High radiochemical yield synthesis of 3'-deoxy-3'-[18F]fluorothymidine using (5'-O-dimethoxytrityl-2'-deoxy-3'-O-nosyl-beta-D-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor

We prepared 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) from 3'-O-nosyl thymidine derivative 3 or its pyrimidine ring N-BOC-protected analogue 5 and optimized [(18)F]fluorination condition for a high radiochemical yield. The optimal condition for [(18)F]fluorination with precursor 3 was 30 mg (41.1 micromol)/300 microl CH(3)CN at 130 degrees C for 5 min, while precursor 5 required 34 mg (40 micromol)/300 microl CH(3)CN at 110 degrees C for 5 min. After HPLC purification at neutral pH, we achieved high radiochemical yields of 40 +/- 5.2% and 42 +/- 5.4% (decay-corrected) within 60 min of preparation time with radiochemical purities of >97%.     

Effect of lifetime lactation on breast cancer risk: a Korean women's cohort study

The objective of our study was to examine the effect of lifetime lactation on breast cancer risk among premenopausal women. The data were from a prospective cohort study with a follow-up period of 6 years in Korea (1995-2000). The cohort was composed of 110,604 premenopausal parous Korean women, aged 20 years and older, who received health insurance from the Korea Medical Insurance Corporation and who had medical evaluations in 1992 and 1994. Multivariate Cox proportional hazard models were tested, controlling for age, age at menarche, number of children, age at first pregnancy, oral contraceptive use, smoking, exercise and obesity. At baseline, 57,440 (51.9%) reported breastfeeding and 4,584 (4.1%) reported breastfeeding more than 24 months. From 1995-2000, 360 incident cases of breast cancer (61.8/100,000 person-years) occurred. Compared to parous women who had no history of lactation, a period of lactation of 13-24 months decreased the risk of breast cancer (RR, 0.7; 95% CI, 0.5-1.1), and this risk was decreased even further for those who breastfed for more than 24 months (RR, 0.6; 95% CI, 0.3-1.0). There was a clear trend of decreasing breast cancer risk with the duration of lactation (p for trend <0.001). In conclusion, our study of a large Korean cohort provides additional empirical evidence to current theoretical conjecture that lactation decreases the risk of breast cancer among premenopausal women.     

Genistein抑制人卵巢癌细胞系SKOV3增殖和诱导凋亡发生的研究

背景与目的:许多研究表明 Genistein对多种肿瘤细胞有抑制作用,但有关 Genistein对卵巢癌细胞作用的报道很少.本研究旨在通过观测 Genistein对人卵巢癌细胞系 SKOV3的抑制增殖和诱导凋亡作用,探讨其抗癌作用的机理.方法:应用四甲基偶氮唑盐( MTT)法检测不同浓度 Genistein对 SKOV3的生长抑制作用;吖啶橙 /溴乙锭( AO/EB)荧光染色法及电镜观察凋亡细胞及凋亡小体;流式细胞仪分析细胞周期及凋亡率;琼脂糖凝胶电泳检测凋亡特征性 DNA梯形带;免疫细胞化学法及 RT- PCR法分别检测细胞增殖凋亡调控相关蛋白及其 mRNA的表达。结果： Genistein对 SKOV3细胞的增殖抑制作用呈时间及浓度依赖性, 20 μ mol/L和 40 μ mol/L Genistein作用 72 h后,细胞的生长抑制率达 72. 07％和 74. 93％。 20 μ mol/L Genistein作用 SKOV3细胞 48 h后出现细胞周期的 G2/M期阻滞。荧光显微镜和电镜均观察到用药后凋亡细胞典型的形态学特征。细胞凋亡率以 Genistein 20 μ mol/L组最高,达 23. 7％。凝胶电泳观察到特征性 DNA梯形带。 20 μ mol/L Genistein作用 SKOV3 48 h后, bcl- 2基因表达水平降低,而 p21WAF1/CIP1和 bax基因表达增加（ P< 0. 05）; PCNA、Bcl- 2及 cyclin B1蛋白表达水平降低, Bax、p21WAF1/CIP1蛋白表达增加（ P< 0. 01）。结论： Genistein可抑制卵巢癌细胞系 SKOV3的增殖并诱导其发生凋亡, Genistein可能通过上调 p21WAF1/CIP1基因及蛋白水平、下调 cyclin B1及 PCNA蛋白表达水平抑制增殖;通过下调 bcl- 2基因及蛋白表达、上调 bax基因及蛋白表达诱导卵巢癌细胞凋亡.     

