Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensit...Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.展开更多
由于电离层电子密度随时间变化,且空间分布不均匀,对不同频段的无线电波产生延缓和折射,因此电离层电子密度变化是影响短波通信、卫星通信、全球导航卫星系统和其他空间通信质量的一个主要因素,本文对全球电离层电子密度(Number of elec...由于电离层电子密度随时间变化,且空间分布不均匀,对不同频段的无线电波产生延缓和折射,因此电离层电子密度变化是影响短波通信、卫星通信、全球导航卫星系统和其他空间通信质量的一个主要因素,本文对全球电离层电子密度(Number of electron,Ne)的预测工作对短波通信设备三维射线实时追踪定位提供必要条件。本文采用国际电离层参考模型提供的2016年电离层Ne数据,根据数据的三维空间时间序列特征,搭建了自编码器和卷积长短期记忆(Convolutional Long Short-Term Memory Network,Conv LSTM)网络组成的网络结构,在不引入地球自转周期之外任何先验知识的条件下,对Ne数据进行深度学习并实现预测,首先通过实验对比了SGD、Adagrad、Adadelta、Adam、Adamax和Nadam六种优化算法的性能,又对比了三种预测策略的均方根误差(Root Mean Square Error, RMSE),1h-to-1h预测策略的全球平均RMSE为1.0 NEU(最大值的0.4%),1h-to-24h和24h-to-24h预测策略的全球平均RMSE为6.3 NEU(2.6%)。由实验结果得出以下结论,一是Nadam优化算法更适合电离层Ne的深度学习,二是1h预测策略的性能与之前类似的电离层TEC预测工作(RMSE高于1.5 TECU,最大值的1%)相比有竞争力,但预测时间太短且对数据的实时性要求较高,三是两种24h预测策略虽能实现长期预测但性能不理想,要实现三维空间时间序列的长期高精度预测需要进一步改善神经网络、模型结构和预测策略。展开更多
BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorde...BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE： This study was designed to observe the effects of electro-acupuncture, at the ＂Sanyinjiao＂ point （SP 6）, on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN： A randomized controlled animal experiment. SETTING： This study was performed in the Laboratory of Acupuncture, Electro-acupuncture ＆ Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS： A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China （1985）. Experimental reagents and equipment used were as follows： morphine hydrochloride （Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China）, norepinephrine （Sigma Chemical Company, USA）, fluorospectrophotometer （RF-510, Shimadzu Corporation, Japan）, Han electro-acupuncture apparatus （WQ 1002, No. zun （91）-227270-588, Beijing Anlong Photoelectricity-Technique Company, China）, and T-maze （self-made）. METHODS： A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group： blank control, T-maze, model, model ＋ electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal： the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively （initially 2.95 mg/kg, then increased day by day, as described below）. Interventions： In the model ＋ electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral ＂Sanyinjiao＂ （SP6） points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model ＋ electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES： Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS： A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model ＋ electro-acupuncture groups, （P 〈 0.05-0.01）. Brain norepinephrine content was similar between the model ＋ electro-acupuncture and the blank control groups （P 〉 0.05）. There was no significant difference in blood lactic acid content among the groups （P 〉 0.05）. CONCLUSION： Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.展开更多
Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception...Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.展开更多
The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in...The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.展开更多
With its complex nonlinear dynamic behavior,the tristable system has shown excellent performance in areas such as energy harvesting and vibration suppression,and has attracted a lot of attention.In this paper,an asymm...With its complex nonlinear dynamic behavior,the tristable system has shown excellent performance in areas such as energy harvesting and vibration suppression,and has attracted a lot of attention.In this paper,an asymmetric tristable design is proposed to improve the vibration suppression efficiency of nonlinear energy sinks(NESs)for the first time.The proposed asymmetric tristable NES(ATNES)is composed of a pair of oblique springs and a vertical spring.Then,the three stable states,symmetric and asymmetric,can be achieved by the adjustment of the distance and stiffness asymmetry of the oblique springs.The governing equations of a linear oscillator(LO)coupled with the ATNES are derived.The approximate analytical solution to the coupled system is obtained by the harmonic balance method(HBM)and verified numerically.The vibration suppression efficiency of three types of ATNES is compared.The results show that the asymmetric design can improve the efficiency of vibration reduction through comparing the chaotic motion of the NES oscillator between asymmetric steady states.In addition,compared with the symmetrical tristable NES(TNES),the ATNES can effectively control smaller structural vibrations.In other words,the ATNES can effectively solve the threshold problem of TNES failure to weak excitation.Therefore,this paper reveals the vibration reduction mechanism of the ATNES,and provides a pathway to expand the effective excitation amplitude range of the NES.展开更多
