颈动脉注入卡氮芥与注入卡氮芥＋卡铂治疗恶性胶质瘤的对比观察

为对比观察颈动脉注入卡氮芥与注入卡氮芥 卡铂治疗大脑恶性胶质瘤的效果，对40例恶性胶质瘤随机分成两组各20例。肿瘤术后采用颈动脉注入罂粟碱开放血脑屏障，再分别注入卡氮芥和注入卡氮芥 卡铂，并进行10年的随访观察。结果表明，卡氮芥组(Ⅰ组)中位生存期23．33个月；卡氮芥 卡铂组(Ⅱ组)中位生存期29．4个月；两组差异无显著意义(P=O．25)。Ⅱ组注药眼部症状较Ⅰ组轻。结论：颈动脉注入卡氮芥 卡铂与注入卡氮芥治疗恶性胶质瘤的效果基本一致，但病人的痛苦较颈动脉注入卡氮芥少。     

顺铂及其类似物

一、前言目前,临床用于治疗各种肿瘤的化疗剂中效果最好的药物之一顺铂(cusplatin,顺-二氯二氨合铂(Ⅱ),图1)是唯一的金属配合物(卡波铂也已上市——译注)。     

铂类抗肿瘤配合物的研究进展

铂类药物因抗癌谱广、疗效显著而在临床中被广泛使用。自1978年顺铂应用于临床以来,卡铂、奥沙利铂相继被美国FDA批准,乐铂、奈达铂和依铂分别在中国、日本以及韩国上市。然而,铂类药物的毒副作用和耐药性大大限制了其应用和开发。为提高铂类药物的疗效以及克服其缺陷,大量的新型铂类配合物被设计合成,并在不同阶段开展疗效试验。除与顺铂类似的铂(Ⅱ)配合物之外,近年来作为前药的铂(Ⅳ)配合物也被广泛研究。从铂(Ⅱ)配合物和铂(Ⅳ)配合物2个方面,总结近年来铂类抗肿瘤配合物取得的研究进展,并对配体的选择与配合物设计、作用机制、抗肿瘤效果以及临床应用前景进行概述,以期对今后的新药开发和临床应用有所裨益。     

复方苦参注射液联合白介素-Ⅱ、顺铂治疗恶性胸腔积液的近期疗效观察

目的观察复方苦参注射液联合白介素-Ⅱ、顺铂治疗恶性胸腔积液的近期疗效和毒副作用。方法将153例恶性胸腔积液患者随机分为试验组(复方苦参、白介素-Ⅱ、顺铂胸腔内注射联合复方苦参静点)与对照组(白介素-Ⅱ、顺铂胸腔内注射);对比分析患者近期治疗效果、生活质量(QOL)、毒副反应等方面变化。结果试验组近期治疗效果优于对照组,差异有统计学意义(P<0.05)。试验组较对照组生活质量有明显改善,毒副作用明显降低,差异均有统计学意义(P<0.05)。结论复方苦参注射液联合白介素-Ⅱ、顺铂治疗恶性胸腔积液可明显提高近期疗效,改善患者生活质量,降低毒副作用。     

碳铂和顺铂毒性的比较

<正> 1969年Roseuberg等发现铂类化合物有抗肿瘤活性,1972年,国家癌症研究所(NCI)推荐顺铂(cis-diammine dich-loroplatinum Ⅱ)进行临床试验,结果证实该药对多种癌症均有显著疗效,但肾脏、耳、胃肠道等毒性较大,近年来合成了一系列新的铂类化合物,其中碳铂(car-boplatin)疗效与顺铂相仿,而毒性(尤     

草酸铂经区域性动脉灌注化疗治疗晚期胰腺癌21例分析

目的 观察草酸铂(奥沙利铂)用于区域性动脉灌注化疗治疗晚期胰腺癌的临床疗效。方法 采用Seldinger法将导管插至腹腔动脉、肠系膜上动脉，再插至肿瘤供血动脉(如胃十二指肠动脉、胰背动脉或胰十二指肠下动脉)依次灌注5-Fu 1000mg和奥沙利铂200mg。结果 21例患者中，完全缓解(CR)2例，部分缓解(PR)4例，无变化(NC)10例，进展(PI))5例；毒副反应均为I～Ⅱ度，治疗中未出现肾功能的损害。结论 奥沙利铂动脉灌注是安全的，并且在晚期胰腺癌区域性动脉灌注化疗中有较好的疗效。     

