Acute haemodynamic effects of i.v. nitrendipine in healthy subjects

Summary The haemodynamic effects of an i.v. infusion of 2 mg nitrendipine have been studied in six healthy volunteers.Nitrendipine significantly decreased the systolic (–8.3%) diastolic (–19.9%) and mean arterial (–11.6%) blood pressures and the peripheral vascular resistance (–57.8%), and significantly increased leg blood flow (+128%).Stroke volume did not change. Due to the increase in heart rate (+28.5%), the cardiac output (2.8.2%) rose significantly. The haemodynamic effects were closely related to the serum nitrendipine concentration. The sigmoidal E_max-model was appropriate to describe the data.Pronounced interindividual differences in the serum nitrendipine concentrations required to elicit 50% of the maximum haemodynamic effect (EC₅₀) were observed. The EC₅₀ for the increase in leg blood flow ranged from 2.9 to 30.9 ng/ml and for the reduction in peripheral vascular resistance from 2.1 to 25.7 ng/ml. Interindividual differences in EC₅₀ values were less pronounced if based on unbound serum nitrendipine levels.The fraction of nitrendipine not bound to serum proteins showed a three-fold difference between subjects, with free fractions ranging from 0.011 to 0.036. The unbound EC₅₀ values for the increase in leg blood flow varied between 0.06 and 0.44 ng/ml and for the reduction in peripheral vascular resistance from 0.07 to 0.35 ng/ml.Based on the serum concentrations associated with comparable haemodynamic effects nitrendipine was at least three-times more potent than nifedipine.     

乳熟期鲜食玉米穗不同部位碳水化合物的变化

对乳熟期鲜食玉米穗不同部位碳水化合物的变化研究表明，籽粒中可溶性总糖（TSC）质量分数为先增加后降低，蔗糖（SUC）和TSC的变化趋势相似，淀粉质量分数逐渐增加，可溶性酸性蔗糖转化酶的活性先增加后降低．穗轴中SUC及TSC质量分数在授粉后任何时期总是高于籽粒，淀粉质量分数远低于籽粒．苞皮中TSC与SUC质量分数缓慢减少，在籽粒灌浆初期积累有大量的TSC，为籽粒迅速灌浆做出了贡献，淀粉质量分数远低于穗轴．鲜食玉米采收后应低温放置或及时加工，以抑制糖快速转化为淀粉，防止鲜食玉米品质下降．     

Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II: Muscle,liver, kidney

Absolute metabolite concentrations were assessed in the muscle, the liver, and the kidney of healthy human volunteers by ³¹P MRS. Fully relaxed in vivo spectra were acquired with a surface coil and were localized with an adiabatic lSlS pulse sequence. The spectra were quantified with a subsequent measurement of a calibration phantom and were processed iteratively in the time domain. The following mean metabolite concentrations (mmollliter) were measured in the resting male calf muscle (n = 9), in the fasting liver (n = 12), and in the orthiotopic kidney (n= 5): [PME] = 2.0 ± 0.6, 3.8 ± 0.7, and 2.6 ± 0.9, [Pi] = 2.9 ± 0.3, 1.8 ± 0.3, and 1.6 ± 0.4, [PDE] = 3.8 ± 0.8, 9.7 ± 1.5, and 4.9 ± 1.1, [PCr] = 22.0 ± 1.2, 0, and 0, [NTP] = 5.7 ± 0.4, 2.9 ± 0.4, and 2.0 ± 0.3, respectively. Several interesting findings are to be emphasized: The concentrations of Pi, PCr, and NTP were 20% lower in the muscle of women than of men. In addition, the pH, was significantly lower in female muscle (6.99 ± 0.03) than in male muscle (7.05 ± 0.03). The pH, in the liver (7.12 ± 0.09) and in the kidney (7.09 ± 0.08) were higher than in the muscle of both genders. The free magnesium concentration (mmollliter) was higher in the lliver (1.40 ± 0.64) than in the kidney (0.79 ± 0.39) and in the muscle (0.52 ± 0.10).     

重复大量摄入蔗糖与麦芽糖对健康成人胰岛功能的影响

<正>随着经济水平的提高,生活方式的西化,含有大量精制糖的西点,成为年轻人能量摄入的重要组成部分。据报道,与全麦食品相比,摄入大量含精制糖的食品可引起低血糖[1]。短暂的低血糖可引起明显的脑功能紊乱和认知障碍,丧失驾驶能力[2]。然而,是否短时间内摄入大量糖分引起胰岛素分泌增加,从而导致低血糖尚未得到证实。蔗糖和麦芽糖均为双糖,经常被用为食品中的调味料或添加剂。本实验研究比较短时间内重复大量摄入蔗糖或麦芽糖对胰岛素分泌的影响。     

Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations

Natriuretic peptide [NP; B‐type NP (BNP), N‐terminal proBNP (NT‐proBNP), and midregional proANP (MR‐proANP)] concentrations are quantitative plasma biomarkers for the presence and severity of haemodynamic cardiac stress and heart failure (HF). End‐diastolic wall stress, intracardiac filling pressures, and intracardiac volumes seem to be the dominant triggers. This paper details the most important indications for NPs and highlights 11 key principles underlying their clinical use shown below.