The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE ...The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.展开更多
Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been ...Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.展开更多
The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been d...The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been demonstrated to improve tissue oxygenation, microcirculation, renal function and overall outcome of the patient in some studies and literature on actual hemodynamic goals is scarce. AIM: To study the influence of two MAP on tissue oxygenation and perfusion parameters in patients of septic shock on norepinephrine infusion. SUBJECT AND MATERIALS: Forty adult patients with the diagnosis of septic shock were enrolled. In all patients norepinephrine was titrated to first stabilize the MAP at 65 ± 5 mmHg (Set I), followed by MAP of 85 ± 5 mmHg (Set II). Heart rate (HR), Central venous oxygen saturation (SCVO2), Transcutaneous partial pressure of oxygen (PtcO2) by TCM 400/TINA (using miniature Clark electrode), Arterial partial pressure of oxygen(PaO2), PtO2/PaO2 ratio, Urine output and Serum Base deficit were recorded in each Set after 2 hrs of stabilization. RESULTS: There was a significant increase in transcutaneous partial pressure of oxygen PtcO2 (p tO2/PaO2 (p < 0.0001), ScvO2 (p < 0.0001), urine output (p < 0.006) on increasing the MAP from 65mmHg to 85mmHg. Serum base deficit also improved (p < 0.0001). CONCLUSION: Higher MAP with norepinephrine is associated with better perfusion, oxygenation parameters in patients with established septic shock. These findings suggest that there is improvement in tissue oxygenation parameters using escalating doses of norepinephrine to achieve higher MAP without inherent adverse展开更多
BACKGROUND： It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells （BMSCs） can in vitro induce and differentiate into t...BACKGROUND： It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells （BMSCs） can in vitro induce and differentiate into the cells possessing the properties of nerve cells. But the functions of BMSCs-derived neural stem cells（NSCs） and the differentiated neuron-like cells are still unclear. OBJECTIVE： To observe whether bone marrow-derived NSCs can secrete norepinephrine （NE） under the condition of in vitro culture, induce and differentiation, and analyze the biochemical properties of BMSCs-derived NSCs. DESIGN： A non-randomized and controlled experimental observation SETTING ： Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University MATERIALS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5- month-old healthy New Zealand white rabbits. METHODS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5 month-old healthy New Zealand white rabbits. BMSCs of rabbits were isolated and performed in vitro culture, induce and differentiation with culture medium of NSCs and differentiation-inducing factor, then identified with immunocytochemical method. Experimental grouping： ①Negative control group： L-02 hepatic cell and RPMI1640 culture medium were used. ② Background culture group： Only culture medium of NSCs as culture solution was added into BMSCs to perform culture, and 0.1 volume fraction of imported fetal bovine serum was supplemented 72 hours later. ③Differentiation inducing factor group： After culture for 72 hours, retinoic acid and glial cell line-derived neurotrophic factors were added in the culture medium of BMSCs and NSCs as corresponding inducing factors. The level of NE in each group was detected on the day of culture and 5, 7, 14 and 20 days after culture with high performance liquid chromatography （HPLC）. The procedure was conducted 3 times in each group.Standard working curve was made according to the corresponding relationship of NE concentration and peak area. The concentration of NE every 1×10^7 cells was calculated according to standard curve and cell counting. MAIN OUTCOME MEASURES ： The level of NE of cultured cells was detected with HPLC; immunocytochemistrical identification of Nestin and neuron specific nuclear protein was performed. RESULTS： ① On the 14^th day after cell culture, BMSCs turned into magnus and round cells which presented Nestin-positive antigen, then changed into neuron-like cells with long processus and presented neuron specific nuclear protein -positive antigen at the 20^th day following culture. ② The ratio of NE concentration and peak area has good linear relationship, and regression equation was Y=1.168 36＋0.000 272 8X,r=-0.998 4. Coefficient variation （CV） was 〈 5% and the recovery rate was 92.39%（ Y referred to concentration and X was peak area）.