Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Atrial Flutter with 1:1 Atrioventricular Conduction Caused by Propafenone

We describe a case of 1:1 atrial flutter in a patient with coronary disease taking propafenone. In atrial flutter, the atrial rate is usually about 300 beciis/min with 2:1 AV conduction and a ventricular rate of 150 beats/min. Class IA antiarrhythmic drugs, especially quinidine and disopyramide, may cause 1:1 AV response because they reduce atrial rate and are vagolytic. However, propafenone is a Class IC agent and has no anticholinergic properties, and the occurrence of 1:1 AV conduction at a rate of about 250 beats/min is an important side, effect that, although uncommon, should be recognized.     

Growth cones and axon trajectories of a sensory pathway in the amphibian spinal cord

Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon-Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently.     

Second‐degree atrioventricular block (Mobitz Type I) in an adolescent with anorexia nervosa: Intrinsic or acquired conduction abnormality

Anorexia nervosa (AN) can cause both functional and structural cardiac complications, including a variety of different conduction abnormalities. This is the first case report of symptomatic diurnal second‐degree atrioventricular (AV) block (Mobitz Type I) in an adolescent with AN. We present a 12‐year‐old girl with AN, restrictor sub‐type who reported cardiac symptoms during weight gain, at the time of the initial diagnosis of AV block. Second‐degree AV block (Mobitz Type I) is discussed as a possible complication of the AN, as well as being an intrinsic conduction system disease. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009     

细胞内钙信号的变化调节血管平滑肌细胞增殖

目的探讨细胞内钙信号的变化对大鼠血管平滑肌细胞(VSMC)增殖作用的影响及其对细胞内信号转导机制的变化。方法以培养的大鼠VSMC为模型,用雷尼丁(RY)剌激VSMC内贮Ca2 释放入胞浆,用3H亮氨酸及3H胸腺嘧啶掺入量作为反应VSMC增殖的指标,加入不同的细胞内信号转导阻断剂,观察对RY效应的影响。结果与对照组相比,RY浓度依赖性地促进细胞内游离钙浓度的增高,差异显著(P<0.05或0.01)。RY剌激组蛋白核酸合成速率明显增高,与对照组相比差异显著(P<0.01);尼卡地平(Nicardipine),蛋白激酶C抑制剂(H7),钙调素激酶(CaMPK)抑制剂(W7)和丝裂素活化蛋白激酶(MAPK)抑制剂(PD98059)能明显抑制RY介导的VSMC蛋白核酸合成速率增高,与RY剌激组相比差异显著(P<0.01)。结论细胞内钙信号的变化明显促进VSMC增殖,但其效应可能通过Ca2 、PKC、MAPK来介导。钙离子拮抗剂可抑制血管平滑肌细胞增殖。     

Synaptic reorganization in the medial amygdaloid nucleus after lesion of the accessory olfactory bulb of adult rat. II. New synapse formation in the medial amygdaloid nucleus by fibers from the bed nucleus of the stria terminalis

The rearrangement of terminations from the bed nucleus of stria terminalis (BST) was examined in the medial amygdaloid nucleus (MAN) at 2 months following the lesion of the accessory olfactory bulb (AOB) using an electron microscopy and degeneration study. At 2 days following a BST lesion, the number of degenerating synapses was 0.7 ± 0.1 (mean±S.E.M.) per unit area (2500 μm² in the molecular layer, and 3/0 ± 0.3 in the cellular part. At 2 months after an AOB lesion, the degenerating synapses from the AOB had completely disappeared from the MAN. The BST was then lesioned at 2 months after the AOB lesion and, 2 days following this BST lesion, the degenerating synapses were counted in MAN. The numbers observed were 3.3 ± 0.6 per unit area in the molecular layer and 4.5 ± 0.4 in the cellular part. Therefore, the number of these degenerating synapses increased significantly within the molecular layer, though, in the cellular part the number of synapses was not significantly elevated over control. No differences in postsynaptic profiles (ratio of synapses on dendritic spine to dendritic shaft) were observed after the AOB lesion. These results indicate that the BST fibers formed new synapses in the molecular layer following the denervation of AOB fibers. The possibility of new synapse formation by other afferent fibers in addition to the AOB fibers is discussed as is the relationship between lesion induced synaptic reorganization and functional recovery after injury.     

Pain and faulty breathing: a pilot study

The purpose of this pilot study was to observe both relaxed and deep breathing patterns in a convenience sample to determine the incidence of normal versus faulty patterns of respiration. These observations were then combined with respondent answers to a survey on pain history to determine if there is any correlation between faulty breathing and musculo-skeletal pain patterns. If such a correlation can be made, then we propose that clinicians working with chronic pain patients may have improved outcomes if they address and correct faulty breathing patterns. Based on this study, it is suggested to include the evaluation and treatment of faulty respiration in the rehabilitation of chronic musculo-skeletal conditions, most notably cervical pain.     

Remote-controlled catheter ablation of accessory pathways: results from the magnetic laboratory.

AIMS: This study evaluates feasibility, safety, and efficacy of magnetic remote-controlled accessory pathway (AP) ablation. METHODS AND RESULTS: The novel magnetic navigation system (MNS) (Niobe, Stereotaxis) creates a steerable magnetic field (0.08 T) controlling the distal magnetic tip of an ablation catheter. In conjunction with a catheter advancer system (Cardiodrive, Stereotaxis) remote catheter ablation is enabled. Conventional electrophysiology study identified AP conduction in 59 patients (37 males, 36+/-14 years, 60 APs). First generation 1-magnet tip (1-M) (group I, n=18), second generation bipolar 3-magnet tip (3-M) (group II, n=27), and third generation quadripolar 3-magnet tip catheters (3-M quad.) (group III, n=14) were used for magnetic remote-controlled ablation. Successful AP ablation was achieved in 67% (group I), 85% (group II), and 92% (group III). A significant decrease of median [IQR: Q1-Q3] fluoroscopy time and dosage was observed: 21.2 [12.1-33.8] min, 1110 [395-3234] microGym2 (group I); 6.5 [4.4-15.4] min, 290 [129-489] microGym2 (group II), and 4.9 [3.4-8.0] min, 129 [74-270] microGym2 (group III). Mean procedure time (217+/-67 min; 182+/-68 min, and 172+/-90 min) significantly decreased in group III. Median number [Q1-Q3] of radiofrequency current applications in groups I, II, and III was 4 [2-9], 4 [2-6], and 2 [2-4], respectively. No complications occurred. CONCLUSION: Remote AP ablation is safe and feasible using the novel MNS. Introduction of the 3-magnet quadripolar ablation catheter significantly improved the efficacy of the procedure.     

房室结逆向传导电生理特点的观察

目的研究房室结逆向传导的电生理特点。方法分析在我院行电生理检查和／或射频消融的成年患者中电生理资料比较完整的300例患者的房室结逆传电生理特点。结果射频消融术后有161例（54％）有房室结逆传。有逆传患者的前传功能要好于无逆传的患者，对于术后存在室房逆传的患者，逆传功能均明显差于前传功能。射频消融术后有28例（17％）经房室结逆传最早激动冠状静脉窦口，其逆传功能较最早激动希氏束电图的病例相比要差，而两者的前传功能差异无统计学意义。结论射频消融术后54％的患者存在房室结逆传，可能是正常人群中室房逆传的真实反映。有室房逆传患者的房室结前传功能优于无室房逆传者，也优于其本身的逆传功能。房室结逆传冲动进入心房可能存在两条不同的通路。