汞配合物的合成及表征

顺氯氨铂(cis-platin,CD-DP)抗肿瘤活性的发现,为金属配合物在药学方面的应用开辟了崭新的研究领域。本文仿照1,1-环丁烷二羧酸二氨合铂的合成方法展开了一系列的实验研究,合成了三个新的汞(Ⅱ)的配合物:丙二酸一氨合汞(Ⅱ)、1,1环丁烷二羧酸一氨合汞(Ⅱ)和1,1-环戊烷二羧酸一氨合汞(Ⅱ),并对其进行了表征。     

紫杉醇联合卡铂治疗非小细胞肺癌61例近期疗效观察

目的 探讨紫杉醇(Taxol)联合卡铂(CBP)治疗非小细胞肺癌(NSCLC)近期疗效和毒副反应。方法 紫杉醇135mg／m。静滴每周期第1天使用，用紫杉醇前进行预处理，卡铂350mg／m^2，第1天使用，3周为1周期，每个病例完成2～3周期。结果 61例疗效部分缓解(PR)26例，总有效率为42．6％，初治者总有效率为43．6％，复治者总有效率为40．9％。毒副反应主要表现为一度以下白血球下降和Ⅰ～Ⅱ度消化遒反应。结论 紫杉醇是一种新的抗肿瘤细胞微管结构的药物，它与卡铂组成的TC方案治疗非小细胞肺癌近期疗效比CAP方案(环磷酰胺 阿霉素 顺铂)、EP方案(足叶乙甙 顺铂)和VP方案(长春酰胺 顺铂)为好，毒性小，是目前治疗NSCLC较理想的方案。     

联合给药能有效对抗大鼠腹腔播散性癌

本文评价了使用顺铂、解毒药硫代硫酸钠(STS)和血管紧张素Ⅱ(AT-Ⅱ)治疗大鼠腹腔播散性癌的疗效。雌性WKA 大鼠于腹腔接种10~6活的RBT-Ⅰ细胞后的第4或第7天接受治疗。iv AT-Ⅱ(16.5μg/kg,浓度为1μg/ml),共持续11min;当开始iv AT-Ⅱ1min 后,快速ip 15mg/kg 顺铂(3ml/200g体重);iv AT-Ⅱ结束后立即iv 1580mg/kgSTS(与顺铂的克分子比为1:200),iv 持续5min,该方法称之为改良的联合给药方案     

第二代抗肿瘤铂化合物血浆结合的体外研究

对顺氯氨铂的五种类似物与离体血浆中分子量>50,000d 的成分(下简称PF)的结合动力学进行了研究。这五种药物包插,一个Pt(Ⅳ)绍合物:顺-二氯-反-二羟-双(异丙胺)铂(JM_9);四个Pt(Ⅱ)络合物:羟丙二:酸脂二氨铂(JM_5)、1,1-环丁二酸脂二氨铂(JM_8)、丙二酸脂-1,2-环己二胺铂(JM_(74_)及水合硫酸脂(1,2-环己二胺)铂(JM_(20))。     

Metabolism of steroids by cytochrome P450 2C9 variants

CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild‐type CYP2C9 and ten mutants were co‐expressed with NADPH‐cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward steroids were examined. CYP2C9.2, CYP2C9.3, CYP2C9.4, CYP2C9.16, CYP2C9.28, CYP2C9.48 and CYP2C9.52 had higher testosterone 6β‐hydroxylation than CYP2C9.1. CYP2C9.4 showed higher progesterone 6β‐hydroxylation activity than CYP2C9.1. CYP2C9.28 and CYP2C9.48 showed higher progesterone 11α‐hydroxylation activity than CYP2C9.1. CYP2C9.48 showed higher progesterone 16α‐hydroxylation activity than CYP2C9.1. CYP2C9.2, CYP2C9.3, CYP2C9.16 and CYP2C9.30 had higher estrone 16α‐hydroxylation activity than CYP2C9.1. CYP2C9.3 had higher estrone 11α‐hydroxylation activity than CYP2C9.1. CYP2C9.39 and CYP2C9.57 showed similar activities to CYP2C9.1. These results indicate that the substrate specificity of CYP2C9.39 and CYP2C9.57 was not changed, but CYP2C9.2, CYP2C9.3, CYP2C9.4, CYP2C9.16, CYP2C9.28, CYP2C9.30, CYP2C9.48 and CYP2C9.52 showed different hydroxylation activities toward steroids compared with CYP2C9.1.     