③NE was well detached within 10 minutes under the condition of this experiment. ④ NE was detected in NSCs and their culture mediums, which were cultured for 7, 14 and 20 days respectively, but no NE in BMSCs, NSCs-free culture medium and L-02 hepatic cell which were as negative control under the HPLC examination. Analysis of variance showed that the level of NE gradually increased following the elongation of culture time （P 〈 0.01 ）. No significant difference in the level of NE existed at the same time between differentiation inducing factor group and basic culture group（P 〉 0.05）. CONCLUSION ： BMSCs of rabbits can proliferate in vitro and express Nestin antigen; They can differentiate into neuron-like cells, express specific neucleoprotein of mature neurons, synthesize and secrete NE as a kind of neurotransmitter.展开更多
Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the additio...Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.展开更多
The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(N...The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(NE).After synapse transmissionwas blocked by perfusion of artificial cerebrospinal fluid(ACSF)with low calcium andhigh magnesium,5 in 8 neurons were still sensitive to both 5-HT and NE.On the otherhand,3 in 5 neurons responding only to 5-HT or NA were sensitive to both 5-HT andNE after the synapse transmission blockage.In some neurons which exhibited excitatoryor inhibitory responses to 5-HT or NE alone,the responses were inversed when perfusedwith 5-HT and NE in combination.These results suggest that there may exist aninhibitory interaction between 5-HT receptors and α-adrenoceptors in NTS and that most5-HT and α-adrenoceptors coexist in the same NTS neurons.展开更多
The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group wer...The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.展开更多
The post-collisional Cenozoic basic volcanic rocks in NE Turkey show temporal variations in whole-rock lithophile element and highly siderophile element(HSE)systematics that are mainly associated with the nature of su...The post-collisional Cenozoic basic volcanic rocks in NE Turkey show temporal variations in whole-rock lithophile element and highly siderophile element(HSE)systematics that are mainly associated with the nature of sub-continental lithospheric mantle(SCLM)sources and parental melt generation.So far,the traditional whole-rock lithophile geochemical data of these basic volcanic rocks have provided important constraints on the nature of SCLM sources.Integrated lithophile element and HSE geochemical data of these basic volcanic rocks also reveal the heterogeneity of the SCLM source,which is principally related to variable metasomatism resulting from previous subduction(s)and post-collisional mantle-crust interactions in an extensional setting.Lithophile element geochemical features suggest that the parental magmas have derived from metasomatized spinel-to garnet-bearing SCLM sources for Eocene and Miocene basic volcanic rocks with subduction signatures whereas originated from spinel-to garnet-bearing SCLM sources for Mio-Pliocene and Plio-Quaternary basaltic volcanic rocks without the subduction signature.Lithophile element and HSE geo-chemistry also reveal that Eocene and Miocene basic vol-canic rocks were affected by more pronounced crustal contamination than the basaltic volcanic rocks of Mio-Pliocene and Quaternary.Furthermore,the integrated lithophile element and HSE compositions of these basic volcanic rocks,together with the regional asymmetric lithospheric delamination model,reveal that the compositional variation(especially due to metasomatism)was significant temporally in the heterogeneity of the SCLM sources from which parental magmas formed during the Cenozoic era.展开更多
This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of ...This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of peripheral sympathetic nervous system.展开更多
文摘Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.
