Evaluation of the toxicology,anti-lipase,and antioxidant effects of Callistemon citrinus in rats fed with a high fat-fructose diet

ContextCallistemon citrinus Skeels (Myrtaceae) exhibits many biological activities.ObjectiveThis study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD).Materials and methodsFour studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100–4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro.ResultsToxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD₅₀) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC₅₀ of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress.ConclusionsCallistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.     

Impaired Vagal Activity in Long-COVID-19 Patients

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.     

Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches : A workshop report

Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives.     

Developmental origins theory from prematurity to adult disease

Developmental Origins Theory has received little coverage in the nursing literature, even though it has received much attention in other sciences. The theory proposes that prenatal stress provokes adaptive changes in endocrine and metabolic processes that become permanently programmed and impact later adult health. This paper reviews the theory and describes the primary neuroendocrine mechanism of hypothalamic-pituitary-adrenal axis function. Supporting research evidence in preterm infant and adult samples is presented. Through knowledge of the theory and the long-term sequelae for preterm infants, nurses will have a different theoretical perspective and growing evidence to consider in their care for pregnant women and infants.     

纠正千古谬误：中医“脾”在解剖学上对应的脏器非脾非胰而是肝!

作者前已提出中医藏象实质细胞生物学假说,认为中医藏象的实质在于细胞和亚细胞结构。＂五藏＂其实是细胞的＂五脏＂,细胞的＂五脏＂是细胞的五个不同功能系统,可以落实为不同的亚细胞结构,即线粒体——中医之＂脾＂,染色体——中医之＂肾＂,配体-受体-信号转导系统——中医之＂肝＂,细胞膜——中医之＂肺＂,离子通道——中医之＂心＂。在五脏之中,心主行血,肺主呼吸,肾主水液,都有一个解剖学上宏观的实体脏器能与之功能相符。那么,中医之＂脾＂,究竟有无与之相对应的实体脏器？我们说,有。但非脾（spleen）、非胰（pancreas）,是肝（liver）!其理由有五：（1）肝细胞的线粒体数目比所有其他种类细胞都多;（2）中医古医书中有把肝当作＂脾＂的证据;（3）在解剖结构上,肝与消化道的血管的紧密联系;（4）在功能上,肝在消化系统（广义的中医之＂脾胃＂）和物质代谢（＂水谷精微的运化＂）中居于中心地位;中医＂脾＂最主要的也是最根本的功能——＂运化水谷精微＂,不折不扣地是由肝脏来完成。     

胚胎干细胞试验预测胚胎毒性替代方法进展

小鼠胚胎干细胞试验(EST)是通过ECVAM正式验证的胚胎和发育毒性的动物试验替代方法。在新技术的推动下,多项优化的EST方法通过基因转染、利用人来源的干细胞、增加检测通量、组合检测终点、量化检测指标等方式,提高了EST方法预测胚胎毒性的科学相关性和检测效率。在整合测试策略的原则之下,经过大规模化学物质的前验证和标准化试验,新的EST方法可单独或作为组合试验的一部分可以应用于先导药物的研发和化学品的胚胎毒性预测及机制研究。     

自由之旅:高等教育管理学中的人性预设推演

“人性假设”是人文社会学科发展不可回避的理论逻辑前提。管理学与教育学分别极端地反映了人类“工具理性”和“价值理性”的终极诉求,因此尽管各自有诸多的人性假设,但最终却可以概括性地归纳为“效益人”和“圣贤人”假设。高等教育管理学脱胎于管理学与教育学,其人性假设因其总是处于“效益人”和“圣贤人”的两难困境之中,在“工具理性”与“价值理性”之间摇摆徘徊,从而导致高等教育管理的异化,也阻碍了学科自身的发展。高等教育管理目标及其主客体的特殊性说明管理学与教育学中主客二分的思维模式不再适用,只有在“主体间性”的指引下导入“沟通理性”才有可能使高等教育管理走出尴尬处境,而“沟通理性”基础之上的人性预设必然也只能是“自由人”。     

肿瘤中医“耗散病机假说”的建立和固摄法的提出

在反复探索传统中医对肿瘤认识的基础上,结合现代肿瘤理论和非线性平衡理论,从一个新的角度对肿瘤的本质进行分析,提出了中医肿瘤“耗散病机假说”与固摄法。中医肿瘤“耗散病机假说”从更深层次揭示中医肿瘤病机的本质所在,即一方面肿瘤患者自始至终表现正气耗散、正虚失于固摄的过程,另一方面癌毒本身具有易于扩散转移的特性。固摄法正是中医肿瘤“耗散病机假说”的临床具体应用的结果。研究显示:固摄法能有效提高肿瘤患者的生活质量,明显延长肿瘤患者的生存周期,减轻放、化疗的毒副反应。实验研究表明:固摄法能有效提高免疫功能,抑制肿瘤生长,抗肿瘤转移复发,对肿瘤新生血管有明显抑制作用。