Efficacy of Folinic Acid in Comparison to Folic Acid for Reducing Side Effects of Methotrexate in Children with Juvenile Idiopathic Arthritis

Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.

Characterization of folic acid,5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters:impact on pregnancy and development

Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these processes on health also extend to cell proliferation,folate deficiency anemia,and reduction of the risk of birth defects during pregnancy.The primary objective of this study was to characterize the binding affinities of different folate forms,folic acid(FA),5-methyltetrahydrofolate(5MTHF),and folinic acid,to the folate receptorsαandβ,and to the bovine milk folate binding protein.These three dietary forms of folate are found in enriched grains(FA),various fruits and leafy vegetables(folinic acid),and red blood cells(5MTHF).Methods:The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.Results:Our results indicated that FA had the highest affinity for all folate receptors,followed by 5MTHF,and lastly,by folinic acid,examined by several orders of magnitudes.Conclusion:These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.

Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.

Folin-Ciocalteu法测定苹果醋饮料的总多酚含量

研究Folin-Ciocalteu法测定苹果醋饮料中总多酚含量的最适测定条件,并对该方法进行了分析评价。结果表明多酚含量的最佳测定条件为:样品用量1.0mL、福林-酚试剂2.5mL、12%碳酸钠溶液4.0mL、反应温度45℃、反应时间1.5h、测定波长756nm。吸光度与多酚含量在0～6μg/mL范围内呈良好的线性关系(y=0.1238x+0.0098,R2=0.9992),方法的加标回收率为101.2%,相对标准偏差为2.8%(n=5)。该方法精密度高、稳定性好,适用于苹果醋饮料中总多酚含量的测定。

核桃种皮中多酚的测定及种皮对核桃贮藏品质的影响

以核桃种皮为原料，没食子酸为对照品，建立核桃种皮中总酚测定的Folin—Ciocalteu比色法，并考察了贮藏过程中核桃种皮多酚对核桃仁品质的影响。研究表明，Folin—CiocalteuI：E色法测定核桃多酚含量的适宜条件为，样品提取液1mL，Folin—Ciocalteu试剂1．5mL，20％碳酸钠溶液lmL、反应温度60℃、反应时间60min、测定波长765nm，样品提取溶剂为60％乙醇，平均回收率99．86％（RSD2．87％）。没食子酸对照品在4．4—30．8μg／mL范围内吸光度与其质量浓度呈良好的线性关系，R2=0．9994。该法操作简单、精密度高、稳定性好、回收率高，可用于测定核桃种皮中多酚含量。用该法测定核桃不同部位多酚分布为：核桃种皮（21．73％）〉核桃青果皮（6．37％）〉核桃壳（2．92％）〉核桃仁（0．77％）。核桃贮藏过程中。种皮中总酚含量先增加后趋于平稳，酸价和过氧化值是一直增加的．说明种皮对核桃品质变化影响较小。

石榴叶总酚测定及提取工艺研究

以石榴叶为原料,采用Folin-Ciocalteu法定量测定石榴叶提取液中总酚含量,通过单因素试验和正交试验对石榴叶总酚的提取工艺进行探讨。确定其最佳提取条件为:料液比1:25(g/ml),温度70℃,提取溶剂为75%乙醇,提取时间1.5h。综合考虑成本因素,原料过1mm筛较为适宜,按照该工艺提取石榴叶总酚的得率为16.63%。

Folin-Ciocalteu法测定迷迭香中总酚酸含量

目的:建立Folin-Ciocalteu法测定迷选香总酚酸含量的方法。方法:以没食子酸为对照品研究了Folin-Ciocalteu法测定迷迭香中酚酸类物质含量的适宜条件。结果:适宜的比色条件为Folin-Ciocalteu试剂与10% Na2CO3体积比为1∶3,Folin-Ciocalteu试剂1.5mL,显色温度25℃,反应时间2h,检测波长765nm。浓度为5～50μg/mL时与其吸光值呈良好的线性关系,测定方法的平均回收率为101.2%。结论:该法有较好的准确度和重现性。

