首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 93 毫秒
1.
目的 探讨5-羟色胺2C受体(5-hydroxytryptamine 2C receptor,5-HTR2C)基因-759C/T和-697G/C位点多态性对奥氮平治疗精神分裂症患者糖脂代谢的影响。方法 纳入184例接受奥氮平单一治疗的精神分裂症住院患者为研究对象,于基线及治疗第6周末测定患者空腹血糖(fastingbloodglucose,FBG)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)及高密度脂蛋白(high density lipoprotein,HDL)水平,运用多重高温连接酶检测反应技术检测5-HTR2C基因-759C/T–697G/C基因多态性,采用协方差分析比较不同基因型治疗前后糖脂水平的变化。结果 5-HTR2C基因–759C/T和–697G/C位点各基因型基线糖脂代谢指标差异无统计学意义;治疗6周后,–759C/T位点基因型间FBG和TG净增差异有统计学意义(F=4.862,P=0.009;F=3.397,P=0.036),其中FBG净增野生CC型患者高于CT或TT型患者(P=0.038,P=0.010),TG净增野生CC型患者高于TT型患者(P=0.010);–697G/C位点基因型间FBG净增差异有统计学差异(F=4.385,P=0.014),其中野生GG型患者高于CC型患者(P=0.006);两位点联合分析也发现,野生CC/GG基因型患者FBG净增高于CT+TT/GC+CC基因型患者(P=0.021)。结论 5-HTR2C基因–759C/T和–697G/C位点多态性与奥氮平治疗精神分裂症患者引起糖脂代谢异常具有一定相关性。  相似文献   

2.
目的 建立准确、快速、经济的方法,检测NUDT15 c.415C>TTPMT*3C基因多态性,探讨临床应用价值。方法 收集2017年5月-2018年5月期间福建汉族患者服用硫唑嘌呤2周以上的血清样本,提取DNA或白细胞后分别采用PCR-RFLP法、PCR-Sanger测序法和荧光定量PCR法对NUDT15 c.415C>TTPMT*3C进行基因多态性分型,比较这3种方法的准确性、简便性及经济性。根据白细胞值分组,结合临床资料,探讨基因多态性等因素与硫唑嘌呤致白细胞减少的相关性。结果 共纳入129例患者,其中硫唑嘌呤致白细胞减少15例(11.6%)。3种方法的基因多态性检测结果一致,TPMT*3C未发现突变纯合子。携带NUDT15c.415C>T突变等位基因者服用硫唑嘌呤致白细胞减少的风险高于携带野生等位基因者(OR=6.2,95%CI:2.5~15.4,P=0.000 054),而携带TPMT*3C突变等位基因者与野生等位基因者出现白细胞减少比例并无显著性差异(P=0.393)。NUDT15c.415C>T基因多态性预测白细胞减少敏感度为53.3%,特异度为85.1%,ROC曲线AUC为0.69。结论 3种方法都可用于临床检测NUDT15 c.415C>TTPMT*3C基因多态性。PCR-RFLP法不需要专用试剂盒,也不需要昂贵的仪器设备,成本较低,过程简单,易于操作,特别适合条件有限的单位开展工作。福建汉族患者在服用硫唑嘌呤前进行NUDT15c.415C>T基因多态性检测比TPMT*3C更具临床价值。  相似文献   