文摘由于电离层电子密度随时间变化,且空间分布不均匀,对不同频段的无线电波产生延缓和折射,因此电离层电子密度变化是影响短波通信、卫星通信、全球导航卫星系统和其他空间通信质量的一个主要因素,本文对全球电离层电子密度(Number of electron,Ne)的预测工作对短波通信设备三维射线实时追踪定位提供必要条件。本文采用国际电离层参考模型提供的2016年电离层Ne数据,根据数据的三维空间时间序列特征,搭建了自编码器和卷积长短期记忆(Convolutional Long Short-Term Memory Network,Conv LSTM)网络组成的网络结构,在不引入地球自转周期之外任何先验知识的条件下,对Ne数据进行深度学习并实现预测,首先通过实验对比了SGD、Adagrad、Adadelta、Adam、Adamax和Nadam六种优化算法的性能,又对比了三种预测策略的均方根误差(Root Mean Square Error, RMSE),1h-to-1h预测策略的全球平均RMSE为1.0 NEU(最大值的0.4%),1h-to-24h和24h-to-24h预测策略的全球平均RMSE为6.3 NEU(2.6%)。由实验结果得出以下结论,一是Nadam优化算法更适合电离层Ne的深度学习,二是1h预测策略的性能与之前类似的电离层TEC预测工作(RMSE高于1.5 TECU,最大值的1%)相比有竞争力,但预测时间太短且对数据的实时性要求较高,三是两种24h预测策略虽能实现长期预测但性能不理想,要实现三维空间时间序列的长期高精度预测需要进一步改善神经网络、模型结构和预测策略。
基金the Grant from Administration of Traditional Chinese Medicine of Sichuan Province, No. 2000-48
文摘BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE： This study was designed to observe the effects of electro-acupuncture, at the ＂Sanyinjiao＂ point （SP 6）, on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN： A randomized controlled animal experiment. SETTING： This study was performed in the Laboratory of Acupuncture, Electro-acupuncture ＆ Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS： A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China （1985）. Experimental reagents and equipment used were as follows： morphine hydrochloride （Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China）, norepinephrine （Sigma Chemical Company, USA）, fluorospectrophotometer （RF-510, Shimadzu Corporation, Japan）, Han electro-acupuncture apparatus （WQ 1002, No. zun （91）-227270-588, Beijing Anlong Photoelectricity-Technique Company, China）, and T-maze （self-made）. METHODS： A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group： blank control, T-maze, model, model ＋ electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal： the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively （initially 2.95 mg/kg, then increased day by day, as described below）. Interventions： In the model ＋ electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral ＂Sanyinjiao＂ （SP6） points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model ＋ electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES： Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS： A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model ＋ electro-acupuncture groups, （P 〈 0.05-0.01）. Brain norepinephrine content was similar between the model ＋ electro-acupuncture and the blank control groups （P 〉 0.05）. There was no significant difference in blood lactic acid content among the groups （P 〉 0.05）. CONCLUSION： Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.
文摘Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.
基金supported by the National Natural Science Foundation of China,No. 30770770,30971054,and81171290Science Foundation for the Youth of Shanxi,No.2011021036-1
文摘The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.
