardless of the deoxycytidine kinase level. Conclusions. The azidonucleosides become potent inhibitors of the reductase by two sequential phosphorylation steps. The present study indicates that the first step to monophosphate is rate-limiting, justifying a prodrug approach with the monophosphate.     

Inhibitory effect of the root ofCoptis japonica on catecholamine biosynthesis in PC12 cells

The effect of the root ofCoptis japonica (COPT), both the dichloromethane soluble (CH₂Cl₂) and insoluble (H₂O) fractions, on catecholamine contents and tyrosine hydroxylase (TH) activity in PC12 cells was investigated. CH₂Cl₂ and H₂O fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a concentration of 40 μg/ml in medium: the H₂O fraction provided a greater inhibitory effect. The TH activity was reduced by the treatment of COPT (H₂O fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.     

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

ＳＥＡＲＣＨＦＯＲＨＥＲＰＥＳＳＩＭＰＬＥＸＶＩＲＵＳＴＹＰＥ２（ＨＳＶ－２）ＡＮＤＨＵＭＡＮＰＡＰＩＬＬＯＭＡＶＩＲＵＳ（ＨＰＶ）ＩＮＴＨＥＮＯＲＭＡＬＡＮＤＡＢＮＯＲＭＡＬＣＥＲＶＩＣＡＬＳＡＭＰＬＥＳＺｈａｎｇＷｅｉ;张伟;ＪｉｎＳｈｕｎｑｉａ...     

Multiple effects on drug-sensitivity, genome stability and malignant potential by combinations of h-ras, C-myc and mutant p53 gene overexpression

Activation of specific oncogenes and inactivation of tumor suppressor genes play major roles in mechanisms leading to neoplastic transformation. The potential involvement of these genes in determining genome stability is an important issue. To examine the relationships between altered oncogene expression and the effects on genome stability, we have investigated the drug sensitivity properties of mouse 10T1/2 fibroblasts transfected with combinations of H-ras, c-myc and the proline 193 mutant form of p53. The relative colony forming efficiencies of these cells were investigated in the absence or presence of various concentrations of the chemotherapeutic agents, methotrexate, N-(phosphonacetyl)-L-aspartate (PALA) or hydroxyurea. The effects of altered oncogene expression were found to be drug and locus specific, and to lead to increased drug resistance (e.g. H-ras transfectants were significantly resistant to methotrexate or PALA), decreased drug resistance (e.g. H-ras/-myc transfectants were significantly less resistant to PALA or hydroxyurea than H-ras transfected cells), or to no significant change in drug sensitivity (e.g. H-ras transfected cells were not significantly different in sensitivity to hydroxyurea than non-transfected cells). Gene amplification was an important but not the only mechanism for drug resistance. Cells that were transfected with p53 (H-ras/p53 or H-ras/c-myc/p53) exhibited the greatest drug resistance properties with all three chemotherapeutic agents, in keeping with the important role of p53 in DNA repair and DNA amplification mechanisms. Although both H-ras/p53 and H-ras/c-myc/p53 groups exhibited very similar genome stability characteristics as determined by drug sensitivity results, they were significantly different in their abilities to produce transformed foci in vitro and lung metastases in vivo. The H-ras/c-myc/p53 transfected cells formed significantly higher numbers of transformed foci and exhibited a greater malignant potential. These results are consistent with observations that H-ras expression directly correlates with malignant potential, and that H-ras/c-myc/p53 transfected cells have higher H-ras expression than H-ras/p53 transfected cells. Alterations in genomic integrity through changes in onocogene expression play important roles in mechanisms determining drug sensitivity; in addition to genome destabilization, other events are critically involved in regulating transformed and malignant characteristics.     

舌脉诊法考

舌脉诊法主要观察舌腹面血管系统的变化,为我国所特有。《内经》首载舌脉刺血治疟、狂、忧虑无言、心病等,以盛即粗张为施术指征。晋以后发展为诊法,葛洪用于虏黄,巢元方用于噤黄与五色黄病情深浅判断,《医门方》用于预测难产母子吉凶,陈自明编《产难生死诀》以广流传。本法继承了络脉诊法的理论,重视络脉形色观察,以盛与青黑为逆,从血瘀痰郁辨证。明清未见明显发展,但作为奇穴刺血治舌肿、喉闭、黄疸并未中断,周学海发挥刘守真“玄府论”,倡舌细络瘀血说,难能可贵的是与今微循环障碍理论符合。１９６４年张赞臣再倡,研究者日众,临床多而基础少,认为对瘀证及肿瘤、肝病、肺心病有较高诊断价值。     

二甲苯对不同年龄大鼠脑组织形态学及神经细胞凋亡的影响

目的　探讨年龄对二甲苯神经毒作用的影响。方法　采用 Ｈ Ｅ 染色法和 Ｔ Ｕ Ｎ Ｅ Ｌ 技术对不同月龄大鼠的脑组织病理形态学和神经细胞凋亡情况进行了研究。结果　二甲苯５００ ｍ ｇ／ｋｇ 染毒后,２ 月龄组较８ 月龄组大鼠脑组织形态学改变相对严重,２ 月龄组染毒大鼠神经细胞凋亡的发生率为（１ ．５３ ±１ ．０６） 个／ 视野,明显高于同龄对照组的（０ ．９３ ±０ ．７５） 个／ 视野, Ｆ＝ １２ ．６５９ ６ , Ｐ＜ ０ ．００１ ;８ 月龄组染毒大鼠的神经细胞凋亡率为（１ ．６５ ±１ ．１１） 个／ 视野,明显高于同龄对照组的（１ ．１５ ±１ ．０７） 个／ 视野, Ｆ＝ ６ ．２６３ ３ , Ｐ＜ ０ ．０５ 。结论　低龄大鼠对二甲苯的神经毒作用更为敏感