卵巢甲状腺类癌临床病理探讨

目的探讨卵巢甲状腺类癌的临床病理特征、诊断及鉴别诊断。方法对2例发生在卵巢甲状腺类癌病例应用免疫组化Syn,CgA,S-100,CT,Vimtime,Tg,CK,NSE,P63,Ki67,CEA,α—inhibin进行检测,并结合相关文献进行讨论。结果2例患者均为绝经后女性,例1患者以盆腔包块为主要表现,伴有便秘,血CA199升高,例2患者因手术切除其他肿瘤及附件,送病理活检发现。2例患者巨检肿瘤均为单纯型。镜检肿瘤均由甲状腺组织及类癌组织构成,类癌为梁状与岛状混合型。免疫组化：2例患者类癌细胞Syn（2／2＋）,CgA（2／2＋）,NSE（1／2＋）,Ki67（3％＋,5％＋）,CK（I／2＋）,S-100（2／2-）,CEA（2／2-）,P63（2／2-）,CT（2／2-）,Vimtime（2／2-）,Tg（2／2-）,α-inhibin（2／2-l甲状腺滤泡Tg（2／2＋）,CK（2／2＋）,Vimtime（1／2＋）,Syn（2／2-）,CgA（212-）,NSE（2／2-）,Ki67（2／2-）。S-100（2／2-）,CEA（2／2-）,P63（2／2-）,CT（2／2-）,α-inhibin（2／2～）。2例患者均为I期,例1患者术后行化疗,例2术后未做任何治疗,分别随访57个月及2个月,均未见复发及转移。结论卵巢甲状腺类癌是-种非常罕见的具有独特临床病理学特征的高度特殊性生殖细胞肿瘤,伴有甲状腺组织分化,一般预后良好,要与小圆形细胞肿瘤鉴别,结合免疫组化,可与之鉴别。     

河南省小麦、玉米及蔬菜优质高产高效平衡施肥

介绍农作物高产优质施肥技术的田间试验研究情况。田间试验结果表明:小麦在氮磷肥配施时(N270kg/hm2、P2O5120kg/hm2),K2O最佳用量为180kg/hm2,小麦最高产量达6880kg/hm2;玉米在氮磷肥配施时(N225kg/hm2、P2O5120kg/hm2),K2O最佳用量为180kg/hm2,玉米最高产量达7640kg/hm2;萝卜在氮磷肥配施时(N300kg/hm2、P2O5225kg/hm2),K2O最佳用量为300kg/hm2,萝卜最高产量达79860kg/hm2;白菜在氮磷肥配施时(N300kg/hm2、P2O5225kg/hm2),K2O最佳用量为300kg/hm2,白菜最高产量达95050kg/hm2。     

Effect of hydrogen peroxide on Ca2+ mobilisation in human platelets through sulphydryl oxidation dependent and independent mechanisms

Using Fura-2-loaded human platelets we studied the nature of the mechanisms involved in Ca2+ signalling mediated by H2O2. In a Ca2+-free medium, H2O2 (10 microM-100 mM) induced a concentration-dependent increase in [Ca2+]i. Depletion of either agonist-sensitive or mitochondrial Ca2+ pools reduced this effect while depletion of both stores abolished it. Xestospongin C, an inositol 1,3,5-trisphosphate (IP3) receptor inhibitor, reduced Ca2+ release evoked by 1 mM H2O2 by 45%, indicating that H2O2-induced Ca2+ release involves interaction with IP3 receptors. Blockade of the IP3 turnover by lithium or treatment with U-73122 did not modify H2O2-induced Ca2+ release from the agonist-sensitive pool, suggesting the involvement of a mechanism independent of IP3 generation. H2O2 inhibited Ca2+ reuptake into the agonist-sensitive stores mediated by the sarcoendoplasmic reticulum Ca2+ ATPase (SERCA). Thimerosal (5 microM), a sulphydryl reagent, induced Ca2+ release from the agonist-sensitive stores. This event was impaired by treatment with 2 mM DTT, which also inhibited H2O2-induced Ca2+ release from the agonist-sensitive pool but not from mitochondria. H2O2 reduced the ability of the plasma membrane Ca2+ ATPase (PMCA) to extrude Ca2+ by 75%, an effect that was unaffected by DTT. Consistent with this, thimerosal did not modify the PMCA activity. Finally, exposure to H2O2 triggered platelet aggregation, which was slower than that observed after agonist stimulation. We conclude that H2O2 induced Ca2+ release from agonist-sensitive stores by oxidation of sulphydryl groups in SERCA and the IP3 receptors independently of IP3 generation. In addition, H2O2 induced Ca2+ release from mitochondria and inhibited the PMCA activity by different mechanisms in human platelets.     