3.
目的 应用meta分析证实靶基因的多态性是否与糖皮质激素诱导性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)发生相关。方法 检索PubMed、Embase、The Cochrane Library、Clinical Trial、CBM、万方、维普和CNKI等数据库中已发表的文章以获得适宜的研究,并以固定或者随机效应模型计算最终的OR值和95%置信区间(95%CI)。结果 检索共发现有37项研究包含41个与SONFH发生风险相关的基因多态性位点。选择含有≥3个适宜研究的多态性位点进入meta分析,纳入的多态性位点主要集中在3个基因即PAI-1MTHFRABCB1。携带有PAI-1突变基因5G的患者应用糖皮质激素后易发生SONFH,但差异不具有统计学意义[OR=0.95,95%CI(0.54,1.67),P=0.85]。SONFH发生率在MTHFR突变型和野生型之间差异存在统计学意义[OR=0.69,95%CI(0.50,0.95),P=0.02],携带有MTHFR 677T的患者较易发生SONFH。携带ABCB1 3435C等位基因者发生SONFH的风险更高,具有显著的统计学差异[OR=1.40,95%CI(1.11,1.76),P=0.005];而ABCB1 G2677T/A位点的基因多态性与SONFH发生之间无明显的统计学差异[OR=1.32,95%CI(0.76,2.28),P=0.32]。结论 MTHFR C677TABCB1 C3435T基因的多态性与股骨头坏死的发生风险显著相关。  相似文献   

4.
目的 探讨有机阴离子转运体1B3(solute carrier organic anion transporter family, member 1B3,SLCO1B3)基因多态性对狼疮性肾炎患者吗替麦考酚酯(mycophenolate mofetil,MMF)药效学的影响。方法 以2019年9月—2021年4月于揭阳市人民医院就诊的新确诊的或既往确诊的狼疮性肾炎患者为研究对象。受试者均使用MMF治疗,且总疗程≥12个月,综合评估MMF的疗效。采用Agena MassARRAY®方法检测受试者SLCO1B3 334T>G/699G>A (rs4149117/rs7311358)基因型,应用SPSS 25.0软件分析基因多态性与MMF药效学的相关性。结果 SLCO1B3 334T>G/699G>A基因型频率符合Hardy-Weinberg 平衡。334GG/699AA携带者MMF疗效差的几率显著高于334TT/699AA和334TG/699GA携带者(P<0.001);Logistics回归显示334GG/699AA和尿蛋白>2.5 g·(24 h)-1是MMF疗效差的危险因素[OR=4.038(1.731,9.420),P<0.001;OR=4.157(1.705,10.137),P=0.002]。经过联合分析表明,携带334GG/699AA型且尿蛋白>2.5 g·(24 h)-1的患者疗效差的风险是非334GG/699AA携带者的8.563倍[(3.301,22.216),P<0.001]。结论 SLCO1B3 334T>G/699G>A与狼疮性肾炎患者MMF疗效有关,334GG/699AA携带者MMF疗效差的可能性更高。  相似文献   

5.
目的 系统评价5-HTR2A 102T>C基因多态性与抗精神病药物疗效的相关性。方法 计算机检索Web of Science、PubMed、中国学术期刊全文数据库(CNKI)、万方数据库、维普数据库中研究5-HTR2A 102T>C基因多态性与抗精神病药物疗效的研究,检索年限从建库至2017年5月2日。按纳入与排除标准筛选文献、提取资料并评价纳入研究的方法学质量后,采用Stata 12.0软件进行Meta分析。结果 共纳入10项研究,Meta-分析结果表明,5-HTR2A 102T>C基因多态性与抗精神病药物疗效在等位基因模型、共显性基因模型、显性基因模型中均无统计学意义(P>0.05):等位基因模型OR=1.16,95% CI(1.00~1.36);共显性基因(TT vs CC)模型OR=1.23,95% CI(0.91~1.65);共显性基因(TT vs TC)模型OR=0.90,95% CI(0.68~1.19);显性基因模型OR=1.04,95% CI(0.80~1.34);而隐性基因模型和超显性基因模型具有统计学意义(P<0.05):隐性基因模型OR=1.37,95% CI(1.09~1.72);超显性基因模型OR=0.78,95% CI(0.62~0.96)。结论 5-HTR2A 102T>C基因多态性与抗精神病药物疗效有关联性。  相似文献   