基金Project supported by the National Science Fund for Distinguished Young Scholars of China(No.12025204)the National Natural Science Foundation of China(No.12202038)。
文摘With its complex nonlinear dynamic behavior,the tristable system has shown excellent performance in areas such as energy harvesting and vibration suppression,and has attracted a lot of attention.In this paper,an asymmetric tristable design is proposed to improve the vibration suppression efficiency of nonlinear energy sinks(NESs)for the first time.The proposed asymmetric tristable NES(ATNES)is composed of a pair of oblique springs and a vertical spring.Then,the three stable states,symmetric and asymmetric,can be achieved by the adjustment of the distance and stiffness asymmetry of the oblique springs.The governing equations of a linear oscillator(LO)coupled with the ATNES are derived.The approximate analytical solution to the coupled system is obtained by the harmonic balance method(HBM)and verified numerically.The vibration suppression efficiency of three types of ATNES is compared.The results show that the asymmetric design can improve the efficiency of vibration reduction through comparing the chaotic motion of the NES oscillator between asymmetric steady states.In addition,compared with the symmetrical tristable NES(TNES),the ATNES can effectively control smaller structural vibrations.In other words,the ATNES can effectively solve the threshold problem of TNES failure to weak excitation.Therefore,this paper reveals the vibration reduction mechanism of the ATNES,and provides a pathway to expand the effective excitation amplitude range of the NES.
文摘The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.
文摘Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.
文摘The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been demonstrated to improve tissue oxygenation, microcirculation, renal function and overall outcome of the patient in some studies and literature on actual hemodynamic goals is scarce. AIM: To study the influence of two MAP on tissue oxygenation and perfusion parameters in patients of septic shock on norepinephrine infusion. SUBJECT AND MATERIALS: Forty adult patients with the diagnosis of septic shock were enrolled. In all patients norepinephrine was titrated to first stabilize the MAP at 65 ± 5 mmHg (Set I), followed by MAP of 85 ± 5 mmHg (Set II). Heart rate (HR), Central venous oxygen saturation (SCVO2), Transcutaneous partial pressure of oxygen (PtcO2) by TCM 400/TINA (using miniature Clark electrode), Arterial partial pressure of oxygen(PaO2), PtO2/PaO2 ratio, Urine output and Serum Base deficit were recorded in each Set after 2 hrs of stabilization. RESULTS: There was a significant increase in transcutaneous partial pressure of oxygen PtcO2 (p tO2/PaO2 (p < 0.0001), ScvO2 (p < 0.0001), urine output (p < 0.006) on increasing the MAP from 65mmHg to 85mmHg. Serum base deficit also improved (p < 0.0001). CONCLUSION: Higher MAP with norepinephrine is associated with better perfusion, oxygenation parameters in patients with established septic shock. These findings suggest that there is improvement in tissue oxygenation parameters using escalating doses of norepinephrine to achieve higher MAP without inherent adverse
基金the National Natural Science Foundation of China, No. 30270491 the Natural Science Foundation of Guangdong Province, No. 04020422 Science and Technology Plan Program of Guangdong Province, No. 2003A3020304
文摘BACKGROUND： It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells （BMSCs） can in vitro induce and differentiate into the cells possessing the properties of nerve cells. But the functions of BMSCs-derived neural stem cells（NSCs） and the differentiated neuron-like cells are still unclear. OBJECTIVE： To observe whether bone marrow-derived NSCs can secrete norepinephrine （NE） under the condition of in vitro culture, induce and differentiation, and analyze the biochemical properties of BMSCs-derived NSCs. DESIGN： A non-randomized and controlled experimental observation SETTING ： Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University MATERIALS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5- month-old healthy New Zealand white rabbits. METHODS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5 month-old healthy New Zealand white rabbits. BMSCs of rabbits were isolated and performed in vitro culture, induce and differentiation with culture medium of NSCs and differentiation-inducing factor, then identified with immunocytochemical method. Experimental grouping： ①Negative control group： L-02 hepatic cell and RPMI1640 culture medium were used. ② Background culture group： Only culture medium of NSCs as culture solution was added into BMSCs to perform culture, and 0.1 volume fraction of imported fetal bovine serum was supplemented 72 hours later. ③Differentiation inducing factor group： After culture for 72 hours, retinoic