Hypothermia reduces sulphur mustard toxicity

The effect of temperature on the development of sulphur mustard (HD)-induced toxicity was investigated in first passage cultures of human skin keratinocytes and on hairless guinea pig skin. When cells exposed to HD were incubated at 37 degrees C, a concentration-dependent decline in viability was observed that was maximal by 2 days. In contrast, no significant HD-induced toxicity was evident up to 4 days posttreatment when the cells were incubated at 25 degrees C. However, these protective effects were lost by 24 h when the cells were switched back to 37 degrees C. The protective effects of hypothermia were also demonstrated when apoptotic endpoints were examined. The HD concentration-dependent induction of fragmented DNA (as quantitated using soluble DNA and the TUNEL reaction), morphology, and p53 expression were all significantly depressed when cell cultures were incubated at 25 degrees C compared to 37 degrees C. When animals were exposed to HD vapour for 2, 4, and 6 min and left at room temperature, lesions were produced whose severity was dependent on exposure time and that were maximal by 72 h posttreatment. Moderate cooling (5-10 degrees C) of HD exposure sites posttreatment (4-6 h) significantly reduced the severity of the resultant lesions. However, in contrast to the in vitro results, these effects were permanent. It appears that the early and noninvasive act of cooling HD-exposed skin may provide a facile means of reducing the severity of HD-induced cutaneous lesions.     

Neutralization of proANP (1-30) exacerbates hypertension in the spontaneously hypertensive rat

1. The aim of the present studies was to determine the role of proANP (1-30) in the regulation of arterial pressure. It was hypothesized that blocking endogenous proANP (1-30) would exacerbate the hypertension in susceptible animal models. 2. Pentobarbital-anaesthetized spontaneously hypertensive rats (SHR) were pretreated i.v. with 1.2 mL rabbit serum containing an antibody directed specifically against rat proANP (1-30) (SHR-AB group; n = 7) or an equal volume of normal rabbit serum as a control (SHR-NRS group; n = 5). 3. Following a 1 h equilibration period and two 30 min baseline periods, rats were volume expanded with 3 mL of 6% albumin in Krebs' solution and observed for an additional 3 h to determine the effects of the anti-proANP on arterial pressure. 4. Arterial pressure increased in both groups compared with their own baselines with volume expansion, but was significantly greater in the anti-proANP SHR group compared with the SHR-NRS group throughout the volume expansion period. A maximum difference of 21 mmHg between the anti-proANP SHR group and the NRS-SHR group was observed at 150 min of the study (183 +/- 5 vs 162 +/- 3 mmHg, respectively; P < 0.005. 5. These results suggest a protective role for proANP (1-30) in the SHR model of hypertension.     

Meconium concentration and amniotic fluid index influence the outcome of amnioinfusion

BACKGROUND: To determine the usefulness of amnioinfusion as a function of meconium concentration and amniotic fluid index. METHODS: This was a prospective study of 206 pregnant women in whom amniotic fluid was moderately or heavily stained with meconium, according to subjective evaluation. The women were assigned randomly to receive amnioinfusion (n=103) or no amnioinfusion (control group, n=103). The results were compared in women with =/<15 % or >15 % meconium in the amniotic fluid (measured by centrifugation), and in women in whom the amniotic fluid index calculated 60 min after insertion of the amnioinfusion catheter was <10 or =/>10. RESULTS: In women with >15% meconium, amnioinfusion decreased the rate of cesarian sections motivated by fetal distress (2.5% vs 22.2%), and in women with =/<15% meconium, amnioinfusion decreased the presence of meconium below the vocal cords (6.4% vs 25.9%). Greater benefits after amnioinfusion were seen in women with an amniotic fluid index =/>10: the rate of cesarian sections was lower (1.3% vs 13.3%), as was the frequency of meconium below the vocal cords (10.1% vs 33.3%). CONCLUSIONS: Beneficial effects of amnioinfusion were seen in women with high and low concentrations of meconium, and with high and low amniotic fluid indexes. These criteria should therefore not be used to decide whether amnioinfusion is indicated when the amniotic fluid is moderately or heavily stained with meconium.