Metabolism of 7‐ethoxycoumarin,safrole, flavanone and hydroxyflavanone by cytochrome P450 2A6 variants

CYP 2A6 is a human enzyme that metabolizes many xenobiotics including coumarin, indole, nicotine and carcinogenic nitrosamines. The gene for CYP2A6 is polymorphic. There are few data available to clarify the relationship between P450 genetic variants and the metabolism of materials in food. The CYP 2A6 wild‐type protein and 13 mutants (CYP2A6.1, CYP2A6.2, CYP2A6.5, CYP2A6.6, CYP2A6.7, CYP2A6.8, CYP2A6.11, CYP2A6.15, CYP2A6.16, CYP2A6.17, CYP2A6.18, CYP2A6.21, CYP2A6.23 and CYP2A6.25) were co‐expressed with NADPH‐cytochrome P450 reductase in E. coli. The hydroxylase activities toward 7‐ethoxycoumarin, coumarin, safrole, flavanone and hydroxyflavanone were examined. Ten types of CYP2A6 variants except for CYP2A6.2, CYP2A6.5 and CYP2A6.6 showed Soret peaks (450 nm) typical of P450 in the reduced CO‐difference spectra and had 7‐ethoxycoumarin O‐deethylase activities. CYP2A6.15 and CYP2A6.18 showed higher activities for safrole 1′‐hydroxylation than CYP2A6.1. CYP2A6.25 and CYP2A6.7 had lower safrole 1′‐hydroxylase activities. CYP2A6.7 had lower flavanone 6‐ and 2′‐hydroxylase activities, whereas CYP2A6.25 had higher 6‐hydroxylase activity and lower 2′‐hydroxylase activity. Hydroxyflavanone was metabolized by CYP2A6.25, but was not metabolized by wild‐type CYP2A6.1. These results indicate that CYP2A6.25 possessed new substrate specificity toward flavonoids. Copyright © 2012 John Wiley & Sons, Ltd.     

H_2O_2预处理对NF-κB的激活作用特征及其细胞保护作用

目的探讨H2O2预处理对核转录因子-κB(NF-κB)的激活作用,并观察NF-κB在H2O2预处理诱导的适应性细胞保护中的作用。方法在PC12细胞建立H2O2预处理对抗高浓度H2O2诱导细胞凋亡的实验模型,分组如下:(1)空白对照组;(2)预处理组;(3)损伤组;(4)预处理+损伤组;(5)TPCK+预处理+损伤组;(6)TPCK组。应用碘化丙啶(PI)染色流式细胞术检测细胞凋亡率,甲氮甲唑蓝(MTT)法检测细胞存活率,免疫印迹法(Westernblot)测定NF-κB的表达水平,电泳迁移实验(EMSA)检测NF-κBDNA结合活性。结果H2O2预处理PC12细胞上调NF-κBp65的表达,增强DNA结合活性,并能明显地增加高浓度H2O2引起的NF-κBp65的表达(与损伤组比较,P<0.01)。H2O2预处理能使PC12细胞对抗高浓度H2O2引起的损伤,提高细胞存活率,降低细胞凋亡率(与损伤组比较,P<0.01)。NF-κB抑制剂甲苯磺酰苯丙氨酰氯甲酮(TPCK)可拮抗H2O2预处理对NF-κBp65的激活作用,并减弱H2O2预处理诱导的适应性细胞保护作用(与预处理+损伤组比较,P<0.01)。结论H2O2预处理对NF-κB的激活作用可能是其引起的适应性细胞保护机制之一。     