1. NPs should always be used in conjunction with all other clinical information.
2. NPs are reasonable surrogates for intracardiac volumes and filling pressures.
3. NPs should be measured in all patients presenting with symptoms suggestive of HF such as dyspnoea and/or fatigue, as their use facilitates the early diagnosis and risk stratification of HF.
4. NPs have very high diagnostic accuracy in discriminating HF from other causes of dyspnoea: the higher the NP, the higher the likelihood that dyspnoea is caused by HF.
5. Optimal NP cut‐off concentrations for the diagnosis of acute HF (very high filling pressures) in patients presenting to the emergency department with acute dyspnoea are higher compared with those used in the diagnosis of chronic HF in patients with dyspnoea on exertion (mild increase in filling pressures at rest).
6. Obese patients have lower NP concentrations, mandating the use of lower cut‐off concentrations (about 50% lower).
7. In stable HF patients, but also in patients with other cardiac disorders such as myocardial infarction, valvular heart disease, atrial fibrillation or pulmonary embolism, NP concentrations have high prognostic accuracy for death and HF hospitalization.
8. Screening with NPs for the early detection of relevant cardiac disease including left ventricular systolic dysfunction in patients with cardiovascular risk factors may help to identify patients at increased risk, therefore allowing targeted preventive measures to prevent HF.
9. BNP, NT‐proBNP and MR‐proANP have comparable diagnostic and prognostic accuracy.
10. In patients with shock, NPs cannot be used to identify cause (e.g. cardiogenic vs. septic shock), but remain prognostic.
11. NPs cannot identify the underlying cause of HF and, therefore, if elevated, must always be used in conjunction with cardiac imaging.

     

Melatonin regulates carbohydrate metabolism and defenses against Pseudomonas syringae pv. tomato DC3000 infection in Arabidopsis thaliana

Melatonin has been reported to promote plant growth and development. Our experiments with Arabidopsis thaliana showed that exogenous applications of this molecule mediated invertase inhibitor (C/VIF)‐regulated invertase activity and enhanced sucrose metabolism. Hexoses were accumulated in response to elevated activities by cell wall invertase (CWI) and vacuolar invertase (VI). Analyses of sugar metabolism‐related genes revealed differential expression during plant development that was modulated by melatonin. In particular, C/VIF1 and C/VIF2 were strongly down‐regulated by exogenous feeding. We also found the elevated CWI activity in melatonin‐treated Arabidopsis improved the factors (cellulose, xylose, and galactose) for cell wall reinforcement and callose deposition during Pseudomonas syringae pv. tomato DC3000 infection, therefore, partially induced the pathogen resistance. However, CWI did not involve in salicylic acid (SA)‐regulated defense pathway. Taken together, this study reveals that melatonin plays an important role in invertase‐related carbohydrate metabolism, plant growth, and pathogen defense.     

Accurate determination of brain metabolite concentrations using ERETIC as external reference

Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For ¹H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil‐loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B₁ inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field ( ) differences are minimized with a volume‐selective power optimization, whereas reception sensitivity changes are corrected using contrast‐minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B₁ correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite concentration, with potential advantages compared with internal water referencing in diseased tissue.     

Variants of self-assembling peptide,KLD-12 that show both rapid fracture healing and antimicrobial properties

KLD-12 (KLD) is a 12-residue self-assembling peptide that can adopt nano-structures and is known for its tissue-engineering properties. Our objective was to introduce antimicrobial attribute to KLD which would help in preventing secondary infection associated with external application of such tissue engineering materials. Considering the net charge of KLD-12, varying number of cationic arginine residues were added to its N-terminus. KLD variants showed appreciable bactericidal properties without any significant increase in cytotoxicity against tested mammalian cells. Further, these variants adopted β-sheet structures and self-assembled into nano-structures comparable to that of KLD. Interestingly, the KLD variants with two (KLD-2R) and three (KLD-3R) arginine residues added to its N-terminus showed significant osteogenic effect which was comparable or better than the original peptide as evident from the alkaline phosphatase activity assay, mineralized nodule formation and expression of different osteogenic genes. Particularly, application of KLD-2R in rats to the site of a drill-hole (0.8 mm diameter) that was created in the femur metaphysis displayed significantly higher bone regeneration compared to that of KLD. The results demonstrate a simple way to improve biological property of a self-assembling peptide with tissue engineering property.     

中成药DNA提取技术优化及其在人参类制剂分子鉴定中的应用

目的 建立并完善从中成药及保健品中提取DNA的有效方法,并在人参类制剂中进行验证。方法 使用中成药和保健品中常用的辅料(如淀粉、蔗糖、葡萄糖等)模拟CTAB法提取DNA过程,用以筛选影响提取DNA效率的因素;使用甲醇作为沉淀试剂优化传统的CTAB法,并使用MAS-PCR方法对市场上人参类中成药及保健品进行分子鉴定,以验证优化的技术。结果 中成药及保健品中的淀粉(包括药源性淀粉和辅料添加的淀粉)通过CTAB反应后生成极性较大的复合物,其与70%乙醇不能互溶,而且在碱性条件下对DNA有强烈的溶解作用,从而影响了CTAB法提取DNA的提取效率;利用甲醇作为沉淀试剂能够有效去除CTAB裂解过程中产生的高极性复合物的影响,70%甲醇-醋酸钠溶液能够有效提取中成药及保健品的DNA;利用优化的DNA提取方法和MAS-PCR法实现了11种市售人参类制剂的快速分子鉴定,结果显示8种与商品描述一致、1种有掺伪情况、2种为伪品。结论 使用甲醇作为沉淀试剂优化传统的CTAB法,可以较好地克服中药制剂中淀粉对DNA提取的不利影响,可以有效地实现基于DNA的中药制剂分子鉴定。