Premium rates based on genetic studies: How reliable are they?

Underwriting the risk of rare disorders in long-term insurance often relies on rates of onset estimated from quite small epidemiological studies. These estimates can have considerable sampling uncertainty and any function based upon them, such as a premium rate, is also an estimate subject to uncertainty. This is particularly relevant in the case of genetic disorders, because the acceptable use of genetic information may depend on establishing its reliability as a measure of risk. The sampling distribution of a premium rate is hard to estimate without access to the original data, which is rarely possible. From two studies of adult polycystic kidney disease (APKD) we obtain, not the original data, but the cases and exposures used for Kaplan-Meier estimates of the survival probability. We use three resampling methods with these data, namely: (a) the standard bootstrap; (b) the weird bootstrap; and (c) simulation of censored random lifetimes. Rates of onset were obtained from each simulated sample using kernel-smoothed Nelson-Aalen estimates, hence critical illness insurance premium rates for a mutation carrier or a member of an affected family. From 10,000 such samples we estimate the sampling distributions of the premium rates, finding considerable uncertainty. Very careful consideration should be given before using small-sample epidemiological data to deal with insurance problems.     

A Reevaluation of the Critical Membrane Potential of the Effective Refractory Period in Guinea Pig Ventricular Fibres

The traditional critical membrane potential (CMP), -55—-60mV, which corresponds to effective refractory period (ERP), was anew investigated in guinea pig ventricular muscle fibres. The electrical and contractile responses to the stimulus during repolarization of action potential (AP), particularly from+10 to -60 mV, were observed. One third of 35 tested cells displayed testing action potential (TAP) and local response at≥-54 mV when they were stimulated by testing pulses in 37℃ normal Tyrode's solution. Potential level of TAP which occurred earliest was at -30 mV and that of local response which appeared earliest was at 0 mV during repolarization among 95 systematic tests. Most of the TAPs belonged to the slow response potential type. The ratio of TAP evoked at ≥-54 mV initial membrane potential (IMP) was as high as 86% when the experiment was carried out in 37℃ 1.5 mmol KC1/L Tyrode's solution. In view of distribution of IMPs of TAPs, the CMP of ERP in guinea pig ventricular muscle fibres was more     

中医补肾壮骨理论与微量元素

探讨了中医理论与微量元素的关系，重点介绍了补肾药和肾主骨主生长发育的理论与微量元素的关系。为中医随证配伍选药提供了理论基础。     

中毒样品中灭鼠药的分析鉴定与人工炭肾治疗效果浅评

1991年7月某单位发生集体食物中毒,78人发病。当时迫切需要鉴定出毒物,以便对这起中毒病人进行抢救治疗。本文建立了未见文献报道的血样,炭肾中痕量“四二四”的分离提取方法和GC-MS分析鉴定方法,在中毒样品中鉴定出剧毒灭鼠药“四二四”。根据治疗用的人工炭肾及治疗后病人血样的鉴定结果,对用人工炭肾透析治疗“四二四”中毒的疗效进行了评价。     

High‐performance liquid chromatographic method for the quantification of Mitragyna inermis alkaloids in order to perform pharmacokinetic studies

In Africa, Mitragyna inermis (Willd.) O. Kuntze (Rubiaceae) is commonly used in traditional medicine to treat malaria. Antimalarial activity is mostly due to the hydromethanolic extract of M. inermis leaves and especially to the main alkaloids, uncarine D and isorhynchophilline. In the present study, we describe for the first time an HPLC method for the simultaneous quantification of uncarine D and isorhynchophylline in biological matrices. SPE was used to extract the components and the internal standard naphthalene from human and pig plasma samples. Chromatographic separation was performed on a C‐18 reversed column at a flow rate of 1 mL/min, using methanol–phosphate buffer (10:90, pH 7), as a mobile phase. Good linearity was observed over the concentration ranges of 0.0662–3.31 μg/mL for uncarine D and 0.0476–2.38 μg/mL for isorynchophylline. The precision was less than 12% and the accuracy was from 86 to 107% without any discrepancy between the two species. Uncarine D and isorhynchophylline recoveries were over 80%. These results allowed the quantification of both uncarine D and isorhynchophylline in pig plasma after intravenous administration of M. inermis extract.     

