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目的:分析CYP2C19*3基因多态性与癫痫患者奥卡西平(oxcarbazepine,OXC)活性代谢产物10,11-二氢-10-羟基卡马西平(monohydroxycarbazepine,MHD)血药浓度的相关性。方法:纳入120例OXC单药治疗1个月以上且症状控制良好的癫痫患者,采集清晨服药前空腹血,采用高效液相色谱法测定MHD稳态谷浓度。通过PCR和sanger测序判定患者CYP2C19*3基因型。结果:120例癫痫患者快代谢患者64例,MHD血浆浓度为(18.17±7.34)μg·mL-1;中代谢型患者36例,MHD血浆浓度为(19.31±9.17)μg·mL-1;慢代谢型患者20例,MHD血浆浓度为(25.79±7.51)μg·mL-1,3种基因型的MHD浓度有显著性差异(F=7.077,P=0.0013)。多因素分析显示,日剂量作为影响血药浓度的重要指标呈现出显著相关性(P<0.05)。结论:CYP2C19*3基因多态性影响MHD血药浓度,并且日剂量越高,MHD血药浓度越大,两者成显著正相关,临床应进行血药浓度监测。 相似文献
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Stephania Assimopoulos Nancy Shie Venkat Ramanan Xiuling Qi Jennifer Barry Bradley H. Strauss Graham A. Wright Nilesh R. Ghugre 《NMR in biomedicine》2021,34(1)
Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I ? HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2, T1), hemorrhage (T2*), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre‐ and post‐contrast T1) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2* values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia‐alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia‐alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high‐risk patients progressing towards heart failure. 相似文献
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目的研究在汉族人中拉莫三嗪相关过敏反应是否与HLA-B*1502有相关性。方法对在郑州人民医院诊断为癫痫的患者在服用拉莫三嗪前进行HLA-B*1502测定,将服用拉莫三嗪12周后出现过敏反应者作为实验组,未出现过敏反应者作为对照组1,服用其他非芳香族抗癫痫药物出现过敏反应者为对照组2,检测对照组2的HLA-B*1502阳性率,对3组间HLA-B*1502的阳性率进行比较。结果实验组HLA-B*1502的阳性率为41.86%,对照组1为14.02%,对照组2为13.33%.实验组阳性率高于对照组1(χ2=13.86,P<0.05)及对照组2(χ2=6.83,P=0.009),对照组1与对照组2比较差异无统计学意义(χ2=0.009,P=0.924)。结论HLA-B*1502可能与汉族人拉莫三嗪相关过敏反应相关。 相似文献
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"The Diseases of the Horny-coat of The Eye", known today as keratoconus, is a progressive, multifactorial, non-inflammatory ectatic corneal disorder that is characterized by steepening (bulging) and thinning of the cornea, irregular astigmatism, myopia, and scarring that can cause devastating vision loss. The significant socioeconomic impact of the disease is immeasurable, as patients with keratoconus can have difficulties securing certain jobs or even joining the military. Despite the introduction of corneal crosslinking and improvements in scleral contact lens designs, corneal transplants remain the main surgical intervention for treating keratoconus refractory to medical therapy and visual rehabilitation. To-date, the etiology and pathogenesis of keratoconus remains unclear. Research studies have increased exponentially over the years, highlighting the clinical significance and international interest in this disease. Hormonal imbalances have been linked to keratoconus, both clinically and experimentally, with both sexes affected. However, it is unclear how (molecular/cellular signaling) or when (age/disease stage(s)) those hormones affect the keratoconic cornea. Previous studies have categorized the human cornea as an extragonadal tissue, showing modulation of the gonadotropins, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Studies herein provide new data (both in vitro and in vivo) to further delineate the role of hormones/gonadotropins in the keratoconus pathobiology, and propose the existence of a new axis named the Hypothalamic-Pituitary-Adrenal-Corneal (HPAC) axis. 相似文献
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Perla Graciela Rodríguez Gutirrez Juan Ramn Gonzlez García Yolanda Alicia Castillo De Len Juan Rafael Zrate Guerrero María Teresa Magaa Torres 《Journal of clinical laboratory analysis》2021,35(3)
BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation. 相似文献
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目的:检测和分析消化系统恶性肿瘤患者UGT1A1*6、UGT1A1*28基因多态性。方法:收集186例消化系统恶性肿瘤患者血液标本,采用焦磷酸测序方法对UGT1A1*6、UGT1A1*28基因多态性进行检测,并对基因多态性频率进行统计分析。结果:186例消化系统恶性肿瘤患者样本具有群体代表性。UGT1A1*6基因多态性为野生型G/G占比63.4%、杂合型G/A占比32.8%、突变纯合型AA占比3.8%;UGT1A1*28基因多态性为野生型TA6/TA6占比75.8%、杂合型TA6/TA7占比21.5%、突变纯合型TA7/TA7占比2.7%;UGT1A1*6和*28基因多态性为野生型G/G且TA6/TA6占比48.9%,单点变异型G/G且TA6/TA7占比12.4%、G/A且TA6/TA6占比23.1%,双点变异型G/G且TA7/TA7占比2.2%、G/A且TA6/TA7占比9.1%、A/A且TA6/TA6占比3.8%,三点变异型G/A且TA7/TA7占比0.5%。患者UGT1A1*6与UGT1A1*28基因多态性频率分布之间具有显著性差异(P<0.05)。3个不同年龄段患者之间,胃癌、结直肠癌、其他消化系统恶性肿瘤患者之间的UGT1A1*28、UGT1A1*6和*28基因型分布具有显著性差异(P<0.05)。结论:消化系统恶性肿瘤患者应用伊立替康时,应联合检测UGT1A1*6和UGT1A1*28基因多态性,同时密切关注患者的肿瘤类型以及年龄差异。 相似文献