三氧化二锑诱导急性早幼粒细胞白血病细胞凋亡的研究

目的 研究锑剂三氧化二锑（Sb2O3)对早幼粒细胞白血病细胞株NB4凋亡的诱导作用，以寻求早幼粒细胞白血病治疗的新方法。方法 采用细胞生长曲线，形态学及硝基四氮唑蓝（NBT）还原试验，判定NB4细胞的生长，分化及功能。采用细胞周期分析和DNA电泳研究细胞凋亡。结果 Sb2O3能诱导早幼粒白血病细胞凋亡，且具有时间，剂量依赖性。结论 Sb2O3能有效地诱导早幼粒白血病细胞凋亡，提示锑剂诱导细胞半亡的疗法，有望成为临床治疗早幼粒细胞白血病的新方法。     

Consensus statement on the bio-safety of urinary-derived gonadotrophins with respect to Creutzfeldt-Jakob disease

Human transmissible spongiform encephalopathies (TSE) encompass a group of rare neurodegenerative diseases. In April 2004, a group of international experts and regulators met in Buenos Aires, Argentina, to review the safety and to reach consensus on the use of urinary-derived gonadotrophins with respect to TSE. Iatrogenic transmission of Creutzfeldt-Jakob Disease (CJD) from pituitary-derived gonadotrophins has been reported, no infectivity in urine has been demonstrated, and no definite cases of transmission via urine have been reported. It is currently not possible to monitor donor urine or finished product for the presence of prions. Therefore the assessment of risk has to be based on the likelihood of infection in urine, the source of the urine, and the capacity of the manufacturing process to remove any adventitious infection. Urine for the production of medicinal products should be obtained from sources that minimize the possible presence of materials derived from subjects suffering from human TSE. As no strong evidence for TSE infectivity in urine exists, it can be concluded that the risk of disease-generating prions and TSE infectivity being present in donor urine is low. Current evidence indicates that, with respect to the risk of TSE infection, urinary-derived gonadotrophins appear to be safe.     

Endocrinology: Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion

Mifepristone (600 mg) in combination with a prostaglandin hasbeen demonstrated to be a safe, acceptable alternative to vacuumaspiration for induction of abortion in the first 9 weeks ofpregnancy. However, the efficacy and side-effects of differentprostaglandins used in combination with mifepristone have notbeen assessed in a randomized trial. In this study, 800 womenseeking an abortion at gestational age 63 days amenorrhoea wererandomized to receive either 0.5 mg gemeprost by vaginal pessary(group I) or 600 µg misoprostol (group II) by mouth –48h after taking 200 mg mifepristone by mouth. The side-effectsand number of complete abortions were used as measures of efficacy.There was no significant difference in the rate of completeabortion between group I [96.7%; 95% confidence interval (CI)94.9–98.5%, n = 391] and group II (94.6%; 95% CI 92.3–96.9,n = 386). It was not possible to assess the outcome with certaintyin the remaining 23 women. However, there were significantlymore ongoing pregnancies in the women who received misoprostolthan in those who received gemeprost (nine versus one, P <0.01) and in eight of these 10 women the gestation was >49days. Fewer women in group II required analgesia than in groupI (48 versus 60%, P < 0.001) although the number requestingopiate was similar in each group (6.9 versus 5.2%, P > 0.4).The incidence of nausea and vomiting after misoprostol (47.8and 21.9% respectively) was higher (P < 0.001) than aftergemeprost (33.9 and 12% respectively). The incidence of infectionand heavy bleeding was low in both groups (<2%) and onlyone woman required blood transfusion. We conclude that the recommendeddose of mifepristone and gemeprost can be reduced without impairingclinical efficacy in pregnancies up to 63 days amenorrhoea.Misoprostol is a safe alternative prostaglandin but has a higherincidence of ongoing pregnancies especially at gestation after49 days amenorrhoea.     

珍珠层水溶性提取物对人骨髓基质细胞成骨性分化的诱导作用

目的:探讨珍珠层水溶性提取物(WSM)对人骨髓基质细胞的诱导作用。方法:原代培养人骨髓基质细胞,条件培养基和WSM分别作用于第3代细胞,对照组不加处理因素。倒置显微镜观察细胞在施加处理因素后的生长状态;采用钙钴法染色检测AKP表达;应用RT-PCR方法检测BMP-2等生长因子表达;应用茜素红染色检测骨髓基质细胞的矿化结节形成情况。结果:施加处理因素第7d,WSM组、条件培养基组的BMP-2表达水平较对照组明显增加;WSM组及条件培养基组TGF-β1表达量较对照组相比未见差异。施加处理因素第7d,WSM组及条件培养基组骨髓基质细胞AKP染色明显,与对照组相比差异显著。每高倍视野阳性细胞数,条件培养基组、WSM明显多于对照组,差异具有显著性(P<0.01);加入处理因素18d,条件培养基组可见典型红色钙化结节形成,WSM组也可见到钙结节形成,但没有条件培养基组典型,对照组偶有零星钙化结节形成。结论:WSM可以促进体外培养的人骨髓基质细胞成骨性分化进程,具有一定的骨诱导作用。     

