目的探讨动态监测N末端B型钠尿肽前体(NT-proBNP)下应用β受体阻滞剂治疗慢性心力衰竭的临床效果。方法选取82例慢性心力衰竭患者,随机分为研究组和对照组各41例。两组均给予常规治疗,研究组根据NT-proBNP动态监测水平制定美托洛尔用药...目的探讨动态监测N末端B型钠尿肽前体(NT-proBNP)下应用β受体阻滞剂治疗慢性心力衰竭的临床效果。方法选取82例慢性心力衰竭患者,随机分为研究组和对照组各41例。两组均给予常规治疗,研究组根据NT-proBNP动态监测水平制定美托洛尔用药方案,对照组根据患者临床表现及影像学检查结果制定美托洛尔用药方案。两组患者均随访1年,比较治疗前及治疗后1年末的心率变异性,以及心血管性死亡率和复发再住院率。结果治疗后,研究组患者的正常RR间期的标准差(SDNN)、相邻5 min RR间期平均值的标准差(SDANN)均较前升高,而对照组的SDNN、SDANN、相邻RR间期差值的均方根、相邻RR间期>50 ms占全部窦性心搏的比例均较前降低且低于研究组(均P<0.05)。研究组心血管性死亡率及复发再住院率均低于对照组(均P<0.05)。结论对慢性心力衰竭患者进行NT-proBNP动态监测能有效指导β受体阻滞剂的合理使用,改善患者的心脏自主神经功能及预后。展开更多
A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region...A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.展开更多
Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, o...Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.展开更多
Traumatic brain injury （TBI） is the lead- ing cause of mortality and disability among young individuals in our society, and globally the incidence of TBI is rising sharply. Mounting evidence has indicated that apoli...Traumatic brain injury （TBI） is the lead- ing cause of mortality and disability among young individuals in our society, and globally the incidence of TBI is rising sharply. Mounting evidence has indicated that apolipoprotein E （apoE： protein; APOE： gene） genotype influences the outcome after TBI. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of lipid distribution, dysfunction of mitochondrial energy production, oxidative stress and increases intracellular calcium in response to injury. This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid betaprotein precursor metabolism following TBI.展开更多
文摘目的探讨动态监测N末端B型钠尿肽前体(NT-proBNP)下应用β受体阻滞剂治疗慢性心力衰竭的临床效果。方法选取82例慢性心力衰竭患者,随机分为研究组和对照组各41例。两组均给予常规治疗,研究组根据NT-proBNP动态监测水平制定美托洛尔用药方案,对照组根据患者临床表现及影像学检查结果制定美托洛尔用药方案。两组患者均随访1年,比较治疗前及治疗后1年末的心率变异性,以及心血管性死亡率和复发再住院率。结果治疗后,研究组患者的正常RR间期的标准差(SDNN)、相邻5 min RR间期平均值的标准差(SDANN)均较前升高,而对照组的SDNN、SDANN、相邻RR间期差值的均方根、相邻RR间期>50 ms占全部窦性心搏的比例均较前降低且低于研究组(均P<0.05)。研究组心血管性死亡率及复发再住院率均低于对照组(均P<0.05)。结论对慢性心力衰竭患者进行NT-proBNP动态监测能有效指导β受体阻滞剂的合理使用,改善患者的心脏自主神经功能及预后。
基金the Department of Pathophysiology of Hebei Medical University, China for their help
文摘A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.
文摘Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.
文摘Traumatic brain injury （TBI） is the lead- ing cause of mortality and disability among young individuals in our society, and globally the incidence of TBI is rising sharply. Mounting evidence has indicated that apolipoprotein E （apoE： protein; APOE： gene） genotype influences the outcome after TBI. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of lipid distribution, dysfunction of mitochondrial energy production, oxidative stress and increases intracellular calcium in response to injury. This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid betaprotein precursor metabolism following TBI.
