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81.
目的 观察高通量血液透析(HFHD)与低通量血液透析(LFHD)的不同模式运用到老年患者维持性血液透析(MHD)中对其血压的影响。方法 选择2015年2月—2017年10月本院治疗的MHD老年患者74例,先为其施LFHD 3个月,再为其辅以3个月的HFHD,3次/周,4 h/次,对比不同透析模式对患者血压的影响。结果 实施HFHD后患者的平均动脉压(MAP)有所降低,在第3 h与第4 h透析后,血压把控优于LFHD(P<0.05)。结论 对于MHD老年患者来说,实施HFHD是优良的透析方法。 相似文献
82.
83.
《Journal of pharmaceutical sciences》2019,108(10):3425-3433
This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation. 相似文献
84.
J.A. Hannam S.J. Mitchell D. Cumin C. Frampton A.F. Merry M.R. Moore C.J. Kruger 《British journal of anaesthesia》2019,122(2):198-205
Background
Etomidate is frequently selected over propofol for induction of anaesthesia because of a putatively favourable haemodynamic profile, but data confirming this perception are limited.Methods
Patients undergoing cardiac surgery were randomised to induction of anaesthesia with propofol or etomidate. Phase I (n=75) was conducted as open-label, whereas Phase II (n=75) was double blind. Mean arterial blood pressure (MAP) and boluses of vasopressor administered after induction were recorded. The primary endpoint was the area under the curve below baseline MAP (MAP-time integral) during the 10 min after induction. Secondary endpoints were the use of vasopressors over the same period, and the effect of blinding on the aforementioned endpoints. Groups were compared using regression models with phase and anaesthetist as factors.Results
The mean difference between etomidate and propofol in the MAP-time integral below baseline was 2244 mm Hg s (95% confidence interval, 581–3906; P=0.009), representing a 34% greater reduction with propofol. Overall, vasopressors were used in 10/75 patients in the etomidate group vs 21/75 in the propofol group (P=0.38), and in 20/74 patients during the blinded phase vs 11/76 during the open-label phase (P=0.31). The interaction between randomisation and phase (open-labelled or blinded) was not significant for either primary (P=0.73) or secondary endpoints (P=0.90).Conclusions
Propofol caused a 34% greater reduction in MAP-time integral from baseline after induction of anaesthesia than etomidate, despite more frequent use of vasopressors with propofol, confirming the superior haemodynamic profile of etomidate in this context. The proportion of patients receiving vasopressors increased slightly, albeit not significantly, in both groups in the blinded phase.Clinical trial registration
Australian and New Zealand Clinical Trials Registry, ACTRN12614000717651. 相似文献85.
《Journal of pharmaceutical sciences》2019,108(7):2500-2504
Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field. 相似文献
86.
《L'Encéphale》2022,48(2):188-195
Depressive disorder is characterized by a polymorphic symptomatology associating emotional, cognitive and behavioral disturbances. One of the most specific symptoms is negative beliefs, called congruent to mood. Despite the importance of these beliefs in the development, the maintenance, and the recurrence of depressive episodes, little is known about the processes underlying the generation of depressive beliefs. In this paper, we detail the link between belief updating mechanisms and the genesis of depressive beliefs. We show how depression alters information processing, generating cognitive immunization when processing positive information, affective updating bias related to the valence of belief and prediction error, and difficultie to disengage from negative information. We suggest that disruption of belief-updating mechanisms forms the basis of belief-mood congruence in depression. 相似文献
87.
Sanne J. H. van Rooij Ryan D. Smith Anaïs F. Stenson Timothy D. Ely Xinyi Yang Nim Tottenham Jennifer S. Stevens Tanja Jovanovic 《Depression and anxiety》2020,37(4):303-312
Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations. 相似文献
88.
《中国现代医生》2020,58(34):60-63
目的 通过检测老年轻度认知障碍(MCI)患者血清瘦素(LEP)、甲状腺激素水平,分析其与局部脑血流量(rCBF)的关系。方法 选择本院收治的128 例老年MCI 患者,另选健康者128 例作为对照组。检测血清LEP、甲状腺激素、大脑各区域rCBF 水平并分析其相关性。结果 老年MCI 组患者左右侧额叶、右侧颞叶、左侧顶叶、左右侧基底节区域脑血流量[(43.81±8.62)mL/(100 g·min)、(43.24±7.93)mL/(100 g·min)、(45.14±6.98)mL/(100 g·min)、(45.86±6.77)mL/(100 g·min)、(67.95±8.52)mL/(100 g·min)、(68.36±8.34)mL/(100 g·min)]低于对照组[(46.39±8.31)mL/(100 g·min)、(46.52±8.56)mL/(100 g·min)、(47.37±7.04)mL/(100 g·min)、(48.25±6.98)mL/(100 g·min)、(70.34±8.96)mL/(100 g·min)、(70.58±8.57)mL/(100 g·min)](P<0.05)。老年MCI 组患者血清LEP、T3、FT3 水平[(4.87±1.56)μg/L、(1.21±0.16)nmol/L、(3.04±0.36)pmol/L]低于对照组[(11.45±3.92)μg/L、(1.68±0.21)nmol/L、(4.82±1.21)pmol/L](P<0.05),TSH 水平为(2.78±0.75)IU/mL,高于对照组的(1.13±0.38)IU/mL(P<0.05)。老年MCI 患者血清LEP 水平与左侧额叶、右侧颞叶、左侧顶叶rCBF 呈正相关(r=0.452、0.537、0.544,P 均<0.05),T3 水平与左侧额叶、右侧颞叶rCBF 呈正相关(r=0.427、0.521,P 均<0.05),FT3 水平与右侧颞叶rCBF 呈正相关(r=0.492,P<0.05),TSH 水平与左侧额叶、右侧颞叶rCBF 呈负相关(r=-0.463、-0.489,P 均<0.05)。结论 老年MCI 患者血清中LEP、T3、FT3 水平降低,TSH 水平升高,且与不同区域rCBF 有相关性,可通过调控脑血管功能影响rCBF 变化水平。 相似文献
89.
90.
黄芪始载于《神农本草经》,有补气升阳、益卫固表,利水消肿,托毒生肌之效。被誉为补气健脾之要药,临床上常用于气虚乏力、脾虚泄泻等疾病,已为医者所熟知。近年来,研究学者围绕其补气、健脾、利水功效机制已有较全面的认识。然陶弘景在《本草经集注》首载黄芪"逐五脏间恶血",表明本品兼有活血作用。目前,对于本品活血作用机制阐释,中医常基于"补气活血""气行血行"理论进行论证,但并不等同于本品无活血作用。通过梳理历代本草文献中对黄芪的记载,发现其活血作用应用广泛。综合传统方剂与现代方剂中有关其活血作用的应用,本品在方中行活血通络、活血利水、活血扶正作用,尤能体现其活血作用。且现代药理学研究在有关瘀血病理指标的分子机制中,黄芪有很好的调控作用,表明黄芪有活血作用,但未深入探究,存在研究价值。该文从历代文献对黄芪活血功效的论述、黄芪活血作用的临床应用及现代药理学研究深入探讨其活血作用机制,以期扩展黄芪的临床应用范围,为临床治疗提供理论指导。 相似文献