6.
目的 综述NUDT 15基因多态性与巯嘌呤类药物耐受性及其所致白细胞减少的研究,以期为巯嘌呤类药物在临床中的应用提供参考。方法 检索国内外相关文献,进行整理和综合分析。结果 研究人群主要集中在亚洲,大多为韩国和日本人,在中国儿童急性淋巴细胞白血病患者中仅有2个人群的研究,在中国炎症性肠病患者中有3个相关研究。大多数研究显示在亚洲人群中NUDT 15 c.415 C>T位点突变与巯嘌呤类药物的耐受性及相关白细胞减少有关,此外多个在炎症性肠患者群中的研究发现c.415 C>T纯合突变可能与严重脱发有关。结论 大多数研究显示亚洲人群NUDT 15 c.415 C>T位点突变与巯嘌呤类药物的耐受性及相关白细胞减少有关,该位点的测定可能会优化巯嘌呤类药物在临床中的应用,但其他NUDT 15基因位点突变相关的研究较少,还需要进一步探究。  相似文献   

7.
目的 探讨亚甲基四氢叶酸还原酶(MTHFR)C677T与A1298C基因多态性在卡培他滨治疗中晚期结直肠癌(CRC)患者的安全性及有效性,为临床诊治CRC提供理论依据。方法 收集经病理诊断确诊的中晚期结直肠癌患者50例,用实时荧光定量PCR仪进行MTHFR C677T与A1298C基因多态性检测,观察不同基因型之间安全性及有效性的差异。结果 MTHFR C677T的CC、CT、TT基因型频率分别为46%、40%、14%,TT基因型恶心呕吐的发生率及有效率高于CC与CT基因型,差别具有统计学意义(P<0.05)。MTHFR A1298C的AA、AC、CC基因型频率分别为60%、34%、6%,CC基因型腹泻发生率高于AA与AC基因型,差别具有统计学意义(P<0.05),MTHFR A1298 C中各基因型有效率差异无统计学意义。结论 MTHFR C677T与MTHFR A1298C基因多态性在卡培他滨治疗CRC患者具有较好的临床意义,但MTHFR A1298C与药物治疗有效率无关。  相似文献   

8.
周瑞瑜  吴立强  罗以 《肿瘤药学》2022,12(3):387-390
目的 研究BRAF V600E基因突变能否成为乳头状甲状腺癌(PTC)预后相关分子标志物,从而更有利于PTC的个体化治疗。方法 收集远处转移的高分化乳头状甲状腺癌患者的肿瘤组织标本共30例,运用扩增受阻突变系统(ARMS)法进行BRAF基因检测。结果 BRAF基因突变率为36.67%(11/30),均为V600E突变;BRAF V600E基因突变与患者性别、有无淋巴结转移、远处转移情况、肿瘤病理类型及大小均无明显相关性(P>0.05),而与患者年龄(≥45岁)显著相关(P=0.025);BRAF突变型患者的无进展生存时间(PFS)更长(P=0.05)。结论 BRAF突变型远处转移高分化乳头状甲状腺癌患者可能预后更好。  相似文献   

9.
王卉  李广  刘国炳 《肿瘤药学》2021,11(5):570-576
目的 通过深度挖掘Oncomine数据库中的基因信息,分析FAM20基因家族在宫颈癌中的表达及其作用机制。方法 通过Oncomine数据库查找有关于FAM20基因家族的研究信息,并对其在宫颈癌中的表达进行初步分析,根据分析结果,在Oncomine数据库中摘录所选取的FAM20家族成员在宫颈癌中的生存信息,使用GraphPad Prism软件进行生存分析,根据结果探讨其临床意义,发现FAM20基因家族中仅FAM20C基因对宫颈癌患者的生存率有意义,再使用TCGA数据库对FAM20C基因在宫颈癌中的表达及生存信息进行验证。用cBioPortal分析FAM20C基因相关蛋白功能及途径富集,通过String构建FAM20C基因的相关蛋白网络图,分析蛋白富集的生理过程。结果 在Oncomine数据库中共收集33项FAM20家族成员在肿瘤组织及正常组织中表达差异的研究。对不同成员进一步分析发现,FAM20BFAM20C在宫颈癌中的表达存在差异(P<0.05)。对FAM20BFAM20C基因在Oncomine数据库中的表达情况及生存数据做进一步分析,发现FAM20C高表达时患者生存率降低(P<0.05),与TCGA数据库所验证的结果大体相同。通过Genecards数据库收集到FAM20C相关蛋白DMP1、AMELX、AMBN、MEPE、ENAM、FGF23、AMTN、SPP1、AHSG,主要富集于牙齿及骨组织的发育调控、柱状上皮细胞的分化调控以及细胞黏附过程。结论 FAM20C基因可通过影响肿瘤细胞的迁移和侵袭,对宫颈癌患者的生存产生影响。同时,靶向FAM20C基因可能是宫颈癌潜在的诊断和治疗方法。  相似文献   

