抗肿瘤药物研究Ⅰ:去甲斑蝥素氨基酸衍生物的合成与抗癌活性

In order to search for new compounds with higher anti-cancer activities and lower toxicities, 19 amino acid derivatives of norcantharidin, of which 16 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that 2-(syn-exo-7-oxabicyclo [2. 2. 1] heptane-2, 3-dicarboxylic imido)-N-phenyl glutaramic acid exhibited a fairly apparent inhibitory activity against human-hepatoma cells in vitro (inhibitory rate 39.4% at 0.025 μtmol/ml).     

Abortifacient Potential of Aqueous Extract of Senna alata Leaves in Rats

Objective To study the abortifacient activity of aqueous extract of Senna alata leaves in female Wistar rats.Methods Pregnant rats weighing 143.65 ± 13.11 g were completely randomized into 5 groups（A-E）.Rats in group A（negative control） were orally administered,once daily with 0.5 ml of distilled water on days 10-18 post-coitum while those in groups B,C,D,and E were treated exactly like the negative control except they received the same volume containing 2.85 mg/kg body weight of mifepristone（group B,reference drug）,250,500 and 1 000 mg/kg body weight of the extract respectively（groups C-E）.Results Phytochemical screening of the extract showed positive results for saponins（1.22%）,flavonoids（1.06%）,cardiac glycosides（0.20%）,cardenolides and dienolides（0.18%）,phenolics（0.44%） and alkaloids（0.52%）.Respiratory distress,salivation,diarrhoea,changes in the appearance of hair as well as maternal mortality were not observed at any time during the exposure period except in the mifepristone-treated animals where there was episode of diarrhoea and tiredness.The extract significantly reduced（P〈0.05） the number of life foetus,weight and survival ratio of the foetus,numbers of implantations and Corpora lutea,implantation index,progesterone,prolactin,estradiol,follicle stimulating and luteinizing hormones whereas the number of dead foetus,number and percentage of rats that aborted,percentage vaginal opening,resorption index,pre-and post-implantation losses increased significantly.In addition,mifepristone-treated animals produced resorption index that compared well with the distilled water control.There was also no dead or life foetus and serum progesterone concentration was increased in the animals treated with mifepristone.All cases of abortion were accompanied with vaginal bleeding.Although,the final weight of the rats increased significantly,the feed and water intake were not significantly altered in all the treatment groups.The weight of the uterus,uterine-body weight ratio,length of the right uterus horn and uterine cholesterol decreased significantly in all the treatment groups.The uterine alkaline phosphatase activity and glucose concentration increased in only the extract-treated animals whereas mifepristone decreased the uterine alkaline phosphatase activity and glucose content of the animals.Conclusion This study has provided evidence to the age-long claim of S.alata leaves in ＂washing the uterus＂.The abortifacient properties were most pronounced at 500 and 1 000 mg/kg body weight of the extract and were similar to the animals treated with 2.85 mg/kg body weight of mifepristone.Hormonal influence,changes in implantation site,estrogenicity and uterogenicity are suggested as possible mechanism of abortifacient activity of aqueous extract of S.alata leaves.Overall,the extract may be used as an abortifacient especially at 500 and 1 000 mg/kg body weight and therefore not safe for consumption as oral remedy during pregnancy.     

p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.     

Temperature-dependent effects of EDTA on the membrane glycoprotein IIb- IIIa complex and platelet aggregability

In agreement with previous studies, we observed that incubation of washed human platelets with EDTA at 37 degrees C for short periods caused an irreversible loss of their aggregation response to adenosine diphosphate and markedly diminished their capacity to bind fibrinogen. AP-2 is a monoclonal antibody that reacts with a determinant specific to the glycoprotein (GP) IIb-IIIa complex. We now report that in a direct binding assay, the number of sites for AP-2 on platelets incubated with EDTA at 37 degrees C fell to approximately 30% of those present on control platelets. This effect of EDTA was not observed at room temperature. Analysis of the treated platelets by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed normal amounts of GP IIb and GP IIIa. However, studies using crossed immunoelectrophoresis with 125I-AP-2, 125I-Tab (anti-GP IIb), or 125I- AP-3 (anti-GP IIIa) in intermediate gels showed that at 37 degrees C, EDTA was inducing an irreversible change in GP IIb-IIIa complexes. A reduction in size and probable dissociation of the GP IIb-IIIa precipitate was accompanied by the appearance of precipitates having the characteristics of those given by free GP IIb and free GP IIIa and the location of a major new cathodal precipitate, which bound Tab and AP-3 but not AP-2. Membrane modifications associated with the loss of antigenic determinants on GP IIb-IIIa may explain EDTA-induced loss of platelet aggregability at 37 degrees C.     

Sexual dysfunction in dermatological diseases

Decrease or loss of sexual function in many chronic diseases has recently attracted significant attention owing to its impact on quality of life. Generic and disease-specific quality-of-life questionnaires measure changes in work, school, social life and emotional status regarding the disease and its treatment. Specific questionnaires have been designed to evaluate changes in sexuality and sexual function. Sexual dysfunction, especially female sexual dysfunction, in different diseases became a popular and important health concern in recent years. There are a lot of studies about sexual dysfunction in the areas of other specialities of medicine, but there are only a few studies in dermatological diseases. In this paper, sexual dysfunction and the studies performed about this subject in dermatology will be reviewed.

Conflict of Interest

None declared.     

Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.