Quantitative magnetic resonance spectroscopy at 3T based on the principle of reciprocity

Quantification of magnetic resonance spectroscopy signals using the phantom replacement method requires an adequate correction of differences between the acquisition of the reference signal in the phantom and the measurement in vivo. Applying the principle of reciprocity, sensitivity differences can be corrected at low field strength by measuring the RF transmitter gain needed to obtain a certain flip angle in the measured volume. However, at higher field strength the transmit sensitivity may vary from the reception sensitivity, which leads to wrongly estimated concentrations. To address this issue, a quantification approach based on the principle of reciprocity for use at 3T is proposed and validated thoroughly. In this approach, the RF transmitter gain is determined automatically using a volume‐selective power optimization and complemented with information from relative reception sensitivity maps derived from contrast‐minimized images to correct differences in transmission and reception sensitivity. In this way, a reliable measure of the local sensitivity was obtained. The proposed method is used to derive in vivo concentrations of brain metabolites and tissue water in two studies with different coil sets in a total of 40 healthy volunteers. Resulting molar concentrations are compared with results using internal water referencing (IWR) and Electric REference To access In vivo Concentrations (ERETIC). With the proposed method, changes in coil loading and regional sensitivity due to B₁ inhomogeneities are successfully corrected, as demonstrated in phantom and in vivo measurements. For the tissue water content, coefficients of variation between 2% and 3.5% were obtained (0.6–1.4% in a single subject). The coefficients of variation of the three major metabolites ranged from 3.4–14.5%. In general, the derived concentrations agree well with values estimated with IWR. Hence, the presented method is a valuable alternative for IWR, without the need for additional hardware such as ERETIC and with potential advantages in diseased tissue.     

Low and High Field Magnetic Resonance for in Vivo Analysis of Seeds

Low field NMR has been successfully used for the evaluation of seed composition and quality, but largely only in crop species. We show here that 1.5T NMR provides a reliable means for analysing the seed lipid fraction present in a wide range of species, where both the seed size and lipid concentration differed by >10 fold. Little use of high field NMR has been made in seed research to date, even though it potentially offers many opportunities for studying seed development, metabolism and storage. Here we demonstrate how 17.5T and 20T NMR can be applied to image seed structure, and analyse lipid and metabolite distribution. We suggest that further technical developments in NMR/MRI will facilitate significant advances in our understanding of seed biology.     

Steady-state nevirapine plasma concentrations are influenced by pregnancy

OBJECTIVES: Optimal plasma concentrations of antiretroviral drugs are required during pregnancy to treat maternal HIV infection and prevent mother-to-child transmission. We investigated the effect of pregnancy on nevirapine (NVP) plasma concentrations. METHODS: We included all HIV-1-infected women for whom NVP plasma concentrations were available as part of routine patient care at two university hospitals. Plasma NVP concentrations were compared for pregnant (n=45) and non-pregnant (n=152) women. Univariate and multivariate linear regression analyses were used to identify and adjust for other confounding factors associated with NVP plasma concentrations. For pregnant women who had a plasma NVP concentration available both during and outside pregnancy, a paired analysis was performed. RESULTS: Steady-state NVP plasma concentrations were lower in pregnant women: 5.2 mg/L (interquartile range 3.9-6.8) vs. 5.8 mg/L (4.3-7.7) (P=0.08). After adjusting for confounders, both pregnancy (regression coefficient=-0.90 mg/L, P=0.046) and African descent (regression coefficient=+1.13 mg/L, P=0.005) influenced NVP concentrations significantly. The paired analysis showed mean concentrations of 4.8 mg/L during pregnancy and 5.8 mg/L outside pregnancy (paired t-test, P=0.073). CONCLUSIONS: Pregnancy has a moderate but significant lowering effect on NVP plasma concentrations. Being of African descent compensates for the lowering effect of pregnancy on NVP concentrations.     