10.
目的 研究维生素D受体(vitamin D receptor,VDR)基因多态性对肾移植术后早期他克莫司浓度的影响。方法 以360例使用他克莫司联合霉酚酸类药物以及糖皮质激素三联抗排异方案的肾移植患者为研究对象,检测患者CYP3A5 (rs776746)、VDR(VDR ApaI rs7975232,VDR BsmI rs1544410,VDR FokI rs2228570VDR TaqI rs731236)基因型,比较分析不同基因型患者肾移植术后7 d时他克莫司血药浓度(concentration,C)、剂量(dose,D)以及浓度剂量比(ratio of concentration to dose,C/D)的差异。结果 CYP3A5非表达组(GG型)患者他克莫司的C和C/D均显著高于CYP3A5表达组(AA和AG型)(P<0.05)。以CYP3A5基因型进行分层后,在CYP3A5非表达组中VDR ApaI rs7975232 AA型患者C/D显著低于AC和CC型患者(P<0.05),然而在CYP3A5表达组中VDR ApaI rs7975232各基因型的C和C/D差异无统计学意义。此外,无论在CYP3A5表达组还是非表达组中,VDR BsmI rs1544410,VDR TaqI rs731236VDR FokI rs2228570各基因型之间他克莫司的C、D和C/D差异均无统计学意义。结论 VDR ApaI rs7975232基因多态性与CYP3A5非表达组肾移植患者早期他克莫司血药浓度具有相关性,该基因型检测可能有助于指导肾移植患者他克莫司个体化用药。  相似文献   

11.
Mink and otters are valuable wildlife resources and management efforts in North America and Europe have been directed towards re-establishing extirpated populations or expanding existing populations. The similarity of otter and mink habits and trophic status may allow inferences about the suitability of the habitat that is occupied by one species (mink) for the other species that is absent (otter). Remnant otter populations in Illinois have not expanded even though suitable habitat appears to be available and is occupied by mink. Low contaminant concentrations in tissues of mink trapped in a habitat where otters are not found and metal and organochlorine concentrations in tissues of otters incidentally collected by the Illinois Department of Natural Resources, suggest that environmental contaminants should not hinder natural expansion of otters in Illinois.  相似文献   

12.
目的 找出巴西龟特征肽段,建立龟甲(浙龟甲)中掺入巴西龟的专属性检查方法。方法 样品以水提法提取,胰蛋白酶酶解,利用超高效液相色谱-四级杆飞行时间质谱和数据处理软件查找巴西龟特征肽,并利用蛋白质搜库技术初步测序;利用找到的特征肽段,建立超高效液相色谱-串联四级杆质谱的多反应监测的巴西龟掺伪专属性检查方法。结果 找出巴西龟特征性肽段m/z 400.23(双电荷),并初步测定序列,通过分析该特征肽段二级质谱图,确定了专属性检测离子对m/z 400.23(双电荷)→374.05,142.90,并建立了龟甲(浙龟甲)中掺入巴西龟的专属性检查方法。20批样品中,11批样品检出巴西龟成分。结论 该方法的专属性强,符合分析检测的方法技术要求,可用于龟甲(浙龟甲)掺入巴西龟的检查。  相似文献   

