LC-MS测定埃博霉素B血浆蛋白结合率

目的 建立液相色谱串联质谱(LC-MS)测定方法并检测犬以及人体埃博霉素B的血浆蛋白结合率.方法 建立LC-MS联合检测方法,以犬和人体血浆为对象,结合甲衡透析法检测埃博霉素B的血浆蛋白结合率.结果 3种浓度(100、50和10 ng/mL)埃博霉素B与犬血浆蛋白结合率分别为(85.4％±2.5％)、(81.3％±2.2％)和(83.7％±3 4％),与人体血浆蛋白结合率分别为(74.4％±3 8％)、(81.0％±2.9％)和(75.6％±2.2％),且灵敏度高,重现性好,操作简单.结论 埃博霉素B血浆蛋白结合率高,LC-MS可用于埃博霉素B血浆蛋白结合率的检测.     

Do schizophrenia and bipolar disorders share a common disease susceptibility variant at the MMP3 gene?

There is growing evidence of partial etiological overlap between schizophrenia (SZ) and bipolar I disorder (BD-I) from linkage analysis, genetic epidemiology and molecular genetics studies. SZ and BD-I are neurodevelopmental disorders with genetic and environmental etiologies. Recent studies have demonstrated that matrix metalloproteinase 3 (MMP3) is a key event in associative memory formation, learning and synaptic plasticity, which are important in psychiatric disorders. In the light of these findings, we analyzed the genetic variations in the MMP3-1171 5A/6A in patients with SZ, patients with BD-I and healthy controls. To the best of our knowledge, this is the first study to report an association of variation in gene encoding MMP3 with SZ. Our study group consisted of 111 unrelated patients with SZ, 141 unrelated patients with BD-I, and 121 unrelated healthy controls. The frequencies of 6A6A genotype and 6A allele distributions of MMP3 in patients with SZ were significantly decreased when compared with controls. In contrast, in patients with SZ, the distributions of 5A5A genotype and 5A allele of MMP3 gene were significantly increased as compared with healthy controls. When the frequencies of genotypes or alleles in schizophrenic patients and bipolar patients were compared, 6A6A genotype and 6A allele in patients with BD-I were significantly higher than patients with SZ. In contrast, 5A5A genotype and 5A allele distributions of MMP3 gene were significantly frequent in patients with SZ. On the other hand, no significant differences were found in the allele or genotype distribution in patients with BD-I compared with controls. In conclusion, our data have supported the hypothesis that there is a possible relationship between − 1171 5A/6A polymorphism of MMP3 gene and SZ. A larger sample group is needed to confirm the potential role of this gene in the pathophysiology of psychiatric disorders.     

利用紫外分光光度法测定罗格列酮游离碱的pKa值

目的:建立测定胰岛素增敏剂罗格列酮游离碱电离平衡常数值的方法并测定罗格列酮游离碱的电离平衡常数.方法:将pH1.64、5.76、6.41、6.91、7.14、7.46、10.64的罗格列酮游离碱甲醇溶液分别在200～400 nm处扫描,并在选定波长312、317、326、330 nm处测定其吸收度,得到岁格列酮游离碱电离平衡常数值.结果:罗格列酮游离碱的pKa值为7.09.结论:该方法简便易行,适用于测定酸碱pKa值在2～9之间的药物.     

Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population

Reactive oxygen species (ROS)-mediated damage has been hypothesized to play a role in the development and poor outcome of schizophrenia, as well as the development of neuroleptic-induced abnormal involuntary movements. Recently, the functional polymorphism (Ala-9Val) in the manganese superoxide dismutase (MnSOD) gene (part of the antioxidant defense mechanism) was found to be associated with schizophrenia in a Turkish population. This study was aimed at replicating this finding in a Xhosa population. In addition, the role of Ala-9Val in abnormal involuntary movement and tardive dyskinesia development in the Xhosa population was also investigated. The schizophrenic patient group (n=286) and a healthy control group (n=243) were genotyped for the Ala-9Val polymorphism using heteroduplex-single stranded conformational polymorphism (HEX-SSCP) analysis. No significant difference in genotype or allele frequency could be observed between the schizophrenia and control group (P=0.294 and P=0.528 respectively). In addition no association could be found between the polymorphism and symptom severity (SANS and SAPS). The Xhosa schizophrenia patient group with abnormal involuntary movements (n=54) and a subgroup with tardive dyskinesia (n=30) was found to significantly differ in Ala-9Val genotype frequency (P=0.008 and P=0.011 respectively) compared to the Xhosa schizophrenia patient group without abnormal involuntary movements (n=204). However, no significant difference was found for the allele frequencies (P=0.955 and P=0.161). Further, using ANCOVA no association was found between AIMS score and genotype in the group with abnormal involuntary movements (P=0.1234). However, in the patient group with tardive dyskinesia an association was observed between genotype and AIMS score (P=0.0365). These results do not support a major role of the MnSOD Ala-9Val polymorphism in the development of schizophrenia or symptom severity in the Xhosa population. Yet it seems to be involved in the development of abnormal involuntary movements and tardive dyskinesia and may even modulate the severity of tardive dyskinesia.     

