甲状腺素运载蛋白时间分辨免疫荧光试剂盒的制备和效能评价

目的制备甲状腺素运载蛋白(transthyretin,TTR)的时间分辨免疫荧光(time-resolved fluoroimmunoassay,TRFIA)试剂盒并对其性能进行评价。方法将抗TTR的4H2单克隆抗体作为包被抗体包被至96孔板,用Eu^3+标记3E4单克隆抗体作为检测抗体,制备双抗体夹心TRFIA试剂盒,应用该试剂盒对42例川崎病(Kawasaki disease,KD)患儿及13名健康儿童的血清进行检测,以稀释回收率、准确度、精密度、稳定性等指标对试剂盒的效能进行评价。结果该研究制备的TTR TRFIA试剂盒与Western blot法同时检测42份KD临床样本和13份健康样本,两方法的结果符合率为100%,特异性强。试剂盒的最低检出浓度为0.05μg/ml,稀释回收率为88.00%~111.00%,分析内精密度为8.01%~9.17%,分析间精密度为8.88%~11.82%。稳定性实验表明该试剂盒可在4℃稳定保存6个月,37℃稳定保存7 d。结论该研究制备的TTR TRFIA试剂盒具有准确性高、方便快捷等优点,适用于大批量临床KD血清样品的TTR检测,为快速区分丙种球蛋白敏感型和无反应型的KD患儿提供了方法。     

Atrial Fibrillation and Cognitive Function: JACC Review Topic of the Week

Numerous vascular risk factors and vascular diseases contribute to cognitive impairment and dementia. Many studies and registries show an association of atrial fibrillation (AF) with cognitive impairment, cognitive decline, and dementia. This is true for vascular dementia and Alzheimer's disease. The assumed multifactorial mechanisms include ischemic stroke, both apparent and silent, cerebral microinfarcts, cerebral hemorrhage, and reduced cerebral blood flow. A number of retrospective observational and prospective studies support that anticoagulation in patients with AF may reduce the risk of cognitive decline and dementia. This holds for both vitamin K antagonists (e.g., warfarin) and direct oral anticoagulants. However, it still remains unproven if anticoagulation reduces cognitive decline and dementia in AF patients based on randomized trials.     

Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study#

Objective: To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers.

Methods: A phase IIa proof-of-concept trial included two phases separated by a 6-week washout period. Phase A: single 200?mg dose of tolcapone; phase B: three 100?mg doses taken at 4?h intervals. The primary efficacy variable was TTR stabilization.

Results: Seventeen subjects were included (wild type, n?=?6; mutation TTR Val30Met, n?=?11). TTR stabilization was observed in all participants. Two hours after dosing, 82% of participants in phase A and 93% of those in phase B reached a TTR stabilization value of at least 20%. In phase A, there was an increase of 52% in TTR stabilization vs baseline values 2?h after dosing, which decreased to 22.9% at 8?h. In phase B, there was a significant increase of 38.8% in TTR stabilization 2?h after the first 100?mg dose. This difference was maintained after 10?h and decreased after 24?h. No serious adverse events were observed.

Conclusions: The ability of tolcapone for stabilizing TTR supports further development and repositioning of the drug for the treatment of ATTR amyloidosis.

EudraCT trial number: 2014-001586-27

ClinicalTrials.gov Identifier: NCT02191826     

Advanced glycation end product in familial amyloidotic polyneuropathy (FAP)

Abstract. Nyhlin N, Ando Y, Nagai R, Suhr O, El Sahly M, Terazaki H, Yamashita T, Ando M, Horiuchi S (Umeå University Hospital, Umeå, Sweden and Kumamoto University School of Medicine, Kumamoto, Japan). Advanced glycation end product in familial amyloidotic polyneuropathy (FAP). J Intern Med 2000; 247 : 485–492. Objectives. Advanced glycation end products (AGE) are present in amyloid deposits in β₂‐microglobulin amyloidosis, and it has been postulated that glycation of β₂‐microglobulin may be involved in fibril formation. The aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP). Setting. Department of Medicine, Umeå University Hospital and First Department of Internal Medicine, Kumamoto University School of Medicine. Design. The presence of AGE was sought immunohistochemically and biochemically in amyloid‐rich tissues from patients with FAP. Subjects. Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous samples from three FAP patients were used. Results. Immunohistochemical studies using a polyclonal anti‐AGE antibody revealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non‐amyloid associated immunoreactivity was also observed in a few regions of the specimens, although the AGE‐positive structures were situated in areas containing amyloid deposits. Western blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils. Conclusion. The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP.     