13.
日本血吸虫雄虫在4℃或37℃的HBS及无45Ca2+的HBS中经吡喹酮1或30μg/ml作用0.5~2h后,未见虫的Ca2+,Mg2+含量有明显变化,但除4℃的HBS组外,余2组虫的K+含量明显减少,而虫的Na+含量的增加则不明显。在含30 mM Mg2+的HBS中,雄虫经吡喹酮作用1h后,虫的Mg2+含量明显增加。在37℃的HBS中,血吸虫雄虫经吡喹酮1μg/ml作用5~60min后,虫的皮层胞质中的452+含量的百分比较各相应对照组的明显减少,而虫体肌肉的则相反。在4℃的HBS或无45Ca2+的HBS中,吡喹酮对452+在虫体内的分布无明显影响。  相似文献   

14.
Objectives  The aims of this study were to characterize the population frequency of PEPT2 (SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects. Methods   PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally) pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were subsequently genotyped for their PEPT2 polymorphisms. Results  In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and 0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C max of cephalexin was significantly lower in the Chinese (29.80 ± 4.09 μg ml−1) population than in the Asian Indian one (33.29 ± 4.97 μg ml−1; P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups. Conclusion   PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are needed.  相似文献   

15.
黄媛  李宁  李铣  高璐莎  孟大利 《药学学报》2008,43(3):277-280
为了研究西洋参茎叶总皂苷氧化碱解产物的组成,对加拿大产西洋参茎叶总皂苷进行氧化碱解后,其产物通过硅胶柱色谱、Sephadex LH-20柱色谱、重结晶等方法进行分离纯化得到2个化合物。根据化合物的理化性质和光谱数据,鉴定其结构为:(12R,20S,24R)-20,24;12,24-diepoxy-24-deisopropyl-dammarane-3β-ol (1)和(20S,24R)-20,24-epoxydammarane-3β,12β,25-triol (2)。化合物1,2均为首次从西洋参茎叶总皂苷碱解产物中分离得到侧链环合的达玛烷型三萜,其中化合物1为新化合物。  相似文献   

16.
Summary The plasma kinetics of 5,6-dihydro-5-azacytidine (DHAC) was determined in mice using an HPLC method following an intravenous dose of 2000 mg/kg (LD10). Pharmacokinetic parameters calculated from these single dose data were sufficient to predict steady state plasma concentrations produced by s.c. infusion of DHAC. Lethal toxicity (LD66) occurred at an infusion rate of 37 mg/kg/h (111mg/m2/h), corresponding to a plasma steady-state DHAC concentration 38 ± 14 g/ml when the infusion time was 96 h; no lethality occurred at infusion times of 72 h or less. In vitro clonogenic assays and in vivo therapeutic experiments with L1210 tumor indicated that increasing the exposure time at concentrations near 25 g/ml from 24 to 72 h increased the cell kill only slightly. The maximum log cell kill of L1210 estimated from either in vitro or in vivo data was 1.5 logs.  相似文献   

17.
Summary The cyclic AMP responses to norepinephrine (NE) in slices of the rat limbic forebrain after the administration of (S)-amphetamine and the role of its para- and -hydroxylated metabolites were investigated. The chronic but not acute administration of (S)-amphetamine to rats causes a significant reduction in the sensitivity of the cyclic AMP generating system to NE without changing the basal level of the nucleotide. This change in the sensitivity of the system is not associated with a change in the EC50 value for NE but reflects mainly a decrease in the maximal response. After withdrawal of the drug, the cyclic AMP response to NE returned to control values within 4 days. In vitro, (S)-p-hydroxyamphetamine (POH) and all stereoisomers of p-hydroxynorephedrine (PHN) except (S,R)-PHN enhanced the cyclic AMP response to low concentrations of NE. Since (S,R)-PHN [like the other stereoisomers of PHN and (S)-POH] inhibited in a dose-dependent manner the high affinity uptake of 3H-NE into crude synaptosomal fractions of the limbic forebrain, the results might suggest that the presumably physiological enantiomer of PHN also exerts receptor blocking properties. The inhibition by (S,R)-PHN of the cocaine induced potentiation of the cyclic AMP response to NE supports this supposition. The results provide evidence that the hydroxylated metabolites of (S)-amphetamine, (S)-POH and (S,R)-PHN, modify the action of the parent drug on central noradrenergic function at the level of the NE receptor coupled adenylate cyclase system.  相似文献   

