心衰患者窦性心率震荡检测及多因素影响分析

目的　观察心力衰竭患者窦性心率震荡 (HRT)现象的特征并探讨其临床意义。方法　 2 0 0 4 - 0 1～ 0 4哈尔滨医科大学第一临床医学院门诊 30例心衰患者及 30名健康对照者均接受 2 4hHolter检查 ,分别计算HRT的初始值 (TO)、HRT的斜率 (TS) ,并进行TO、TS与年龄、左室射血分数 (LVEF)、左室舒张末期内径 (LVED)、室早数目、室早前心率、联律间期、代偿间期的相关分析及不同起源室早TO、TS的组间比较。结果　心衰者与健康者HRT间存在明显差别 :心衰者TO明显高于对照者 (0 5 7± 4 71%与 - 1 5 6± 2 6 0 % ,P <0 0 2 5 ) ;心衰者TS明显低于对照者 (3 17± 2 0 3%与 9 6 4± 6 4 7,P <0 0 0 1)。TO、TS与年龄、LVEF、LVED、室早数目相关 ,与室早前心率、联律间期、代偿间期不相关 ,起源不同室早的TO、TS间无明显差异。结论　慢性心衰患者中窦性心率震荡现象明显减弱 ,由于TO、TS与LVEF、LVED相关 ,可凭借TO、TS对心衰患者进行危险分层 ,但它对预后的预测价值有待于大样本长期随访来证实。     

Dose Optimization of Chloroquine by Pharmacokinetic Modeling During Pregnancy for the Treatment of Zika Virus Infection

The insidious nature of Zika virus (ZIKV) infections can have a devastating consequence for fetal development. Recent reports have highlighted that chloroquine (CQ) is capable of inhibiting ZIKV endocytosis in brain cells. We applied pharmacokinetic modeling to develop a predictive model for CQ exposure to identify an optimal maternal/fetal dosing regimen to prevent ZIKV endocytosis in brain cells. Model validation used 13 nonpregnancy and 3 pregnancy clinical studies, and a therapeutic CQ plasma window of 0.3-2 μM was derived. Dosing regimens used in rheumatoid arthritis, systemic lupus erythematosus, and malaria were assessed for their ability to target this window. Dosing regimen identified that weekly doses used in malaria were not sufficient to reach the lower therapeutic window; however, daily doses of 150 mg achieved this therapeutic window. The impact of gestational age was further assessed and culminated in a final proposed regimen of 600 mg on day 1, 300 mg on day 2 and 3, and 150 mg thereafter until the end of trimester 2, which resulted in maintaining 65% and 94% of subjects with a trough plasma concentration above the lower therapeutic window on day 6 and at term, respectively.     

气相色谱法测定鲜竹沥中愈创木酚的含量研究

目的:通过用气相色谱测定鲜竹沥中愈创木酚的含量,作为鲜竹沥的质量考核指标。方法:采用高效毛细管气相色谱法,COL:140℃,DET:190℃,INJ:170℃,时间:20 m in。结果:在此条件下,峰面积较好,且无干扰。结论:采用气相色谱法测定鲜竹沥中愈创木酚含量的方法可行。     

Visual paired comparison performance is impaired in a patient with selective hippocampal lesions and relatively intact item recognition

In this study, we have examined visual recognition memory in a patient, YR, with discrete hippocampal damage who has shown normal or nearly normal item recognition over a large number of tests. We directly compared her performance as measured using a visual paired comparison task (VPC) with her performance on delayed matching to sample (DMS) tasks. We also investigated the effect of retention interval between familiarisation and test. YR shows good visual recognition with the DMS task up to 10 s after the familiarisation period, but only shows recognition with the VPC task for the shortest retention interval (0 s). Our results are consistent with the view that hippocampal damage disrupts recollection and recall, but not item familiarity memory.     

长春瑞滨磷脂复合物的制备及其性质研究

目的 制备长春瑞滨磷脂复合物,提高药物的脂溶性,以期进一步制备长春瑞滨微粒载药系统。方法 采用溶剂挥发法制备长春瑞滨磷脂复合物,以复合率为评价指标进行单因素优化试验。采用差示扫描量热法、X射线衍射法、紫外分光光度法对复合物进行鉴别,并考察复合物的体外溶解性质变化。结果 优化条件下制备的磷脂复合物复合率为89.3%～93.7%;差示扫描量热法、X射线衍射法、紫外分光光度法验证了复合物的形成;形成磷脂复合物后,长春瑞滨的脂溶性显著提高。结论 制备的长春瑞滨磷脂复合物能显著增加药物的脂溶性,为进一步制备长春瑞滨微粒载药系统奠定基础。     

Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia

Background

Ganglionated plexi (GP) ablation has been shown to play an important role in atrial fibrillation (AF) initiation and maintenance. Also, GP ablation increases chances for prevention of AF recurrence. This study investigated the effects of GP ablation on ventricular electrophysiological properties in normal dog hearts and after acute myocardial ischemia (AMI).

Methods

Fifty anesthetized dogs were assigned into normal heart group (n = 16) and AMI heart group (n = 34). Ventricular dynamic restitution, effective refractory period (ERP), electrical alternans and ventricular fibrillation threshold (VFT) were measured before and after GP ablation in the normal heart group. In the AMI heart group, the incidence of ventricular arrhythmias and VFT were determined.