The determination of β-agonist residues in bovine tissues using liquid chromatography–tandem mass spectrometry

We aimed to develop a rapid, simple and reproducible method based on LC–tandem mass spectrometry (LC–MS/MS) to analyze β-agonist residues (clenbuterol, zilpaterol, ractopamine and isoxsuprine) in bovine tissues. The method was validated in accordance with the European Council Decision 2002/657/EC. The samples were homogenized, and then 10 mL of an acetate buffer was added to a 5-g sample. The sample was then centrifuged at 12,000 rpm and filtered. Sodium hydroxide (2 m ) was added to adjust pH of the sample that was centrifuged again. The extract was filtered through a solid-phase extraction column. The residue was re-dissolved in 250 μL acetonitrile and then subjected to LC–MS/MS. The separation was done on a C₁₈ column. The mobile phase consisted of 0.1% formic acid in deionized water and 0.1% formic acid in methanol. The mean recoveries of β-agonists were in the range of 84.3%–119.1% with relative standard deviations (%RSDs) of 0.683%–4.05%. Decision limits and detection capabilities of the analytes ranged from 0.0960 to 4.9349 μg/kg and from 0.0983 to 5.0715, respectively. This method was used to detect four β-agonists in 100 bovine muscle, 100 liver and 100 kidney tissues from a slaughterhouse. No residue was found above the maximum residue limit level.     

Simultaneous determination of spinosad,temephos, and piperonyl butoxide in animal‐derived foods using LC–MS/MS

Pesticides, which are used as plant protection products, can enter the food chain, and exposure to these xenobiotics can cause a wide array of health problems in humans. Therefore, the objective of the present study was to develop an analytical method for the simultaneous determination of residual spinosad (sum of spinosyn A and D), temephos and piperonyl butoxide in porcine muscle, egg, milk, eel, flatfish and shrimp (sampling period: February to June 2018) using liquid chromatography–triple quadrupole tandem mass spectrometry (LC–MS/MS). The target analytes were extracted with a combination of acidified acetonitrile and ethyl acetate and subsequently purified with original QuEChERS kits (composed of magnesium sulfate and sodium chloride) as well as n‐hexane. All analytes were separated on a reversed‐phase analytical column using a mobile phase of (A) 0.1% formic acid containing 10 mm ammonium formate in distilled water and (B) methanol. Good linearity (R² ≥ 0.980) was achieved over the tested concentration range (3.5–35 μg/kg for spinosyn A; 1.5–15 μg/kg for spinosyn D; 5–50 μg/kg for temephos and piperonyl butoxide) in matrix‐matched standard calibrations. Fortified samples at three spiking levels yielded recoveries in the range of 71–105% with relative standard deviations ≤9.2%. The applicability of the method was evaluated via evaluating samples collected from a large wholesale market located in Seoul, and none of the samples contained any of the target analytes. In conclusion, the current approach is simple, efficient and reliable and can successfully determine the residual levels of spinosad, temephos and piperonyl butoxide in complex animal‐derived food products.     

Ga(III) complex with morin for kidney cancer cell labelling

The formation of a complex between Ga(III) and morin (3,5,7,2′,4′‐pentahydroxyflavone) was studied. UV–visible, infrared and mass spectroscopies were used to characterize the complex. The stoichiometric ratio for the reaction between metal ion and flavonoid was determined using the methods of Yoe–Jones and Job, which confirmed that a 1:1 Ga–morin complex was formed (estimated binding constant = 2.31 × 10⁴ l mol⁻¹). It was found that the coordination to Ga(III) occurs through the carbonyl oxygen atom and the 3‐OH group of the morin molecule. According to developed conditions, complexation reaction with ⁶⁸Ga was performed and the complex was used to label kidney cancer cells (CAKI‐1, CAKI‐2, ACHN and 786‐O). The knowledge gained from this study should be useful for the development of new radiopharmaceuticals for diagnostic purposes containing ⁶⁸Ga.     

肾小球滤过率活体实时监测荧光示踪剂的研究进展

急性肾损伤是一种临床常见的急性疾病. 通过外源性的荧光示踪剂对肾小球滤过率进行非侵入性的实时监测, 对于及时了解易患病人的肾脏功能具有重要的临床价值和应用前景. 本文综合评述了用于活体检测肾小球滤过率的外源性荧光示踪剂的近期研究进展, 重点介绍了荧光示踪剂的设计策略及其活体成像应用效果, 并对相应检测装置的发展进行了阐述, 同时对该领域的挑战与发展前景进行了展望.