18.
蓝萼甲素(glaucocalyxin A,GLA)是一种具有对映15-氧-16贝壳杉烯(ent-15-oxo-16-kaurene)骨架结构的二萜类化合物。其具有心血管保护、内皮保护、抗凝血、抗乙肝病毒、抗肿瘤、抑菌、抗炎、耐缺氧、免疫抑制及调节钙离子浓度等多种药理作用,并且有很高的体内安全性。民间常用蓝萼香茶菜治疗肝炎、胃炎、乳腺炎、腹痛、关节痛等疾病,临床上蓝萼香茶菜主要用于治疗冠心病、心绞痛、脑供血不足等缺血、缺氧性心脑血管疾病。本研究将对蓝萼甲素的药理作用及其机制和毒理学作用做一总结。  相似文献   

19.
The many limitations in determining the pharmacokinetic parameters of firstorder invasion of, and elimination from, the onecompartment body model by the method of residuals or by feathering Ct data can be minimized by applying the simplified methods outlined herein. Comparisons of the apparent volumes of distribution, V, calculated on the premises that the Bateman Function represents ka>ke or its converse, ke>ka,i.e., flip-flop, can permit a proper choice of the correct version. Estimation of ke can be obtained by regression of (A0/V)/C(oncentration) on AUC1/ Cwhere A0/Vis estimable from knowledge of Cmax and tmax since .The ratio of the magnitude of the rate constant of invasion to that of elimination, m=ka/ke,is related to ketmax by the expression ketmax=ln m/ (m–1)for all possible values of m.A table for the determination of m from values of ketmax is given. When bioavailability, =A0/Dose,is known or complete, ke and Vcan be determined from the respective ordinate and abscissa of the intersection of and Cl(clearance)/ke,both plotted against arbitrary ke values. The two functions may not intersect at low values of mdue to errored C-t values but the ke value when the two curves are closest (kmin)may approximate ke.The intersections of and keAUCT (AUCtrap)plotted against variable ke values (Method A) provide estimates of ke from their abscissa values and A/Vfrom their ordinate values when is unknown. Method B appears to give more reliable estimates of ke at the kmin of the difference plotted against ke.Since kmin of this plot is 1/tmax when m=1,the identity of the mas unity underlying the C-t data is indicated when either kmintmax is approximately unity or kmin ispractically synonymous with 1/tmax.This was clearly shown when 12 constructed m=1,C-t cases with 10% random error were evaluated by Method B. Better estimates were effected by all procedures when the raw C-t data were smoothed.We regretfully announce that Dr. Edward Garrett passed away on October 25, 1993, after an extended illness.  相似文献   

20.
目的建立茚三酮柱后衍生化氨基酸分析仪测定N(2)-L-丙氨酰-L-谷氨酰胺(L-Ala-L-Glu)含量的方法。方法根据L-Ala-L-Glu与茚三酮反应后溶液在570nm处有最大吸收的原理,以钾钠缓冲液为流动相,将L-Ala-L-Glu洗脱后,与茚三酮进行柱后衍生反应,生成可以被分光光度计检测的有色物质,氨基酸分析仪测定L—Ala-L-Glu的含量。结果L-Ala-L-Glu在1-20mg·L^-1、内线性关系良好(r=0.9979),低、中、高3种浓度的回收率分别为94.5%,97.6%和98.7%;RSD分别为0.52%,0.10%和O.06%。结论本法操作简单,分离度良好,结果准确可靠,可用于L-Ala-L-Glu的含量测定。  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号