不同菱角壳提取物抑制肺癌A549细胞生长的研究

目的研究不同菱壳水和乙醇提取物的抗癌活性。方法采用Folin比色法测定不同品种菱壳提取物中多酚的含量,通过MTT法测定二角菱壳、四角菱壳的水提取物、醇提取物对肺癌A549细胞生长抑制作用。结果四角菱壳多酚含量高于二角菱壳,醇提物多酚含量高于水提物;二角菱壳醇提取物对肺癌A549细胞的抑制率高于水提物,差异具有统计学意义(P<0.01);四角菱壳水提物对抑制率高于二角菱壳水提物肺癌A549细胞的生长,差异具有统计学意义(P<0.01)。结论菱角壳提取物对肺癌A549细胞生长具有较强的抑制作用,且菱角壳的醇提取物优于水提取物,四菱角壳优于二角菱壳。

分光光度法测定仙鹤草总酚含量的方法研究

目的建立测定仙鹤草中总酚含量的测定方法。方法通过可见分光光度法,以没食子酸为标准品,采用Folin-Ciocalteus试剂,在装有仙鹤草样品的10mL容量瓶中,依次加入Folin-Ciocalteus试剂0.5mL,20%Na2CO31.7mL,在室温条件下放置90min,然后在波长760nm和660nm测定吸光度。结果总多酚浓度在0～10.4 mg/L与吸光度有良好的线性关系。760nm时的回归方程为y=0.091.8x+0.012.9,R2=0.999 3,加标回收率为98.4%～99.8%;660nm时的回归方程为y=0.084 7x-0.002 6,R2=0.999 7,加标回收率为101.2%～101.9%。结论在760nm和660nm 2个波长处测定的结果,都具有良好的精密度、重复性和回收率,可以作为测定仙鹤草多酚定量分析的参考方法。

Folin B分光光度法测定蔬菜中维生素C的含量

提出了一种测定维生素C的新方法,它是基于Folin B 试剂与抗坏血酸在pH=3的三氯乙酸酸性介质中反应生成脱氢抗坏血酸,反应产物在910nm波长处有最大吸光度进行定量分析。该方法的线性范围为(0-50.0μg/mL,相关系数r=0.99986,回收率为98.12%-102.15%。

Folin-Denis分光光度法测定五倍子中单宁酸的含量

[目的]探索Folin-Denis可见分光光度法精确快速测定五倍子中单宁酸含量的可行性。[方法]用水温浸提法消化五倍子后，其提取液中的单宁酸与Folin-Denis试剂反应形成稳定的蓝色配合物，通过测定该反应体系的吸光度来确定单宁酸的含量，同时验证最佳的检测条件。[结果]单宁酸浓度在0．002-0．010mg／ml范围内，吸光度和单宁酸浓度具有良好的线性关系，符合回归方程A=44．31c＋0．008，R。=O．999O，加标回收率为97．8％～101．8％，相对标准偏差（RSD）〈0．5％，单宁酸平均含量为82．O％。[结论]利用Folin-Denis分光光度法测定五倍子中单宁酸的含量，操作简便、快速、精密度高、重现性好、加标回收率较高。

鲜竹沥质量标准的初步研究

用Folin酚试剂测定鲜竹沥中酚类和水扬酸类成分的总含量,作为鲜竹沥原汁和市售产品质量的主要指标。

Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer

AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.