Asp58Ala is the Predominant Mutation of the TTR Gene in Korean Patients with Hereditary Transthyretin‐Related Amyloidosis

Hereditary transthyretin (TTR)‐related amyloidosis (ATTR) seems to be a rare autosomal‐dominant inherited form of systemic amyloidosis. Studies indicate considerable heterogeneity in the disease's presentation and genotype; however, there is little data from Korea, where the prevalence of hereditary ATTR is very low. In this study, we investigated the phenotypic and genotypic spectra of hereditary ATTR in Korea. Direct sequencing analysis was performed to detect TTR gene mutations in amyloidosis patients whose results of TTR immunohistochemical staining were positive or equivocal. Clinical presentation was categorized as exclusively cardiac, exclusively neurologic, or mixed phenotype. Of 12 genetic tests performed, seven were positive for TTR mutations. D58A (c.173A>C) was the most common mutation in this study (57%, 4/7). The majority of those patients with hereditary ATTR had the mixed phenotype (86%, 6/7). The patients with D58A mutation had older ages of disease onset (median, 61 years vs. 42 years; P = 0.08), and a higher incidence of gastrointestinal involvement (75% vs. 0%; P = 0.03) than those with other identified TTR mutations. A significant male predominance was also noted in this study (P = 0.01).     

A Propensity Score Matched Comparison of Clinical Outcomes in Atrial Fibrillation Patients Taking Vitamin K Antagonists: Comparing the “Real-World” vs Clinical Trials

Objective

To investigate the incidence and risk of adverse clinical outcomes in a “real-world” cohort of patients with atrial fibrillation (AF) anticoagulated with vitamin K antagonists (VKAs) from the Murcia AF Project in comparison with the warfarin arm of the randomized clinical trial (RCT) AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation).

A novel type of familial transthyretin amyloidosis,ATTR Asn124Ser,with co-localization of κ light chains

A 68-year-old Italian woman who had a clinical history of thyroidectomy in 2002 presented with slowly progressing renal insuffiency and non-nephrotic proteinurea in 2004. A renal biopsy showed the occurrence of amyloid; the thyroid biopsy previously taken also revealed amyloid infiltration. Other amyloid-containing tissues included bone marrow and heart. The plasma cell level in the bone marrow was found to be less than 5% and both serum and urine samples were positive for a monoclonal κ light chain band. DNA analysis unexpectedly revealed the presence of a novel transthyretin (TTR) mutation, ATTR Asn124Ser. Histologically, amyloid deposits in the thyroid had a homogeneous appearance with moderate Congophilia. In immunohistochemistry, a κ light chain antiserum showed positive immunoreactivity with amyloid deposits in the thyroid. Furthermore, a TTR antiserum, anti-TTR50-127, also recognized a number of amyloid deposits stained positive with the κ light chain antiserum. Overall, the κ light chain antiserum reacted with most of the amyloid deposits in the thyroid, whereas TTR immunoreactivity was scarcer, with a scattered appearance. In contrast, only the anti-TTR50-127 antiserum labeled amyloid in the kidney, albeit not all deposits. In this study, we report a patient having a novel TTR variant, ATTR Asn124Ser, with co-localization of κ light chains in the amyloid deposits in the thyroid tissue.     

2007～2008年北京市中药饮片市场质量情况分析

目的分析北京市中药饮片市场的质量情况,提出市场监管重点。方法对2007～2008年北京市中药饮片抽验情况进行统计分析,归纳总结。结果北京市中药饮片一部分品种混乱,有掺伪现象,应作为重点监管对象。结论准确地分析了北京市中药饮片市场的质量状况,归纳总结出混乱的品种。     

使用Access2007管理药品说明书进行模糊查询

目的 建立药品说明书数据库,方便医生、药师、患者查阅.方法 对扫描的药品说明书文件,使用Access2007软件进行管理,创建药品说明书数据库和设置查询.结果 在创建的药品说明书数据库中,输入药品通用名或商品名拼音首字母可快速查询到相应的说明书.结论 利用Access2007建立药品说明书数据库,操作简单,查询方便.