acid and glial cell line-derived neurotrophic factors were added in the culture medium of BMSCs and NSCs as corresponding inducing factors. The level of NE in each group was detected on the day of culture and 5, 7, 14 and 20 days after culture with high performance liquid chromatography （HPLC）. The procedure was conducted 3 times in each group.Standard working curve was made according to the corresponding relationship of NE concentration and peak area. The concentration of NE every 1×10^7 cells was calculated according to standard curve and cell counting. MAIN OUTCOME MEASURES ： The level of NE of cultured cells was detected with HPLC; immunocytochemistrical identification of Nestin and neuron specific nuclear protein was performed. RESULTS： ① On the 14^th day after cell culture, BMSCs turned into magnus and round cells which presented Nestin-positive antigen, then changed into neuron-like cells with long processus and presented neuron specific nuclear protein -positive antigen at the 20^th day following culture. ② The ratio of NE concentration and peak area has good linear relationship, and regression equation was Y=1.168 36＋0.000 272 8X,r=-0.998 4. Coefficient variation （CV） was 〈 5% and the recovery rate was 92.39%（ Y referred to concentration and X was peak area）.③NE was well detached within 10 minutes under the condition of this experiment. ④ NE was detected in NSCs and their culture mediums, which were cultured for 7, 14 and 20 days respectively, but no NE in BMSCs, NSCs-free culture medium and L-02 hepatic cell which were as negative control under the HPLC examination. Analysis of variance showed that the level of NE gradually increased following the elongation of culture time （P 〈 0.01 ）. No significant difference in the level of NE existed at the same time between differentiation inducing factor group and basic culture group（P 〉 0.05）. CONCLUSION ： BMSCs of rabbits can proliferate in vitro and express Nestin antigen; They can differentiate into neuron-like cells, express specific neucleoprotein of mature neurons, synthesize and secrete NE as a kind of neurotransmitter.
文摘Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.
文摘The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(NE).After synapse transmissionwas blocked by perfusion of artificial cerebrospinal fluid(ACSF)with low calcium andhigh magnesium,5 in 8 neurons were still sensitive to both 5-HT and NE.On the otherhand,3 in 5 neurons responding only to 5-HT or NA were sensitive to both 5-HT andNE after the synapse transmission blockage.In some neurons which exhibited excitatoryor inhibitory responses to 5-HT or NE alone,the responses were inversed when perfusedwith 5-HT and NE in combination.These results suggest that there may exist aninhibitory interaction between 5-HT receptors and α-adrenoceptors in NTS and that most5-HT and α-adrenoceptors coexist in the same NTS neurons.
基金supported by grants from the National Natural Science Foundation of China (No. 30670880)the Shanghai Municipal Natural Science Foundation (No. XD1402600)
文摘The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.
文摘The post-collisional Cenozoic basic volcanic rocks in NE Turkey show temporal variations in whole-rock lithophile element and highly siderophile element(HSE)systematics that are mainly associated with the nature of sub-continental lithospheric mantle(SCLM)sources and parental melt generation.So far,the traditional whole-rock lithophile geochemical data of these basic volcanic rocks have provided important constraints on the nature of SCLM sources.Integrated lithophile element and HSE geochemical data of these basic volcanic rocks also reveal the heterogeneity of the SCLM source,which is principally related to variable metasomatism resulting from previous subduction(s)and post-collisional mantle-crust interactions in an extensional setting.Lithophile element geochemical features suggest that the parental magmas have derived from metasomatized spinel-to garnet-bearing SCLM sources for Eocene and Miocene basic volcanic rocks with subduction signatures whereas originated from spinel-to garnet-bearing SCLM sources for Mio-Pliocene and Plio-Quaternary basaltic volcanic rocks without the subduction signature.Lithophile element and HSE geo-chemistry also reveal that Eocene and Miocene basic vol-canic rocks were affected by more pronounced crustal contamination than the basaltic volcanic rocks of Mio-Pliocene and Quaternary.Furthermore,the integrated lithophile element and HSE compositions of these basic volcanic rocks,together with the regional asymmetric lithospheric delamination model,reveal that the compositional variation(especially due to metasomatism)was significant temporally in the heterogeneity of the SCLM sources from which parental magmas formed during the Cenozoic era.
文摘This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of peripheral sympathetic nervous system.