Folin-Ciocalteu比色分光光度法测定鲜笋中的单宁

实验采用Folin-Ciocalteu比色分光光度法测定新鲜竹笋中单宁的含量。结果显示:新鲜竹笋待测液加入Folin-Ciocalteu显色剂2 mL,9%的Na2CO3溶液5 mL,定容混匀后于40℃静置60 min,并在770 nm处测定其光密度值(OD值),经计算得到新鲜毛竹冬笋和毛竹春笋单宁质量分数分别为0.131 4%、0.330 5%。以单宁为标样,单宁量在0.000～0.020 mg/mL范围之内服从比耳定律,回归方程y=98.957x+0.029,相关系数R2=0.992 7,据此线性回归方程定量测定鲜笋中的单宁,该方法具有方便、操作简单、精密度高、稳定性好及准确可靠等优点。

长白山笃斯越桔叶片中多酚类化合物提取技术研究

本实验采用Folin试剂分光光度法来测定笃斯越桔叶片中多酚类化合物含量,获得线性关系良好的多酚类化合物标准工作曲线:y=0.0228x-0.0021(R2=0.9994),并通过对比分析、正交试验设计等试验方法优化出乙醇浸提法提取笃斯越桔多酚类化合物的最佳工艺参数:提取时间为60min,乙醇浓度为60%,料液比为1:100。

生姜中姜辣素含量的测定

Folin酚试剂与姜辣素中的酚基可发生蓝色显色反应。以香草醛为标准样品,用均匀设计法安排实验,考察了Folin酚法测定姜辣素含量的实验中各实验条件对显色反应的影响。以工作曲线的线性相关系数R作为判据,在680nm的条件下进行光度测量,得到了最优条件,在此条件下制作的工作曲线线性相关系数为0.99989。用此工作曲线测定姜辣素的含量,所得结果重现性良好。该法操作简便,准确度高,可用于产品定量检测。

Folin比色法测定鹿衔草提取物中总多酚的含量

目的:建立Folin比色法测定鹿衔草提取物中总多酚的含量。方法:采用分光光度法测定。以没食子酸为指标,检测波长730 nm。结果:没食子酸在1.08μg/mL^6.48μg/mL范围内线性良好,相关系数为0.9999,加样回收率99.7%,RSD为1.2%(n=9)。结论:本法测定鹿衔草提取物中总多酚的含量,结果准确可行。

苹果渣中苹果多酚的提取工艺优化

采用有机溶剂提取法从苹果渣中提取苹果多酚,研究了提取溶剂乙醇体积分数、料液比、提取温度、提取时间对苹果多酚提取量的影响。通过单因素实验及正交实验确定苹果多酚的最佳提取工艺条件为:提取溶剂乙醇体积分数70%、料液比1∶25(g∶mL)、提取温度30℃、提取时间40min,此条件下苹果多酚的提取量为2.982mg.g-1。

水芹总酚酸胶囊质量控制方法的研究

目的初步建立水芹总酚酸胶囊的质量控制标准。方法采用薄层色谱法对水芹总酚酸进行定性鉴别;采用Folin酚法测定水芹总酚酸含量;采用高效液相色谱法测定总酚酸中绿原酸含量,色谱条件:DiamonsilC18柱,流动相:A:乙腈-甲醇(10∶1);B:0.4%磷酸,梯度洗脱;检测波长:325nm;流速:1ml/min;柱温:25℃。结果按现有生产工艺,水芹总酚酸胶囊总酚酸含量最高为32.42%,绿原酸最高为9.3%。结论 Folin酚法和高效液相色谱法能精确测定水芹总酚酸胶囊中总酚酸和绿原酸含量,可作为水芹总酚酸胶囊的质量控制方法 。

降解铬革屑微生物发酵条件的优化研究

对一株能粗降解铬革屑菌株的发酵条件进行优化,通过Folin试剂法测定了不同发酵条件下发酵液的蛋白酶活性,确定了菌株W_(1-1)的最适产酶条件。研究表明:菌株的最适产酶条件为葡萄糖9.0%,酵母膏0.5%,CaCl_20.3%,K_2HPO_40.3%,MgSO_4 0.2%,初始pH 8.5,装液量90mL(90/250mL三角瓶),接种量4.0%,种龄14h,发酵温度37℃,发酵时间36h。在此条件下,测得发酵液的蛋白酶活力为37.36u/mL,比优化前的产酶量提高了35.4%;最后,采用该菌株在最适产酶条件下对铬革屑进行降解,降解率达到71.38%。