Low incidence of antibody formation due to long-term interferon-α2c treatment of cancer patients

Summary In order to study the long-term immunogenicity of interferon-_2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-_2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-_2c antibodies. Due to long-term interferon-_2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 252 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-_2c. One hundred and sixty-three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon- preparations, the propensity of interferon-_2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-_2c molecule.Abbreviations ANB antiviral neutralization bioassay - CE competitive sandwich ELISA - EBI Ernst Boehringer Institut - IFN interferon     

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive Vβ8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of Vβ8⁺ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization to OVA, but shifted the immune response away from an immediate type response (IgE/IgG₁) to IgG_2a, IgG_2b and IgG₃. Although both protocols of SEB treatment did not lead to a major deletion of the Vβ8 T cell population, they did reduce the proliferative response of Vβ8⁺ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive Vβ8 T cells.     

针刺对多囊卵巢综合征大鼠卵巢TGF-α、EGFR表达的影响

目的:研究针刺对多囊卵巢综合征(PCOS)大鼠卵巢转化生长因子α(TGF-α)、表皮生长因子受体(EGFR)表达的影响,探讨针刺促排卵的作用机制。方法:24日龄雌性大鼠颈背部皮下注射脱氢表雄酮(DHEA)的油溶液制作(PCOS)模型,对照组同期皮下注射油剂。PCOS大鼠随机分为模型组和针刺组。模型组不作处理,针刺组大鼠从80日龄起针刺关元、中极、双侧三阴交、双侧子宫穴,1次/天,15min/次,连续6周。治疗结束后各组大鼠断头处死,迅速取血并分离血清,-20℃冰箱保存,待测性激素水平。摘取双侧卵巢,称重,4%多聚甲醛固定,作HE染色和免疫组织化学染色。结果:与模型组相比,针刺组卵巢湿重、卵巢TGF-α、EGFR表达及血清睾酮(T)、雌二醇(E2)水平均显著降低(P<0.01),而卵泡刺激素(FSH)、黄体生成素(LH)、孕酮(P4)水平差异无统计学意义(P>0.05)。结论:针刺能显著降低PCOS大鼠卵巢TGF-α及EGFR的表达,抑制TGF-α对卵巢和激素合成的作用,改善PCOS大鼠多囊样变和高雄激素血症,促进排卵。     

Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility

The aim of this prospective randomized controlled study wasto determine the possible role of ovulation induction with intrauterineinsemination (IUI) in the treatment of unexplained infertility.A total of 100 patients were randomized to receive ovulationinduction with or without IUI. All patients were treated withlong-course gonadotrophinreleasing hormone analogue (GnRHa),starting in the luteal phase, and exogenous follicle stimulatinghormone (FSH) to induce follicular growth. Ovulation was inducedusing human chorionic gonadotrophin and timed intercourse (TI)was advised 24–48 h later or IUI was effected 36—48h later. Both the cycle fecundities (21.8 and 8.5%) and thecumulative ongoing pregnancy rates after three cycles (42 and20%) were significantly higher (P < 0.03) in the IUI groupthan in the TI group respectively. This is a clear indicationthat ovulation induction with IUI is an effective treatmentmethod for unexplained infertility, but ovulation inductionwith TI has a negligible impact in this large group of patients.     

Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin

A total of 31 clomiphene citrate/human menopausal gonadotrophin(HMG)/human chorionic gonadotrophin (HCG)-stimulated cyclesin 28 patients were investigated to determine the fate of eachof the matured follicles. A standard stimulation regimen wasadhered to, and ultrasound as well as hormonal monitoring wasperformed. All follicles were measured by vaginal ultrasoundat –12, +35 and +45 h relative to HCG administration andat 7 days after HCG administration. Of the 220 follicles, 107(48.6%) ruptured. The number of ruptured follicles per cyclewas correlated with the mid-luteal progesterone concentration(r = 0.63, P = 0.0005). The probability of follicular rupturewas related to follicular diameter at 12 h before HCG administration;6% of follicles <12 mm in diameter ruptured compared with87% of follicles 18–19 mm. A complete luteinized unrupturedfollicle (LUF) syndrome was observed in six cycles (20%). Inthese cycles, follicular growth and oestradiol, progesterone,luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations at 12 h before HCG administration were similarto those in cycles with follicular rupture. However, mid-lutealprogesterone concentrations were lower in complete LUF cycles(46.97 ± 8.95 nmol/1 versus 108.74 ± 12.27 nmol/1;P = 0.02). These data demonstrate that in stimulated cyclesmany follicles, usually the smaller ones, fail to rupture, evenafter HCG administration. Complete LUF syndrome, despite a strongexogenous ovulatory signal, and the absence of any differencein peri-ovulatory hormonal parameters, indicates that the defectcausing LUF resides in the follicle itself and/or hormonal changesduring the follicular phase.