补充叶酸对结、直肠癌发生的双面影响

叶酸在DNA的合成和复制中起着重要作用,原有研究提示补充叶酸可以降低罹患结、直肠癌的风险,但近年来的研究对此提出了异议。本文通过相关文献复习发现,补充叶酸虽可在人体未形成结、直肠癌之前通过提高DNA甲基化的稳定性而产生预防肿瘤的作用,但当肠道内已形成肿瘤微小病灶后,补充叶酸反能产生促进肿瘤生长的作用,这可能与叶酸会促进肿瘤细胞的增殖有关。此外,补充叶酸对预防结、直肠癌的有效性有时间和剂量依赖性。因此,在应用叶酸预防结、直肠癌前应常规使用结肠镜进行肿瘤筛查,以排除早期微小腺瘤。有条件的还应进行红细胞及乙状结肠上皮内的叶酸浓度测定,以评估患者的叶酸水平并据此避免补充的叶酸剂量过大。叶酸水平与罹患结、直肠癌的关系仍有待学者们更深入研究的揭示。     

Bisphosphonate use and risk of colorectal cancer: a systematic review and meta-analysis

Aim

A growing body of evidence suggests that bisphosphonates may have chemopreventive potential against colorectal cancer. Our aim was to examine this association through a meta-analysis of observational studies.

Methods

A comprehensive search for relevant articles published up to October 2012 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects and the fixed effects models. Subgroup and sensitivity analyses were also performed.

Results

Eight large population-based epidemiological studies (one case-control, two nested case-control analyses within a cohort and five cohort studies), involving more than 630 000 participants, contributed to the analysis. We found no evidence of publication bias. However, significant heterogeneity was detected among the cohort studies. The analysis revealed a significant protective association between bisphosphonate use and colorectal cancer risk (fixed RR = 0.85, 95% CI 0.80, 0.90, random RR = 0.85, 95% CI 0.75, 0.96). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis confirmed the stability of our results. Furthermore, we found evidence for a dose effect; Long term bisphosphonate use was associated with a 27% decrease in the risk of developing colorectal cancer as compared with non-use (RR = 0.73, 95% CI 0.57, 0.93).

Conclusion

Our findings support a protective effect of bisphosphonates against colorectal cancer. However, further evidence is warranted.     

Exposure to bisphosphonates and risk of colorectal cancer

Animal and in vitro studies suggest that the use of bisphosphonates (BPs) may be associated with reduced risk for colorectal cancer (CRC). However, results from these studies have been inconsistent. The aim of our study was to review and summarize the evidence provided by longitudinal studies on the association between BP use and CRC risk A comprehensive literature search for articles published up to October 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risks (RRs) or odds ratios were calculated. Six reports (four case–control studies and two cohort studies) published between 2010 and 2012 were identified. There was evidence of an association between any use of BPs and CRC risk using a fixed-effects model (RR = 0.80, 95% confidence interval = 0.74, 0.85) and a random-effects model (RR = 0.80, 95% confidence interval = 0.71, 0.90). However, we did not observe any evidence of a trend with increasing duration of use. Our findings indicate that there is evidence of an association between any use of BP and reduced CRC risk. However, this subject deserves further investigation.     

叶酸水分测定方法的研究

目的: 对叶酸的水分测定方法进行研究。方法:采用热重分析法(TG)、差示扫描量热法(DSC)等方法对叶酸的热力学行为进行研究,并建立了一个新的卡式炉-卡尔费休法测定水分的方法。结果: 采用新建立的方法测定国内及美国药典会(USP)叶酸对照品水分,结果分别为8.13%与8.00%,标准偏差分别为0.74%与0.28%(n=3)。结论: 本文建立的卡式炉-卡尔费休法方法简单方便,准确可靠,适合批量样品的测定,为叶酸对照品的标定及其原料的质量控制提供依据。     

Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability

Previous in vitro studies using Caco-2 cell monolayers suggested a possible interaction between green and black tea and folic acid at the level of intestinal absorption. The main purpose of the present study was to investigate a possible pharmacokinetic interaction between tea and folic acid in healthy volunteers. In an open-labeled randomized cross-over study, the pharmacokinetic interaction between tea and folic acid (0.4 mg and 5 mg) was investigated in healthy volunteers. Water was used as the reference drink. Subjects ingested 0.4 mg folic acid tablets with water, green or black tea (0.3 g extract/250 ml) or 5 mg folic acid tablets with water or green tea (0.3 g extract/250 ml). Blood samples were collected over a period of 8 h. Serum folate analysis was carried out by a competitive immunoassay which uses direct chemiluminescent technology. At the 0.4 mg folic acid dose, green and black tea reduced the mean C(max) of serum folate by 39.2% and 38.6%, and the mean AUC(0 --> infinity) by 26.6% and 17.9%, respectively. At the 5 mg folic acid dose, the mean C(max) of serum folate was reduced by 27.4% and the mean AUC(0 --> infinity) was decreased significantly by 39.9% by the co-application of green tea. The present results suggest an in vivo interaction between tea and folic acid with even low concentrations of green and black tea extracts yielding decreased bioavailabilities of folic acid. Copyright (c) 2008 John Wiley & Sons, Ltd.