Structure activity and molecular modeling analyses of ribose- and base-modified uridine 5'-triphosphate analogues at the human P2Y2 and P2Y4 receptors

With the long-term goal of developing receptor subtype-selective high affinity agonists for the uracil nucleotide-activated P2Y receptors we have carried out a series of structure activity and molecular modeling studies of the human P2Y2 and P2Y4 receptors. UTP analogues with substitutions in the 2'-position of the ribose moiety retained capacity to activate both P2Y2 and P2Y4 receptors. Certain of these analogues were equieffective for activation of both receptors whereas 2'-amino-2'-deoxy-UTP exhibited higher potency for the P2Y2 receptor and 2'-azido-UTP exhibited higher potency for the P2Y4 receptor. 4-Thio substitution of the uracil base resulted in a UTP analogue with increased potency relative to UTP for activation of both the P2Y2 and P2Y4 receptors. In contrast, 2-thio substitution and halo- or alkyl substitution in the 5-position of the uracil base resulted in molecules that were 3-30-fold more potent at the P2Y2 receptor than P2Y4 receptor. 6-Aza-UTP was a P2Y2 receptor agonist that exhibited no activity at the P2Y4 receptor. Stereoisomers of UTPalphaS and 2'-deoxy-UTPalphaS were more potent at the P2Y2 than P2Y4 receptor, and the R-configuration was favored at both receptors. Molecular docking studies revealed that the binding mode of UTP is similar for both the P2Y2 and P2Y4 receptor binding pockets with the most prominent dissimilarities of the two receptors located in the second transmembrane domain (V90 in the P2Y2 receptor and I92 in the P2Y4 receptor) and the second extracellular loop (T182 in the P2Y2 receptor and L184 in the P2Y4 receptor). In summary, this work reveals substitutions in UTP that differentially affect agonist activity at P2Y2 versus P2Y4 receptors and in combination with molecular modeling studies should lead to chemical synthesis of new receptor subtype-selective drugs.     

BMAL1对H2O2诱导的H9C2心肌细胞损伤的影响及机制探讨

目的 探讨节律基因BMAL1对过氧化氢（H2O2）诱导的H9C2心肌细胞损伤的影响及机制。方法 构建 BMAL1稳定过表达的H9C2细胞系后,实验分为2个部分。（1）实验1。对照组、H2O2组（0.2 mmol/L的H2O2处理24 h）、 BMAL1 过表达（BMAL1-OE）组（BMAL1 稳定过表达 H9C2 细胞）、BMAL1 过表达+H2O2（BMAL1-OE+H2O2）组 （0.2 mmol/L的H2O2处理BMAL1稳定过表达H9C2细胞24 h）。（2）实验2。H2O2组、BMAL1-OE+H2O2组、BMAL1过表 达+抑制 NRF2+H2O2（BMAL1-OE+ML385+H2O2）组（NRF2 抑制剂 2 μmol/L 的 ML385 预处理 BMAL1 稳定过表达 H9C2 细胞 24 h,再用 0.2 mmol/L 的 H2O2处理 24 h）、BMAL1 过表达+抑制 HO-1+H2O2（BMAL1-OE+Znpp+H2O2）组 （HO-1抑制剂5 μmol/L的Znpp预处理BMAL1稳定过表达H9C2细胞24 h,再用0.2 mmol/L的H2O2处理24 h）。CCK-8 法检测细胞活力,羟胺法检测超氧化物歧化酶（SOD）活性、TBA 法检测丙二醛（MDA）含量,Western blot 法检测 BMAL1、核因子 E2 相关因子 2（NRF2）和血红素加氧酶-1（HO-1）蛋白表达水平。结果 （1）与 Control 组相比, BMAL1-OE组BMAL1 mRNA表达水平升高,H2O2组细胞活力和细胞上清液SOD活性下降、MDA含量增加,BMAL1、 NRF2和HO-1蛋白相对表达水平降低（P＜0.05）;与H2O2组相比,BMAL1-OE+H2O2组细胞活力和细胞上清液SOD活 性增加,MDA 含量减少,而 BMAL1、NRF2 和 HO-1 蛋白相对表达水平升高（P＜0.05）;（2）与 BMAL1-OE+H2O2组相 比,BMAL1-OE+ML385+H2O2组和BMAL1-OE+Znpp+H2O2组细胞活力和细胞上清液SOD活性降低,MDA含量增加 （P＜0.05）。结论 BMAL1可能通过上调NRF2/HO-1信号轴,减轻H2O2诱导的大鼠心肌细胞氧化应激损伤。     