Leukotrienes stimulate pepsinogen secretion from guinea pig gastric chief cells by a nitric oxide-dependent pathway

Leukotrienes (LTs) are involved in many inflammatory conditions including gastric damage induced by nonsteroidal anti-inflammatory drugs. Although LTs stimulate acid secretion, the effect they exert on pepsinogen secretion is unknown. The aim of this study was to investigate whether LTs stimulate pepsinogen secretion by isolated chief cells and to identify the intracellular messengers that mediate this action. Isolated chief cells were incubated with concentrations of LTB₄, LTC₄, LTD₄, or LTE₄ ranging from 0.1 pmol/L to 10 μmol/L, and pepsinogen release, intracellular calcium and inositol(1,4,5)-trisphosphate (IP₃) concentrations were measured. Nitric oxide generation was determined by the amount of citrulline generated during incubation. All four LTs caused a concentration-dependent stimulation of pepsinogen secretion with 50% effective concentration of 0.05-0.1 nmol/L and a dose-dependent increase in cytoplasmic free calcium and IP₃ concentration. The LTB₄ and LTD₄ antagonists caused selective, concentration-dependent inhibition of LTB₄- and LTD₄-induced pepsinogen secretion, calcium mobilization, and IP₃ generation. All four LTs increased NO generation, and the effect was inhibited by LTB₄ and LTD₄ antagonists and an NO synthase inhibitor N^G-monomethyl-l-arginine and reversed by l-arginine. N^G-monomethyl-l-arginine caused a 50%–60% reduction of LT-induced pepsinogen release. Each of the four LTs caused a fivefold increase in 5′-cyclic guanosine monophosphate. LTs are powerful stimulators of pepsinogen secretion in isolated chief cells and act via occupancy of specific cell-surface receptors.     

Fructose-Containing Sugars and Cardiovascular Disease

Cardiovascular disease (CVD) is the single largest cause of mortality in the United States and worldwide. Numerous risk factors have been identified for CVD, including a number of nutritional factors. Recently, attention has been focused on fructose-containing sugars and their putative link to risk factors for CVD. In this review, we focus on recent studies related to sugar consumption and cardiovascular risk factors including lipids, blood pressure, obesity, insulin resistance, diabetes, and the metabolic syndrome. We then examine the scientific basis for competing recommendations for sugar intake. We conclude that although it appears prudent to avoid excessive consumption of fructose-containing sugars, levels within the normal range of human consumption are not uniquely related to CVD risk factors with the exception of triglycerides, which may rise when simple sugars exceed 20% of energy per day, particularly in hypercaloric settings.     

The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat

Summary Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall in plasma insulin and depletion of pancreatic insulin stores were prevented by sucrose supplementation of caffeine-ingesting dams. Offspring of dams fed sucrose alone and control offspring also maintained pancreatic insulin stores and circulating insulin levels over the first 14 days of postnatal life. Pancreases from offspring of caffeine-exposed animals tested in vitro showed enhanced sensitivity of the insulin release process to glucose. This was reflected in the glucose concentration required to elicit half-maximal insulin release (2.4 ± 0.2 mmol/l for caffeine offspring, 2.3 ± 0.2 mmol/l for caffeine with sucrose, 3.8 ± 0.3 mmol/l for sucrose and 4.1 ± 0.3 mmol/l for control offspring, mean ± SEM). In contrast, offspring of sucrose-supplemented (with or without caffeine) dams showed increased sensitivity of the proinsulin biosynthetic process to glucose, whereas offspring of dams ingesting caffeine alone showed no significant enhancement of the biosynthetic process compared with control offspring. Thus enhanced sensitivity of the insulin secretory process to glucose without a change in the sensitivity of the biosynthetic process in the offspring of the caffeine ingesting (nonsucrose supplemented) dams could explain the progressive depletion of pancreatic insulin stores and eventual hypoinsulinaemia seen in this group.     

不同稀释浓度的痰热清注射液对急性上呼吸道感染患儿的疗效与安全性影响

目的:考察不同稀释浓度的痰热清注射液对儿童急性上呼吸道感染(children with acute upper respiratory tract infection,AURTI)的疗效与安全性。方法:抽取2018年1月—12月间收治的采用痰热清注射液治疗的AURTI患儿108例资料,按照痰热清注射液的稀释浓度不同将其分为高浓度组29例、中浓度组40例和低浓度组39例;分析不同痰热清注射液的稀释浓度对各组患儿的临床症状复常时间、总有效率和用药期间不良反应发生率差异。结果:高、中浓度组患儿用药后症状和体征的恢复时间相当(<5 d),但早于低浓度组(<7 d);高、中浓度组用药后的总有效率分别为89.66%和87.50%,经两组间比较其差异无统计学意义(P>0.05),但均显著高于低浓度组(64.10%);中、低浓度组患儿治疗期间不良反应发生率分别为7.50%和5.13%,经两组间比较其差异无统计学意义(P>0.05),但均显著低于高浓度组(31.03%)。结论:痰热清注射液不同稀释浓度对治疗AURTI患儿的疗效和安全性影响较大;适当稀释痰热清注射液的浓度不仅具有良好的临床疗效,而且安全性较高。