血清尿素参考方法的建立以及临床常用试剂盒的比对研究

目的建立血清尿素测定的酶偶联平衡的参考方法(紫外分光光度法),对此方法进行性能验证,并评价4种临床常用的试剂盒是否可以接受。方法以美国CDC推荐的血清尿素酶偶联平衡候选参考方法为依据建立本实验的参考方法;通过测定标准物质(SRM909b),以及参加RELA-2009比对实验(ring-tiral),来验证参考方法的准确性;按CLSI《EP9-A2》要求,以酶偶联平衡参考方法作为比对方法,4种临床常用的检测试剂盒为待评方法,对40份血清样品的结果进行分析比较。结果用酶偶联平衡参考方法测定SRM909b水平1和2,与靶值的偏倚分别为2.19%,0.24%;参加参考实验室国际比对,血清尿素结果在可接受范围内;4种常用的试剂盒在医学决定点(Xc=9.64 mmol/L)预期偏差的95%可信区间值在实验室定义的可接受偏差(4.5%)范围内,也在生物学变异的可接受偏差(5.5%)范围内。结论本室已建立并验证了血清尿素测定的酶偶联平衡参考方法;4种常用血清尿素试剂盒的测定结果与参考方法的测定结果存在差异,但误差在临床可接受范围。     

高效液相色谱法测定间尼索地平不同对映体在血浆中的蛋白结合率

目的:建立间尼索地平不同对映体在大鼠血浆、人血浆和牛血清白蛋白中蛋白结合率的测定方法,并计算不同种属血浆蛋白的相关参数。方法:采用平衡透析法测定蛋白结合率,用高效液相色谱法测定血浆中药物总浓度及游离药物浓度。结果:R-与S-间尼索地平的血浆蛋白结合率分别为:大鼠血浆为(97.4±8.2)%、(93.0±13.4)%;人血浆为(90.8±10.5)%、(89.2±9.9)%;牛血清白蛋白为(95.3±8.7)%、(91.0±5.7)%。最低定量下限为0.01ng。结论:在体外间尼索地平不同对映体与大鼠血浆、人血浆和牛血清白蛋白结合率很高,R-间尼索地平的结合率及蛋白结合药物的表观最大能力βp均较S-间尼索地平高。随着药物血浆浓度升高,R-间尼索地平结合率下降,S-间尼索地平结合率升高,均有一定的浓度依赖性。     

Support for a reduction in the number of trials needed for the star excursion balance test

Robinson RH, Gribble PA. Support for a reduction in the number of trials needed for the Star Excursion Balance Test.

Objective

To determine the number of trials necessary to achieve stability in excursion distance and stance leg angular displacement for the 8 directions of the Star Excursion Balance Test (SEBT).

Design

One-way repeated-measures analysis of variance.

Setting

Athletic training laboratory.

Participants

Twenty participants (10 men, 10 women) without any known musculoskeletal injuries or neurologic deficits that could have negatively affected their dynamic balance volunteered for the study.

Intervention

Participants completed 6 practice and 3 test trials in each of the 8 reach directions of the SEBT.

Main Outcome Measures

Excursion distances of the reaching leg normalized to leg length and angular displacement at the hip and knee of the stance leg in all 3 planes of movement were determined.

Results

There were significant increases in excursion distance, hip flexion, and knee flexion for 7, 4, and 5 of the 8 reach directions, respectively.

Conclusions

For the majority of the reach directions, maximum excursion distances and stance leg angular displacement values achieved stability within the first 4 practice trials, thus justifying a reduction in the recommended number of practice trials from 6 to 4 and supporting the trend toward simplifying SEBT administration.     

A likelihood ratio test of population Hardy‐Weinberg equilibrium for case‐control studies

Testing Hardy‐Weinberg equilibrium (HWE) in the control group is commonly used to detect genotyping errors in genetic association studies. We propose a likelihood ratio test for testing HWE in the study population using both case and control samples. This test incorporates underlying association models. Another feature is that, when we infer the disease‐genotype association, we explicitly incorporate HWE or a possible departure from Hardy‐Weinberg equilibrium (DHWE) into the model. Our unified framework enables us to infer the disease‐genotype association when a detected DHWE needs to be part of the model after causes for the DHWE are explored. Real data sets are used to illustrate the application of the methodology and its implication in genetic association studies. Our analysis and interpretation touch on issues such as genotyping errors, population selection, population stratification, or the study sampling plan, that all could be the cause of DHWE. Genet. Epidemiol. 2009. Published 2008 Wiley‐Liss, Inc.     

Genetics of Lesch's typology of alcoholism

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.     

Is there protective haplotype of dysbindin gene (DTNBP1) 3 polymorphisms for major depressive disorder

Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.