MUSCLE VENOUS PO2 AND V.O2 ARE LINEARLY RELATED IN REPETITIVE TETANIC CONTRACTIONS OF CANINE MUSCLE DURING HYPOXIC HYPOXIA

1. It has previously been shown that perfusion with high O2-affinity-erythrocytes decreases venous PO2 (PVO2) and decreases O2 uptake (VO2) in contracting muscle at the same O2 delivery (arterial O2 concentration x flow). A linear VO2-PVO2 relationship has been obtained with a VO2-axis intercept, suggesting that, during this type of hypoxia, VO2 is composed of a PVO2-dependent and -independent VO2. However, the VO2-PVO2 relation during hypoxic hypoxia has not been examined. 2. To clarify this relation, PVO2 and VO2 have been measured in contracting gastrocnemius (1 Hz trains of 0.2 s isometric tetani) under both normoxic and hypoxic conditions during 5 min of stimulation. 3. Venous O2 changes proportionally with O2 delivery. Each VO2-PVO2 relation was linear, with the mean described by the equation VO2 = 5.06 + 0.41 x PVO2 (n = 6, r = 0.81, P < 0.05). The VO2-axis intercept was significantly different from zero (P < 0.05). 4. These results were similar to those obtained during hypoxia induced by high O2-affinity-erythrocytes. We conclude that there is a linear relationship between PVO2 and VO2 above the VO2-axis intercept, regardless of the type of hypoxia.     

Genetic polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian populations

AIMS: To investigate the distribution of cytochrome P450 2C9 (CYP2C9) and 2C19 (CYP2C19) genotype frequencies in the Beninese and Belgian Caucasian populations. METHODS: Beninese (n = 111) and Belgian (n = 121) were genotyped for CYP2C9*2, *3, *4, *5, and *11 as well as for CYP2C19*2 and*3. RESULTS: The distribution of alleles was: CYP2C9*1: 95.5 vs. 82.2% (P < 0.001); CYP2C9*2: 0 vs. 10% (P < 0.001); CYP2C9*3: 0 vs. 7.4% (P < 0.01); CYP2C9*4: both 0%; CYP2C9*5: 1.8 vs. 0% (P = 0.05); and CYP2C9*11: 2.7 vs. 0.4% (P < 0.05). The frequencies of the CYP2C19*2 allele were 13 vs. 9.1%, respectively. CYP2C19*3 was not detected in either population. The 95% confidence intervals for the differences of frequencies of CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*4, CYP2C9*5, CYP2C9*11, CYP2C19*1, CYP2C19*2 and CYP2C19*3 between Belgian and Beninese were 7%, 19%; - 14%, - 6%; - 11%, - 4%; - 1%, 1%; 0%, 4%; 0%, 5%; - 10%, 2%; - 2%, 10%; - 1%; respectively. The distributions of CYP2C9 genotypes in the Beninese and Belgian individuals were: CYP2C9*1/*1: 91 vs. 67% (P < 0.00001); CYP2C9*1/*2: 0 vs. 18.2% (P < 0.0001); CYP2C9*1/*3: 0 vs. 11.6% (P < 0.001); CYP2C9*1/*5: 3.6 vs. 0% (P = 0.05); CYP2C9*1/*11: 5.4 vs. 0.8% (P = 0.05); CYP2C9*2/*3: 0 vs. 1.6% (NS); CYP2C9*3/*3: 0 vs. 0.8% (NS). The distributions of CYP2C19 genotypes between these ethnic groups were: CYP2C19*1/*1: 73.9 vs. 83.5% (NS); CYP2C19*1/*2: 26.1 vs. 14.9% (P < 0.05); CYP2C9*2/*2: 0 vs. 1.6% (NS). CONCLUSIONS: Differences of allele frequencies between Beninese and Belgian populations were statistically significant for CYP2C9*2, *3, *5 and *11, but not for CYP2C9*4 or for CYP2C19*2 and *3.