Results

In the normal heart group, GP ablation significantly prolonged ERP, facilitated electrical alternans but did not increase ERP dispersion, the slope of restitution curves and its spatial dispersion. Also, GP ablation did not cause significant change of VFT. In the AMI heart group, the incidence of ventricular arrhythmias after GP ablation was significantly higher than that in the control group or the GP plus stellate ganglion (SG) ablation group (P < 0.05). Spontaneous VF occurred in 8/12, 1/10 and 2/12 dogs in the GP ablation group, the GP plus SG ablation group and the control group, respectively (P < 0.05). VFT in the GP ablation group showed a decreased trend though a significant difference was not achieved compared with the control or the GP plus SG ablation group.

Conclusions

GP ablation increases the risk of ventricular arrhythmias in the AMI heart compared to the normal heart.     

Somatosensory systems and the milk-ejection reflex in the rat. I. Lesions of the mesencephalic lateral tegmentum disrupt the reflex and damage mesencephalic somatosensory connections

Bilateral electrolytic lesions and unilateral tracer injections were performed in lactating rats in order to study the participation of the mesencephalic lateral tegmentum in the milk-ejection reflex. The release of oxytocin was detected as a rise in intramammary pressure during each milk ejection. In animals with lesions, the lateral part of the deep grey layers of the superior colliculus, the intercollicular area and the rostromedial portion of the external nucleus of the inferior colliculus were destroyed. The mesencephalic lateral tegmentum of animals in which the milk-ejection reflex was blocked sustained a larger damage than in rats where the frequency of the milk-ejection response was only slowed down. Solutions of True Blue, horseradish peroxidase or horseradish peroxidase coupled to wheat germ agglutinin were injected in the mesencephalic lateral tegmentum of rats with and without lesions. Retrogradely labelled cells were found in several nuclei of the somatosensory pathways: the principal sensory and spinal parts of the trigeminal complex, the cuneate and gracile nuclei, the lateral cervical nucleus and the nucleus proprius of the spinal cord. Labelled cells were also found in the ventral nucleus of the lateral lemniscus, the ventral parabrachial nucleus, the gigantocellular reticular nucleus, the lateral nucleus of the substantia nigra, the prerubral nucleus of the thalamus, the hypothalamic ventromedial nucleus, the zona incerta and in the anterior and lateral hypothalamic areas. Labelled fibres and "terminal-like" labelling were found in the anterior pretectal area, in the thalamic parafascicular nucleus, in the posterior nucleus and the ventroposterior complex, in the zona incerta and in the fields of Forel, but none were observed in the supraoptic or paraventricular nuclei. Injections made in the area of the lateral cervical nucleus and in the cuneate and gracile nuclei labelled fibres and "terminal-like" fields in the external nucleus of the inferior colliculus, the intercollicular area, the deep grey layers of the superior colliculus and in the mesencephalic lateral tegmentum. After injections in the posterior nucleus and ventroposterior complex of the thalamus, retrogradely labelled cells were found in the lateral tegmentum, the intercollicular area and the external nucleus of the inferior colliculus. These results indicate that bilateral lesioning of the mesencephalic lateral tegmentum, which disrupts the milk-ejection response, could damage somatosensory projections originating from the dorsal horn of the spinal cord, the lateral cervical nucleus, the dorsal column nuclei and the sensory and spinal trigeminal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)     

Different response patterns of several ligands at the sphingosine-1-phosphate receptor subtype 3 (S1P3)

Background and purpose:

Recently, some ligands targeting the sphingosine-1-phosphate receptor subtype 3 (S1P₃) have become available. The characterization of these compounds was mainly based on one functional read-out system, although S1P₃ receptors are known to activate different signal transduction pathways. Therefore, this study pharmacologically characterizes these compounds using different assays.

Experimental approach:

Using CHO-FlpIn cells expressing the human S1P₃ receptor the potencies and maximal effects of S1P, FTY720-P, VPC23019, VPC23153 and VPC24191 were determined in three different assays [inhibition of cAMP accumulation, elevation of intracellular calcium concentrations ([Ca²⁺]_i) and S1P₃ receptor internalization].

Key results:

All compounds tested inhibited forskolin-induced cAMP accumulation, increased [Ca²⁺]_i and induced S1P₃ receptor internalization but with different potencies and maximal effects. S1P was the most potent compound in all assays followed by FTY720-P. The VPC compounds were generally less potent than S1P and FTY720-P. Regarding the maximal effects, all compounds except VPC23153, behaved as full agonists in the cAMP accumulation assay. In the calcium assay, FTY720-P, VPC23019 and VPC24191 displayed partial and VPC23153 weak partial agonist activity, relative to S1P. Interestingly, treatment with the G_i inactivator Pertussis toxin, did not affect S1P-induced [Ca²⁺]_i elevations but inhibited those in response to the other compounds, by about 50%.

Conclusions and implications:

This study demonstrated differential response patterns at the S1P₃ receptor for a range of ligands. These differences could indicate the presence of functional selectivity at this receptor as FTY720-P and the VPC compounds seemed to signal predominantly via G_i– whereas S1P activated G_i and G_q-coupled pathways.